bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cloning, partial purification and in vivo developmental profile of expression of the juvenile hormone epoxide hydrolase of Ctenocephalides felis
Authors: Keiser Katherine C.L. , Brandt Kevin S. , Silver Gary M. , Wisnewski Nancy 
Published: October 2002

AbstractcDNAs encoding two different epoxide hydrolases (nCfEH1 and nCfEH2) were cloned from a cDNA library prepared from the wandering larval stage of the cat flea, Ctenocephalides felis. Predicted translations of the open reading frames indicated the clones encoded proteins of 464 (CfEH1) and 465 (CfEH2) amino acids. These proteins have a predicted molecular weight of 53 kDa and a putative 22 amino acid N‐terminal hydrophobic membrane anchor. The amino acid sequences are 77% identical, and both are homologous to previously isolated epoxide hydrolases from Manduca sexta, Trichoplusia ni, and Rattus norvegicus. Purification of native juvenile hormone epoxide hydrolase (JHEH) from unfed adult cat fleas generated a partially pure protein that hydrolyzed juvenile hormone III to juvenile hormone III‐diol. The amino terminal sequence of this ˜50‐kDa protein is identical to the deduced amino terminus of the protein encoded by the nCfEH1 clone. Affinity‐purified rabbit polyclonal antibodies raised against Escherichia coli–expressed HisCfEH1 recognized a ≈50‐kDa protein present in the partially purified fraction containing JHEH activity. Immunohistochemistry experiments using the same affinity‐purified rabbit polyclonal antibodies localized the epoxide hydrolase in developing oocytes, fat body, and midgut epithelium of the adult flea. The presence of JHEH in various flea life stages and tissues was assessed by Northern blot and enzymatic activity assays. JHEH mRNA expression remained relatively constant throughout the different flea larval stages and was slightly elevated in the unfed adult flea. JHEH enzymatic activity was highest in the late larval, pupal, and adult stages. In all stages and tissues examined, JHEH activity was significantly lower than juvenile hormone esterase (JHE) activity, the other enzyme responsible for JH catalysis. Arch. Insect Biochem. Physiol. 50:191–206, 2002. © 2002 Wiley‐Liss, Inc.
Stromal cell–derived factor 1 (CXCL12) induces monocyte migration into human synovium transplanted onto SCID Mice
Authors: Blades M. C. , Ingegnoli F. , Wheller S. K. , Manzo A. , Wahid S. , Panayi G. S. , Perretti M. , Pitzalis C. 
Published: October 2002

AbstractObjectiveThe mechanisms by which monocyte/macrophage cells migrate to the joint involve a series of integrated adhesion and signaling events in which chemokines and their receptors are strongly implicated. This study was undertaken to investigate the hypothesis that stromal cell–derived factor 1 (SDF‐1), a CXC chemokine (CXCL12), plays a critical role in monocyte/macrophage localization to synovium.MethodsSDF‐1 and CXC receptor 4 (CXCR4) expression in rheumatoid arthritis (RA) and osteoarthritis synovium and graft SDF‐1, tumor necrosis factor α (TNFα), and human and murine vascular markers were examined by immunohistochemistry and doubleimmunofluorescence. The functional capacity of SDF‐1 to modulate monocyte migration into joints was investigated by examining the localization of pro‐myelomonocytic U937 cells into synovial tissue transplanted into SCID mice. SDF‐1, TNFα, or saline was injected into graft sites and response determined by the number of fluorescently labeled U937 cells (injected intravenously) detected in grafts by ultraviolet microscopy.ResultsSDF‐1 and CXCR4 were highly expressed in CD68+ cells in the RA synovium. SDF‐1 induced U937 cell migration in vitro and in vivo in a dose‐dependent manner and, in vivo, SDF‐1 was more effective than TNFα. In contrast to TNFα, SDF‐1 did not induce intracellular adhesion molecule 1 in transplant microvasculature. Furthermore, intragraft injection of SDF‐1 did not up‐regulate TNFα, or vice versa.ConclusionThis study demonstrates, for the first time, that SDF‐1 is functional in vivo when injected into synovial grafts. In addition, SDF‐1 is more potent than TNFα, and its mechanisms of action appear to be autonomous. Therefore, SDF‐1 may be an important TNF‐independent molecule involved in the migration to and retention of inflammatory effector cells in the joint.
A six‐month randomized, controlled, double‐blind, dose‐response comparison of intravenous pamidronate (60 mg versus 10 mg) in the treatment of nonsteroidal antiinflammatory drug–refractory ankylosing spondylitis
Authors: Maksymowych Walter P. , Jhangri Gian S. , Fitzgerald Avril A. , LeClercq Sharon , Chiu Peter , Yan Alex , Skeith Kenneth J. , Aaron Stephen L. , Homik Joanne , Davis Paul , Sholter Dale , Russell Anthony S. 
Published: October 2002

AbstractObjectiveTo determine the safety and efficacy of intravenous (IV) pamidronate treatment in ankylosing spondylitis (AS) patients who have had a suboptimal response to nonsteroidal antiinflammatory drugs (NSAIDs).MethodsPamidronate at 60 mg was compared with pamidronate at 10 mg rather than placebo in view of the high incidence of transient arthralgias upon first IV exposure to the drug. The drug were given monthly for 6 months in a randomized double‐blind, controlled trial. The inclusion criterion was active disease (Bath AS Disease Activity Index [BASDAI] of ≥4 or morning stiffness of ≥45 minutes) despite stable NSAID therapy. The primary outcome measure was the BASDAI, and secondary outcomes included the Bath AS Functional Index (BASFI), Bath AS Global Index (BASGI), Bath AS Metrology Index (BASMI), erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP) level, and percentage of patients achieving a reduction of ≥25% in the BASDAI. Outcome assessments were done at −2, 0, 12, and 24 weeks, and analysis was by intent to treat.ResultsEighty‐four AS patients (67 men and 17 women; mean age 39.6 years and mean disease duration 15.1 years) were enrolled. Dosage groups were well matched at baseline for demographics, disease activity, and functional indices. At 6 months, the mean BASDAI had decreased by 2.22 (34.5%) in the 60‐mg group and by 0.93 (15%) in the 10‐mg group (P = 0.002). Significantly greater reductions in the 60‐mg group were also noted for the BASFI (P < 0.001), BASGI (P = 0.01), and BASMI (P = 0.03). Significantly more patients achieved a reduction of ≥25% in the BASDAI in the 60‐mg group versus the 10‐mg group (63.4% versus 30.2%; P = 0.004). Differences in ESR/CRP were not significant (NS). Withdrawals included 9 (20.9%) from the 10‐mg group and 3 (7.3%) from the 60‐mg group (P NS). Adverse events were confined to transient arthralgias/myalgias after the first IV infusion, occurring in 68.3% and 46.5% of patients in the 60‐mg and 10‐mg groups, respectively (P NS).ConclusionPamidronate has dose‐dependent therapeutic properties in AS.
Apoptotic U1–70 kd is antigenically distinct from the intact form of the U1–70‐kd molecule
Authors: Greidinger Eric L. , Foecking Mark F. , Ranatunga Sriya , Hoffman Robert W. 
Published: October 2002

AbstractObjectiveTo determine whether immune responses to an apoptotically modified form of a human lupus autoantigen can be distinguished from immune responses to the intact form of the same antigen.MethodsImmunoblot and enzyme‐linked immunosorbent assay techniques were used to test human autoimmune sera for the presence of antibodies to apoptotic forms of the U1– 70‐kd small nuclear RNP antigen, while antibody recognition of intact U1–70 kd was blocked.ResultsApoptosis‐specific U1–70‐kd antibodies were identified by immunoblot in 15 of 29 sera with antibodies to intact U1–70 kd and in 2 of 25 sera without measurable antibodies to intact U1–70 kd. Bacterially produced, purified, caspase‐cleaved U1–70 kd without additional posttranslational modifications was a target of apoptosis‐specific antibodies in 3 of 9 U1–70‐kd–positive sera tested.ConclusionThe apoptotic form of U1–70 kd displays B cell epitopes that are not displayed on the intact form of U1–70 kd. Caspase cleavage in the absence of additional posttranslational modifications is sufficient to induce the display of some of these epitopes. Immunity to apoptotically modified proteins can develop against caspase‐cleaved forms or against forms that undergo additional posttranslational modification.
Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: Results of a two‐year, randomized, double‐blind, placebo‐controlled trial
Authors: O'Dell James R. , Leff Robert , Paulsen Gail , Haire Claire , Mallek Jack , Eckhoff P. James , Fernandez Ana , Blakely Kent , Wees Steven , Stoner Julie , Hadley Stephen , Felt Jeffrey , Palmer William , Waytz Paul , Churchill Melvin , Klassen Lynell , Moore Gerald 
Published: October 2002

AbstractObjectiveTo compare the efficacy of combination therapy with methotrexate (MTX) and hydroxychloroquine (HCQ), MTX and sulfasalazine (SSZ), and MTX, HCQ, and SSZ in patients with rheumatoid arthritis (RA).MethodsRA patients (n = 171) who had not previously been treated with combinations of the study medications were randomized to receive 1 of the 3 treatment combinations in this 2‐year, double‐blind, placebo‐controlled protocol. HCQ was given at a dosage of 200 mg twice a day. The dosage of MTX was accelerated from 7.5 mg/week to 17.5 mg/week in all patients who were not in remission. Similarly, the dosage of SSZ was escalated from 500 mg twice a day to 1 gm twice a day in patients who were not in remission. The primary end point of the study was the percentage of patients who had a 20% response to therapy according to the American College of Rheumatology (ACR) criteria at 2 years.ResultsIntent‐to‐treat analysis revealed that patients receiving the triple combination responded best, with 78% achieving an ACR 20% response at 2 years, compared with 60% of those treated with MTX and HCQ (P = 0.05) and 49% of those treated with MTX and SSZ (P = 0.002). Similar trends were seen for the ACR 50% response, with 55%, 40%, and 29% of patients in the 3 treatment groups, respectively, achieving these results at 2 years (P = 0.005 for the triple combination group versus the MTX and SSZ group). All combination treatments were well‐tolerated. Fourteen patients (evenly distributed among the 3 groups) withdrew from the protocol because of symptoms that were potentially related to the study medication.ConclusionThe triple combination of MTX, SSZ, and HCQ is well‐tolerated, and its efficacy is superior to that of the double combination of MTX and SSZ and is marginally superior to that of the double combination of MTX and HCQ.
Etanercept in the treatment of adult patients with Still's disease
Authors: Husni M. Elaine , Maier Agnes L. , Mease Philip J. , Overman Steven S. , Fraser Patricia , Gravallese Ellen M. , Weinblatt Michael E. 
Published: October 2002

AbstractObjectiveTo evaluate the safety and efficacy of etanercept in the treatment of adult patients with Still's disease.MethodsTwelve adult patients who met criteria for Still's disease and had active arthritis were enrolled in a 6‐month open‐label trial of etanercept given in biweekly doses of 25 mg. The mean disease duration at study entry was 10.7 years. All patients had been treated unsuccessfully with other disease‐modifying antirheumatic drugs. Efficacy was evaluated according to American College of Rheumatology (ACR) improvement criteria, and adverse events were recorded.ResultsTen patients successfully completed the study; 2 withdrew due to disease flare. In 4 patients, the dosage of etanercept was increased from 25 mg biweekly to 25 mg 3 times per week. Seven patients met ACR 20% response criteria. Of these 7 responders, 4 met ACR 50% response criteria and 2 met ACR 70% response criteria. Among the 3 patients with systemic features of Still's disease (fever and rash), improvement in these features was seen in 1; the arthritis did not improve in any of these 3 patients. Except in the 2 patients who withdrew due to disease flare (rash, fever, and arthritis), no other significant adverse events occurred.ConclusionIn this initial study of etanercept therapy for Still's disease in the adult, this treatment resulted in improvement in the arthritis and was well tolerated. Additional trials should be performed to elucidate the effects of tumor necrosis factor inhibitors in Still's disease.
Presence of autoantibodies to the glycolytic enzyme α‐enolase in sera from patients with early rheumatoid arthritis
Authors: Saulot Vincent , Vittecoq Olivier , Charlionet Roland , Fardellone Patrice , Lange Catherine , Marvin Laure , Machour Nadine , Le Loët Xavier , Gilbert Danièle , Tron François 
Published: October 2002

AbstractObjectiveTo identify a new autoantigen/autoantibody population in rheumatoid arthritis (RA) sera.MethodsFollowing a population‐based recruitment effort, 255 patients with very early arthritis (median disease duration 4 months) were studied using different clinical, biologic, and radiologic assessments. After a followup period of 1 year, patients were classified as having RA (n = 145), non‐RA rheumatic diseases (n = 70), and undifferentiated arthritis (n = 40). Patients' sera were analyzed by one‐dimensional (1D) and 2D Western blotting. The recognized 50‐kd protein was analyzed by matrix‐assisted laser desorption ionization–time‐of‐flight (MALDI‐TOF) mass spectrometry (MS). RA serum reactivities were evaluated against the recombinant protein synthesized by an in vitro coupled transcription–translation system.ResultsOn 1D Western blots, 36 of the 145 RA sera bound to a 50‐kd polypeptide. On 2D Western blots, anti–50‐kd+ RA sera recognized a triplet of isoelectric point 6.5–7.0 and a molecular mass of 50 kd. The 3 spots of the triplet were analyzed by MALDI‐TOF MS and were shown to correspond to human α‐enolase. A goat anti‐enolase antiserum, which recognized a band comigrating with the 50‐kd antigen on 1D Western blots, gave a labeling pattern on 2D Western blots similar to that observed with anti–50‐kd+ RA sera. Among the 36 RA sera that identified α‐enolase in protein maps, only 8 recognized the recombinant (unmodified) α‐enolase. The specificity of anti–α ‐enolase antibodies for RA was 97.1%. Half of the anti–α ‐enolase–positive RA patients were negative for both rheumatoid factor and antifilaggrin antibodies. The presence of anti–α‐enolase antibodies was the greatest predictive factor of radiologic progression in the first 66 RA patients included.ConclusionAutoantibodies to α‐enolase, an enzyme of the glycolytic pathway, are present in the sera of patients with very early RA and have potential diagnostic and prognostic value for RA.
Autologous blood stem cell transplantation in refractory systemic lupus erythematosus with severe pulmonary impairment: A case report
Authors: Brunner M. , Greinix H. T. , Redlich K. , Knöbl P. , Smolen J. , Leitner G. , Derfler K. , Graninger W. , Kalhs P. , Machold K. 
Published: October 2002

AbstractFor patients with severe forms of autoimmunity, including systemic lupus erythematosus (SLE), purging autoreactive T cells from the immune repertoire by transplanting autologous hematopoietic stem cells (ASCT) is a therapeutic option. We describe an 18‐year‐old woman with SLE who had been treated with corticosteroids, azathioprine, cyclophosphamide (CYC), and immunopheresis for 4 years, during which time mechanical ventilation for lupus pneumonitis had been repeatedly required. After the patient was conditioned by administration of CYC and antithymocyte globulin, a total of 8.87 × 106 purified CD34+ cells per kg of body weight was infused. Hematopoietic regeneration was observed within 9 days. Twenty‐one months after ASCT, the patient continues to be in complete clinical remission, with no signs of SLE‐related disease activity and without any immunosuppressive medications. Her pulmonary function has returned to normal. Although a longer followup is required for assessment of the durability of response, the patient's course indicates that ASCT may be a way to reinduce tolerance in patients with SLE.
Monosodium urate monohydrate crystal–induced inflammation in vivo: Quantitative histomorphometric analysis of cellular events
Authors: Schiltz C. , Lioté F. , Prudhommeaux F. , Meunier A. , Champy R. , Callebert J. , Bardin T. 
Published: October 2002

AbstractObjectiveTo quantify the inflammatory cell response in rat air pouch pseudosynovial membrane during monosodium urate monohydrate (MSU) crystal–induced inflammation.MethodsIn the rat air‐pouch model, we used a computer‐assisted histomorphometric method to quantify cell distributions, based on cell linear densities, in histologic sections of membranes from pouches injected with MSU or saline. The volume, white blood cell (WBC) count, and histamine content of the pouch exudates were determined at several time points.ResultsInjection of 10 mg of MSU crystals into the pouch produced an acute exudate. After peaking at 24 hours, the exudate volume and WBC count decreased spontaneously over the next 3 days, simulating the self‐limited course of acute gout. Membrane thickness followed a parallel course. Membrane polymorphonuclear cell (PMN) linear densities were closely correlated with exudate WBC counts, suggesting PMN recruitment from the subintimal synovial membrane. Both monocyte/macrophage and mast cell linear densities increased in the subintimal layer 2 hours after crystal injection (P = 0.038 and P = 0.03, respectively, versus controls), whereas PMN linear densities showed 2 peaks, one at 4 hours and the other 24 hours. The exudate histamine content peaked 6 hours after crystal injection, when mast cell linear densities were minimal in the membranes, suggesting mast cell degranulation.ConclusionAn increase in monocyte/macrophage and mast cell densities in the membrane preceded the PMN influx in the pouch membrane and exudate, suggesting that mast cells may be involved in the early phase of MSU crystal–induced inflammation, at least in this rat model.
Escherichia coli heat‐labile enterotoxin B subunit prevents autoimmune arthritis through induction of regulatory CD4+ T cells
Authors: Luross Jeffrey A. , Heaton Tricia , Hirst Timothy R. , Day Michael J. , Williams Neil A. 
Published: October 2002

AbstractObjectiveThe receptor‐binding B subunit of Escherichia coli heat‐labile enterotoxin (EtxB) is a highly stable, nontoxic protein that is capable of modulating immune responses. This study was conducted to determine whether mucosal administration of EtxB can block collagen‐induced arthritis (CIA) and to investigate the mechanisms involved.MethodsClinical arthritis in DBA/1 mice was monitored following mucosal administration of EtxB on 4 occasions. The dependence of disease prevention on receptor binding by EtxB and the associated alterations to the immune response to type II collagen (CII) were assessed. Adoptive transfer experiments and lymph node cell cocultures were used to investigate the underlying mechanisms.ResultsBoth intranasal and intragastric delivery of EtxB were effective in preventing CIA; a 1‐μg dose of EtxB was protective after intranasal administration. A non–receptor‐binding mutant of EtxB failed to prevent disease. Intranasal EtxB lowered both the incidence and severity of arthritis when given either at the time of disease induction or 25 days later. EtxB markedly reduced levels of anti‐CII IgG2a antibodies and interferon‐γ (IFNγ) production while not affecting levels of IgG1, interleukin‐4 (IL‐4), or IL‐10. Disease protection could be transferred by CD4+ T cells from treated mice, an effect that was abrogated upon depletion of the CD25+ population. In addition, CD4+CD25+ T cells from treated mice were able to suppress anti‐CII IFNγ production by CII‐primed lymph node cells.ConclusionMucosal administration of EtxB can be used to prevent or treat CIA. Modulation of the anti‐CII immune response by EtxB is associated with a reduction in Th1 cell reactivity without a concomitant shift toward Th2. Instead, EtxB mediates its effects through enhancing the activity of a population of CD4+ regulatory T cells.
Detection of antibodies to deiminated recombinant rat filaggrin by enzyme‐linked immunosorbent assay: A highly effective test for the diagnosis of rheumatoid arthritis
Authors: Vincent Christian , Nogueira Leonor , Sebbag Mireille , Chapuy‐Regaud Sabine , Arnaud Michel , Letourneur Odile , Rolland Dominique , Fournié Bernard , Cantagrel Alain , Jolivet Michel , Serre Guy 
Published: October 2002

AbstractObjectiveTo assay antifilaggrin autoantibodies, we developed an enzyme‐linked immunosorbent assay (ELISA) using a “citrullinated” recombinant rat filaggrin. Our objectives were to assess its value for diagnosing rheumatoid arthritis (RA) and to compare the results with those obtained using 4 other reference methods for detection of antifilaggrin autoantibodies, including the commercially available ELISA that uses a modified “citrullinated” synthetic peptide derived from the sequence of human filaggrin (CCP‐ELISA).MethodsWe analyzed 711 sera from patients with well‐characterized rheumatic diseases, including 240 patients with RA. Antifilaggrin autoantibodies were detected by an ELISA using a recombinant rat filaggrin deiminated in vitro as immunosorbent (ArFA‐ELISA). The results considered were the differences between the optical densities obtained on deiminated and nondeiminated proteins. Antibodies to rat esophagus epithelium were detected by indirect immunofluorescence, while antibodies to human filaggrin were detected by immunoblotting and by a recently described ELISA using a deiminated recombinant human filaggrin. Finally, CCP‐ELISA was performed according to the manufacturer's recommendations.ResultsAt the titer thresholds allowing diagnostic specificities of 0.95, 0.985, and 0.99 to be reached, the diagnostic sensitivities of the ArFA‐ELISA were 0.76, 0.67, and 0.65, respectively. At these 3 thresholds, the sensitivities were significantly higher than those of the 4 other tests. Despite incomplete overlapping of the 5 tests, the high diagnostic performance of the ArFA‐ELISA allows us to propose this test to replace all the other methods for antifilaggrin autoantibody detection.ConclusionArFA‐ELISA appears to be the most efficient test among those available for the detection of antifilaggrin autoantibodies, in terms of diagnostic accuracy for RA. Its diagnostic performance in early RA and its prognostic value are currently under evaluation.
A randomized controlled trial to evaluate the slow‐acting symptom‐modifying effects of colchicine in osteoarthritis of the knee: A preliminary report
Authors: Das Siddharth K. , Ramakrishnan S. , Mishra Kavita , Srivastava Ragini , Agarwal G. G. , Singh Ragini , Sircar A. R. 
Published: October 2002

AbstractObjectiveTo determine if colchicine added to nimesulide may have a beneficial effect on osteoarthritis (OA) of the knee.MethodsColchicine 0.5 mg twice daily or placebo was added to nimesulide (a nonsteroidal antiinflammatory drug) in 36 patients with OA of the knee in a randomized, double‐blind, placebo‐controlled trial over a 5‐month period.ResultsThe 30% improvement rate at 20 weeks was higher in the colchicine group than in the control group receiving placebo, as measured by total Western Ontario and McMaster University Osteoarthritis scores (57.9% versus 23.5%) and visual analog scale for index knee pain (52.6% versus 17.6%) (primary measures of response). The significance persisted on combined analysis by Mantel‐Haenszel test (P = 0.062). Comparison of means also showed significant improvement in the colchicine group versus the control group in a multivariate analysis performed using T2 test (P = 0.0115).ConclusionAmong patients with OA of the knee, the group receiving colchicine plus nimesulide exhibited significantly greater symptomatic benefit at 20 weeks than did the control group receiving nimesulide plus placebo.