bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local activation of STAT‐1 and STAT‐3 in the inflamed synovium during zymosan‐induced arthritis: Exacerbation of joint inflammation in STAT‐1 gene–knockout mice
Authors: de Hooge Alfons S. K. , van de Loo Fons A. J. , Koenders Marije I. , Bennink Miranda B. , Arntz Onno J. , Kolbe Thomas , van den Berg Wim B. 
Published: June 2004

AbstractObjectiveSTAT proteins play an important role in cytokine signaling. Some investigators have reported preferential activation of STAT‐1, and others have reported preferential activation of STAT‐3, in response to endogenous interleukin‐6 (IL‐6), in patients with rheumatoid arthritis. The present study was undertaken to investigate synovial STAT‐1 and STAT‐3 activation in an experimental animal model of arthritis.MethodsZymosan was injected intraarticularly into naive wild‐type (WT), IL‐6−/−, and STAT‐1−/− mice to induce arthritis. Western blots of synovial lysates were probed with phosphospecific antibodies to detect STAT‐1/STAT‐3 activation. Inflammation was assessed histologically. Synovial gene expression of the STAT‐induced feedback inhibitors suppressor of cytokine signaling 1 (SOCS‐1) and SOCS‐3 in WT and STAT‐1−/− mice was investigated by reverse transcriptase–polymerase chain reaction.ResultsSTAT‐3 was activated in inflamed synovium of WT mice throughout the course of disease, whereas activated STAT‐1 was observed only during the chronic phase. In IL‐6−/− mice, STAT activation was limited to STAT‐3 on day 1. Although macrophage influx was not inhibited, disease went into remission after day 7 in IL‐6−/− mice. STAT‐1 deficiency resulted in exacerbation of chronic joint inflammation and granuloma formation. In STAT‐1−/− mice, STAT‐3 activation in the inflamed joints was unaltered as compared with WT mice. However, synovial SOCS‐1, but not SOCS‐3, gene expression was markedly reduced in STAT‐1−/− mice.ConclusionThe results in the IL‐6−/− mice suggest that STAT‐3 is involved in the chronicity of ZIA. Exacerbation of arthritis in STAT‐1−/− mice suggests an opposing effect of STAT‐1, i.e., suppression of joint inflammation. The expression of SOCS‐1 could be the underlying mechanism by which STAT‐1 controls joint inflammation.
Treatment of rheumatoid arthritis with humanized anti–interleukin‐6 receptor antibody: A multicenter, double‐blind, placebo‐controlled trial
Authors: Nishimoto Norihiro , Yoshizaki Kazuyuki , Miyasaka Nobuyuki , Yamamoto Kazuhiko , Kawai Shinichi , Takeuchi Tsutomu , Hashimoto Jun , Azuma Junichi , Kishimoto Tadamitsu 
Published: June 2004

AbstractObjectiveInterleukin‐6 (IL‐6) is a pleiotropic cytokine that regulates the immune response, inflammation, and hematopoiesis. Overproduction of IL‐6 plays pathologic roles in rheumatoid arthritis (RA), and the blockade of IL‐6 may be therapeutically effective for the disease. This study was undertaken to evaluate the safety and efficacy of a humanized anti–IL‐6 receptor antibody, MRA, in patients with RA.MethodsIn a multicenter, double‐blind, placebo‐controlled trial, 164 patients with refractory RA were randomized to receive either MRA (4 mg/kg body weight or 8 mg/kg body weight) or placebo. MRA was administered intravenously every 4 weeks for a total of 3 months. The clinical responses were measured using the American College of Rheumatology (ACR) criteria.ResultsTreatment with MRA reduced disease activity in a dose‐dependent manner. At 3 months, 78% of patients in the 8‐mg group, 57% in the 4‐mg group, and 11% in the placebo group achieved at least a 20% improvement in disease activity according to the ACR criteria (an ACR20 response) (P < 0.001 for 8‐mg group versus placebo). Forty percent of patients in the 8‐mg group and 1.9% in the placebo group achieved an ACR50 response (P < 0.001). The overall incidences of adverse events were 56%, 59%, and 51% in the placebo, 4‐mg, and 8‐mg groups, respectively, and the adverse events were not dose dependent. A blood cholesterol increase was observed in 44.0% of the patients. Liver function disorders and decreases in white blood cell counts were also observed, but these were mild and transient. There was no increase in antinuclear antibodies or anti‐DNA antibodies. Anti‐MRA antibodies were detected in 2 patients.ConclusionTreatment with MRA was generally well tolerated and significantly reduced the disease activity of RA.
17β‐estradiol regulates cytokine release through modulation of CD16 expression in monocytes and monocyte‐derived macrophages
Authors: Kramer P. R. , Kramer S. F. , Guan G. 
Published: June 2004

AbstractObjectiveMacrophages release cytokines, such as tumor necrosis factor α (TNFα), interleukin‐1 (IL‐1), and IL‐6, which modulate the symptoms of rheumatoid arthritis (RA). Macrophage release of these cytokines can be modulated by estrogen. Fcγ receptor type IIIA (CD16a) is a receptor expressed on macrophages that selectively binds IgG molecules, an important rheumatoid factor in RA. Binding of CD16 by anti‐CD16 monoclonal antibodies stimulates macrophage cytokine release. We undertook this study to test the hypothesis that decreased concentrations of estrogen (17β‐estradiol) directly cause an increase in CD16 expression, resulting in increased release of proinflammatory cytokines from monocytes and/or macrophages upon receptor binding.MethodsTHP‐1 cells and female human primary monocytes and monocyte‐derived macrophages were treated with no 17β‐estradiol, physiologic levels (1 × 10−8M) of 17β‐estradiol, or 1 × 10−8M 17β‐estradiol followed by withdrawal of 17β‐estradiol. Surface expression of CD16 and CD16 messenger RNA was measured using fluorescence‐activated cell sorting (FACS) and semiquantitative reverse transcription–polymerase chain reaction, respectively. Cytokine release from 17β‐estradiol–treated or untreated monocytes was then quantitated by enzyme‐linked immunosorbent assay and FACS after crosslinking the receptor with anti‐CD16 antibodies.ResultsCD16 transcript significantly increased in macrophage‐like THP‐1 cells and in primary, peripheral blood macrophages in the absence of 17β‐estradiol, and the observed increase in message was dependent on transcription. CD16 receptor levels on CD14+, transforming growth factor β–treated primary monocytes also increased in cells deprived of 17β‐estradiol. Analysis of the cytokines released showed that CD16 crosslinking stimulated significant increases in TNFα, IL‐1β, and IL‐6 due to the absence of estrogen.ConclusionEstrogen can modulate proinflammatory cytokine release from activated monocytes and/or macrophages, in part through modulation of CD16 expression.
Correlation of polymorphic variation in the promoter region of the interleukin‐1β gene with secretion of interleukin‐1β protein
Authors: Hall Stephanie K. , Perregaux David G. , Gabel Christopher A. , Woodworth Thasia , Durham L. Kathryn , Huizinga T. W. F. , Breedveld F. C. , Seymour Albert B. 
Published: June 2004

AbstractObjectiveSignificant variation in interleukin‐1β (IL‐1β) protein secretion between subjects has been observed when using a lipopolysaccharide (LPS)/ATP–mediated ex vivo blood stimulation assay. To explore the potential relationships between genetic polymorphisms in the IL1B cytokine gene and cellular responses to inflammatory stimuli such as LPS, we investigated the hypothesis that polymorphisms within the promoter and exon 5 of the IL1B gene contribute to the observed differences in IL‐1β protein secretion.MethodsThe IL1B gene polymorphisms C−511T, T−31C, and C3954T were tested for association with LPS‐induced secretion of IL‐1β protein as measured by an ex vivo blood stimulation assay. Samples from 2 independent study populations (n = 31 and n = 25) were available for use in the ex vivo assay after consent was obtained to analyze the DNA.ResultsA specific haplotype, composed of the T allele at −511 and the C allele at −31, was significantly associated with a 2–3‐fold increase in LPS‐induced IL‐1β protein secretion. This association was observed in both of the independent study populations (P = 0.0084 and P = 0.0017).ConclusionThese data suggest that polymorphisms within the promoter region of the IL1B gene contribute to observed differences in LPS‐induced IL‐1β protein secretion.
Lymphoma in rheumatoid arthritis: The effect of methotrexate and anti–tumor necrosis factor therapy in 18,572 patients
Authors: Wolfe Frederick , Michaud Kaleb 
Published: June 2004

AbstractObjectiveThe risk of lymphoma is increased in patients with rheumatoid arthritis (RA), and spontaneous reporting suggests that methotrexate (MTX) and anti–tumor necrosis factor (anti‐TNF) therapy might be associated independently with an increased risk of lymphoma. However, data from clinical trials and clinical practice do not provide sufficient evidence concerning these issues because of small sample sizes and selected study populations. The objective of this study was to determine the rate of and standardized incidence ratio (SIR) for lymphoma in patients with RA and in RA patient subsets by treatment group. Additionally, we sought to determine predictors of lymphoma in RA.MethodsWe prospectively studied 18,572 patients with RA who were enrolled in the National Data Bank for Rheumatic Diseases (NDB). Patients were surveyed biannually, and potential lymphoma cases received detailed followup. The SEER (Survey, Epidemiology, and End Results) cancer data resource was used to derive the expected number of cases of lymphoma in a cohort that was comparable in age and sex with the RA cohort.ResultsThe overall SIR for lymphoma was 1.9 (95% confidence interval [95% CI] 1.3–2.7). The SIR for biologic use was 2.9 (95% CI 1.7–4.9) and for the use of infliximab (with or without etanercept) was 2.6 (95% CI 1.4–4.5). For etanercept, with or without infliximab, the SIR was 3.8 (95% CI 1.9–7.5). The SIR for MTX was 1.7 (95% CI 0.9–3.2), and was 1.0 (95% CI 0.4–2.5) for those not receiving MTX or biologics. Lymphoma was associated with increasing age, male sex, and education.ConclusionLymphomas are increased in RA. Although the SIR is greatest for anti‐TNF therapies, differences between therapies are slight, and confidence intervals for treatment groups overlap. The increased lymphoma rates observed with anti‐TNF therapy may reflect channeling bias, whereby patients with the highest risk of lymphoma preferentially receive anti‐TNF therapy. Current data are insufficient to establish a causal relationship between RA treatments and the development of lymphoma.
Regulation of interleukin‐18 binding protein production by blood and synovial cells from patients with rheumatoid arthritis
Authors: Kawashima Masanori , Novick Daniela , Rubinstein Menachem , Miossec Pierre 
Published: June 2004

AbstractObjectiveTo study the regulation of interleukin‐18 binding protein (IL‐18BP) production by rheumatoid arthritis (RA) or control peripheral blood mononuclear cells (PBMCs) and by RA synovial tissue cells, and to compare the levels of IL‐18BP messenger RNA (mRNA) expression in whole blood from RA patients and controls.MethodsUnstimulated or phytohemagglutinin and phorbol myristate acetate (PHA/PMA)–stimulated PBMCs from 10 RA patients and 12 healthy controls and unstimulated or PHA/PMA‐stimulated synovial tissue cells from 8 RA patients were cultured with or without IL‐12 (1 ng/ml) and IL‐18 (5 ng/ml) alone or in combination. IL‐18BP and interferon‐γ (IFNγ) levels in supernatants were measured by enzyme‐linked immunosorbent assay. Levels of IL‐18BP and IFNγ mRNA expression in whole blood samples from 22 RA patients and 12 healthy controls were determined by quantitative reverse transcriptase–polymerase chain reaction.ResultsIL‐12 decreased the basal levels of IL‐18BP production by freshly isolated RA or control PBMCs, but increased those of synovial cells or PHA/PMA‐stimulated PBMCs. IL‐18 alone had no direct effect on IL‐18BP production by PBMCs or RA synovial cells, with or without stimulation. Unstimulated whole blood samples from RA patients showed lower levels of IL‐18BP mRNA expression than those from healthy controls.ConclusionThe production of IL‐18BP in response to IL‐12 and IL‐18 was regulated differently in blood and synovial cells. The difference appears to be related to the level of cell activation.
Unmet demands for health care among patients with rheumatoid arthritis: Indications for underuse?
Authors: Jacobi Catharina E. , Rupp Ines , Boshuizen Hendriek C. , Triemstra Mattanja , Dinant Huibert J. , Van Den Bos Geertrudis A. M. 
Published: June 2004

AbstractObjectiveTo assess the prevalence of unmet health care demands among rheumatoid arthritis (RA) patients, and to determine if these unmet demands indicate underuse.MethodsA total of 679 patients with RA participated in a questionnaire survey and clinical examination. Unmet health care demands and health care use were assessed for orthopedic care, allied health care, home care, and psychosocial care. Indications for underuse were determined by comparing health outcomes of patients with unmet health care demands and of health care users.ResultsOf the 679 patients, 28.7% had an unmet demand for 1 of the 4 services: 13.4% for allied health care, 9.7% for orthopedic care, 9.4% for home care, and 6.2% for psychosocial care. Underuse of allied health care, home care and psychosocial care was observed.ConclusionUnmet demands for health care are frequent among RA patients. Most unmet demands indicate underuse. Health care professionals should therefore be more responsive to the demands of patients.
Knee adduction moment and development of chronic knee pain in elders
Authors: Amin Shreyasee , Luepongsak Niyom , McGibbon Chris A. , LaValley Michael P. , Krebs David E. , Felson David T. 
Published: June 2004

AbstractObjectiveTo determine whether the adduction moment at the knee during locomotor activity contributes to the development of future chronic knee pain.MethodsWe studied 132 community‐dwelling elders who had undergone a full kinetic and kinematic motion analysis while performing 4 different activities: standing, walking, rising from a chair, and descending stairs. We contacted the participants 3–4 years after their baseline locomotion analysis and identified those who reported no knee pain at the time of motion analysis but who subsequently developed new chronic knee pain at followup. We examined whether the development of new chronic knee pain was associated with higher peak adduction moment at the knee during activities, measured at baseline.ResultsOf the 132 elders evaluated in 1995–1996, 118 (89%) were contacted in 1999. Of the 118 contacted, 80 (mean age 75 years; 78% women) had no lower extremity prosthetic joints at baseline, no known underlying inflammatory arthritis at baseline nor followup, and no baseline knee pain. At followup, 7 had developed new chronic knee pain defined as pain or stiffness on most days of the month and with walking 2 blocks or using stairs. Compared with those who did not develop knee pain, those who did develop new chronic knee pain had higher baseline adduction moments for all activities (P = 0.01), ranging from 8% higher during chair rise to 39% higher during stair descent.ConclusionWe found that greater adduction moment at the knee during activities contributes to the development of future chronic knee pain. Our results suggest that biomechanical factors may play an important role in the pathogenesis of knee pain and should be studied further.
Normal scores for nine maneuvers of the Childhood Myositis Assessment Scale
Authors: Rennebohm Robert M. , Jones Karla , Huber Adam M. , Ballinger Susan H. , Bowyer Suzanne L. , Feldman Brian M. , Hicks Jeanne , Katona Ildy M. , Lindsley Carol B. , Miller Frederick W. , Passo Murray H. , Perez Maria D. , Reed Ann M. , Wallace Carol A. , White Patience H. , Zemel Lawrence S. , Lachenbruch Peter A. , Hayes John R. , Rider Lisa G. ,   for the Juvenile Dermatomyositis Disease Activity Collaborative Study Group
Published: June 2004

AbstractObjectiveTo document and evaluate the scores that normal, healthy children achieve when performing 9 maneuvers of the Childhood Myositis Assessment Scale (CMAS).MethodsA total of 303 healthy children, 4–9 years of age, were scored as they performed 9 CMAS maneuvers. The data were then evaluated to determine whether normal scores for some maneuvers are age and sex dependent.ResultsAll children were able to achieve maximum possible scores for the supine to prone, supine to sit, floor sit, floor rise, and chair rise maneuvers. All but 2 4‐year‐olds achieved a maximum possible score for the arm raise/duration maneuver. Performance of the head lift and sit‐up maneuvers varied significantly, depending primarily on age. Children in all age groups had less difficulty performing the leg lift than the head lift or sit‐up.ConclusionThe normative data generated by this study are of value for interpreting the serial CMAS scores of children with idiopathic inflammatory myopathies.
Quality of life of people with rheumatoid arthritis as measured by the World Health Organization Quality of Life Instrument, Short Form (WHOQOL‐BREF): Score distributions and psychometric properties
Authors: Taylor William J. , Myers Julie , Simpson Russell T. , McPherson Kathryn M. , Weatherall Mark 
Published: June 2004

AbstractObjectiveTo assess the psychometric properties, including responsiveness, of the World Health Organization Quality of Life instrument, short form (WHOQOL‐BREF) in people with rheumatoid arthritis.MethodsA sample of 142 persons with rheumatoid arthritis were randomly selected from a regional disease register and completed questionnaires by postal survey. An additional sample of 72 consecutive inpatients completed questionnaires a few days prior to admission, the day of admission, the day of discharge, and 2 weeks following discharge.ResultsTest‐retest reliability was adequate (intraclass correlation coefficient 0.71–0.91). Internal consistency was adequate except for the social relationships domain (Cronbach's alpha 0.64–0.87). Factor structure was fairly similar to that previously reported. Correlation with other measures of quality of life was supportive of concurrent validity. Indices of responsiveness were satisfactory except for the social relationships and environment domains, although there was actually no statistical difference in the area under a receiver operating characteristic plot between the WHOQOL‐BREF domains and the Health Assessment Questionnaire.ConclusionThe WHOQOL‐BREF has adequate psychometric properties in people with rheumatoid arthritis and should be considered a valid outcome measure for interventions that aim to improve quality of life for people with this disease.
Development and validation of Cedars‐Sinai Health‐Related Quality of Life in Rheumatoid Arthritis (CSHQ‐RA) short form instrument
Authors: Chiou Chiun‐Fang , Sherbourne Cathy D. , Ofman Joshua , Lee Martin , Lubeck Deborah P. , Paulus Harold E. , Weisman Michael 
Published: June 2004

AbstractObjectiveTo develop an abridged version of the 33‐item Cedars‐Sinai Health‐Related Quality of Life in Rheumatoid Arthritis instrument (CSHQ‐RA) and test the validity and reliability of the abridged instrument.MethodsItems from the original 33‐item, 5‐domain CSHQ‐RA were assessed using psychometric and regression analyses of survey responses from 274 patients with rheumatoid arthritis. Items were retained in the final instrument based on statistical analysis and evaluation by an expert panel. Test‐retest reliability, internal consistency, convergent and discriminant validity, and ceiling and floor effects were examined for the shortened CSHQ‐RA.ResultsStatistical analysis and expert assessment yielded an 11‐item instrument including questions in 4 domains. Test‐retest reliability and internal consistency were high and the instrument showed good convergent and discriminant validity.ConclusionThe abridged CSHQ‐RA short form is a valid and reliable instrument that can be used to examine the impact of RA on patients' health‐related quality of life. Prospective validation in clinical trial settings is warranted.
Short‐term corticosteroids then lamivudine and plasma exchanges to treat hepatitis B virus–related polyarteritis nodosa
Authors: Guillevin L. , Mahr A. , Cohen P. , Larroche C. , Queyrel V. , Loustaud‐Ratti V. , Imbert B. , Hausfater P. , Roudier J. , Bielefeld P. , Petitjean P. , Smadja D. ,   The French Vasculitis Study Group
Published: June 2004

AbstractObjectiveTo assess the efficacy and safety of lamivudine, an antiviral agent that strongly inhibits hepatitis B virus (HBV) DNA replication, combined with plasma exchanges after short‐term corticosteroids for HBV‐related polyartertitis nodosa (PAN).MethodsTen patients (8 men, 2 women, mean ± SD age 50.4 ± 14.4 years) with previously untreated HBV‐related PAN were included in a multicenter, prospective, observational trial. Oral prednisone (1 mg/kg/day) was given for 1 week, then tapered and withdrawn within 1 week. Then, lamivudine (100 mg/day or less in the case of renal insufficiency) was started for a maximum of 6 months. Plasma exchanges were performed simultaneously and scheduled as follows: 3/week for 3 weeks, 2/week for 2 weeks, then 1/week until hepatitis B e antigen (HBeAg) to anti‐HBe antibody (HBeAb) seroconversion was obtained or until 2–3 months of clinical recovery was sustained. The primary trial endpoint was clinical recovery from HBV‐PAN at 6 months. The secondary endpoint was loss of detectable serum HBeAg and HBV DNA, and HBeAg to HBeAb seroconversion at 9 months.ResultsOne death, attributed to catheter‐related septicemia, was recorded. At 6 months, all 9 survivors had achieved clinical recovery and by 9 months, 6 of 9 (66%) had seroconverted.ConclusionThe strategy of short‐term steroids followed by lamivudine and plasma exchanges effectively led to recovery from HBV‐PAN. Because of its oral administration and good safety profile, lamivudine should henceforth be considered the antiviral agent of choice to treat HBV‐related PAN.
Effect of knee osteoarthritis on the perception of quality of life in Venezuelan patients
Authors: Chacón José G. , González Nancy E. , Véliz Aleida , Losada Benito R. , Paul Hernando , Santiago Luís G. , Antúnez Ana , Finol Yelitza , González María E. , Granados Isabel , Maldonado Irama , Maldonado Teolinda , Marín Francisco , Zambrano Gisela , Rodríguez Martín A. 
Published: June 2004

AbstractObjectiveTo measure the perception of quality of life in Venezuelan patients with knee osteoarthritis and to identify those variables that may influence it.MethodsA multicenter, cross‐sectional study of 126 mestizo patients with knee osteoarthritis recruited from 8 rheumatology centers in Venezuela. We used a Spanish‐translated version of the Arthritis Impact Measurement Scales (AIMS), as adapted in Venezuela. One‐way analysis of variance was used to compare the AIMS mean total score among subgroups of knee pain, anatomic stage, and socioeconomic status (SES); a post‐hoc test was performed to identify significant intragroup differences. Pearson's correlation coefficient was used to examine correlations between age, body mass index (BMI), disease duration, knee pain, and AIMS score. Associations between radiologic stage, SES, and AIMS scores were examined using Spearman's rank correlation. Multiple regression analysis was used to estimate predictor factors of AIMS scores.ResultsA significant correlation was found between total AIMS scores and knee pain, age, and socioeconomic status, but not with BMI, disease duration, or anatomic stage. Patients with severe knee pain differed from those with mild and moderate pain, and the highest AIMS mean total score was seen in patients within the severe knee pain subset. Patients in the highest socioeconomic levels differed from those within lowest categories. Patients classified as being at the levels of relative and critical poverty showed the highest AIMS scores. Multiple regression analysis showed that knee pain was the only variable that exerted an independent effect on the quality of life in our patients.ConclusionThe perception of quality of life is negatively affected by increasing levels of joint pain, old age, and low socioeconomic status in Venezuelan patients with knee osteoarthritis. Our study supports the need for an early and vigorous approach to treat pain in this group of patients.