bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymerization mechanisms and curing kinetics of novel polymercaptan curing system containing epoxy/nitrogen
Authors: Lü Changli , Cui Zhanchen , Yang Bai , Su Xiaoping , Huo Chengsong , Shen Jiacong
Published: October 2002

The bis[3‐(2,3‐epoxypropylthio)phenyl]‐sulfone (BEPTPhS)/trimercaptothioethylamine (TMTEA) system has a self‐catalytic effect and can cure without any other accelerator. The curing kinetics of the BEPTPhS/TMTEA system was studied by means of the dynamic and isothermal differential scanning calorimetry method. The dynamic kinetic parameters were calculated with the aid of the Kissinger and Ozawa methods. The kinetic reaction mechanism in the isothermal reaction of BEPTPhS/TMTEA was shown to follow autocatalytic kinetics. The isothermal kinetic parameters, includingk1,k2,m, andn, from the model proposed by Kamal were determined by fitting the experimental data; a good description of the curing kinetics was obtained, although deviations were observed at low conversions. The Arrhenius kinetic analysis indicated that the activation energy decreased with the increase of the reaction conversion, which indicated a change of the reaction mechanism. The isothermal kinetic analysis and Arrhenius kinetic analysis both demonstrated that the catalytic effect of the nitrogen atom in TMTEA predominated at low conversions and the autocatalytic effect predominated at high conversions. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 000–000, 2002
Inhomogeneous deformation in welded high density polyethylene
Authors: Lu Y. , Shinozaki D. M. , Herbert S.
Published: October 2002

The effect of the thermal history on the properties of welded high density polyethylene is studied. The lamellar microstructure observed in the weld is different from that in the bulk slow cooled material. The weld has lower crystallinity and smaller lamellar size, both of which change with annealing. The differences in the microstructure between the weld and the surrounding material produce differences in the plastic properties. The low ductility of the welded samples is a direct result of the relatively low yield stress within the weld. Annealing of the weld can improve the tensile properties, but in quenched welds the final properties are still inferior to the bulk material. Displacement controlled, constant velocity microindentation tests are shown to provide a rapid means of evaluating the properties of the weld. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 43–52, 2002
Effect of temperature and span series surfactant on the structure of polysulfone membranes
Authors: Tsai Hui‐An , Ruaan Ruoh‐Chyu , Wang Da‐Ming , Lai Juin‐Yih
Published: October 2002

A macrovoid structure was found in polysulfone membranes formed by the wet‐inversion method using N‐methylpyrrolidinone (NMP) and water as the solvent/nonsolvent pair. The addition of Span series surfactants in the casting solution was found to inhibit the macrovoid formation. Sorbitan monooleate (Span‐80) was more effective in inhibiting macrovoids than was sorbitan monolaurate (Span‐20). The phenomenon of macrovoid suppression became more prominent at higher temperature. The cloud‐point shift might account for the temperature effect. But there was no simple explanation for the effect caused by Span‐80. The cloud‐point position, the demixing rate, and the viscosity of the casting solution were measured. None of them could explain the effect of macrovoid inhibition by the addition of Span‐80. However, the penetration test indicated that the penetration of a nonsolvent into a surfactant‐free casting solution was caused by a convective flow, but that into Span‐80 was through diffusion. It was found that the retardation of nonsolvent penetration was the major cause of macrovoid inhibition. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 166–173, 2002
Biodegradable and biocompatible nanocomposites of poly(ϵ‐caprolactone) with hydroxyapatite nanocrystals: Thermal and mechanical properties
Authors: Hao Jianyuan , Yuan Minglong , Deng Xianmo
Published: October 2002

Nanocomposites of poly(ϵ‐caprolactone) (PCL) with hydroxyapatite nanocrystals (HAP) prepared through the solvent‐cast technique were characterized by means of transmission electron microscopy (TEM), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and tensile tests. Such composites are of great importance to make bone‐like substitutes as HAP nanocrystals have similar composition, morphology, and crystal structure as natural apatite crystals. The TEM micrograph reveals the nanocrystals dispersed homogeneously in the matrix at a microscale level. The solvent‐cast samples commonly show much higher melting points and crystallinity than the melt‐quenched samples, due to a lower undercooling as well as more sufficient time to crystallize. For both cases of samples, the melting point decreases slightly with HAP content while the level of crystallinity attained by the PCL component is not hindered by the nanocrystals. Both the glass transition temperatures and the nonisothermal crystallization temperatures are composition dependent. The tensile modulus increases with increasing HAP content while the yield stress is almost invariant with composition. Theoretical prediction of the modulus based on Halpin–Tsai equations shows excellent agreement with the experimental result. By analysis of the variation in fracture stress and strain with composition, a ductile‐to‐quasi‐brittle transition is revealed to be operative for the nanocomposites, as also can be seen by SEM. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 676–683, 2002
Transcrystallinity effects in high‐density polyethylene. II. Determination of kinetics parameters
Authors: Billon N. , Henaff V. , Haudin J. M.
Published: October 2002

Transcrystallinity may occur during differential scanning calorimetry analysis at the surfaces of the samples. In such a case, measurements may be unsuitable. We propose simple methods for the determination of intrinsic crystallization data that are accurate for the polymer and for the determination of the nucleating ability of the surfaces. These methods are based on the experimental analysis of the crystallization of samples with different and calibrated thicknesses during experiments at different constant cooling rates. Analysis of thin samples allowed the characterization of transcrystallinity, whereas analysis of at least three samples of different thicknesses allowed us to determine the true crystallization kinetics of the bulk material. These two techniques were independent of each other and were successfully applied to the case of a high‐density polyethylene. The determinations were verified with simple analytical models. A further extension could be the study of the nucleating ability of different substrates. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 734–742, 2002
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

cDNAs 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

Objective

The 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.

Methods

SDF‐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.

Results

SDF‐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.

Conclusion

This 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

Objective

To 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).

Methods

Pamidronate 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.

Results

Eighty‐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).

Conclusion

Pamidronate 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

Objective

To 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.

Methods

Immunoblot 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.

Results

Apoptosis‐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.

Conclusion

The 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

Objective

To 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).

Methods

RA 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.

Results

Intent‐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.

Conclusion

The 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

Objective

To evaluate the safety and efficacy of etanercept in the treatment of adult patients with Still's disease.

Methods

Twelve 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.

Results

Ten 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.

Conclusion

In 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

Objective

To identify a new autoantigen/autoantibody population in rheumatoid arthritis (RA) sera.

Methods

Following 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.

Results

On 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.

Conclusion

Autoantibodies 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

For 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

Objective

To quantify the inflammatory cell response in rat air pouch pseudosynovial membrane during monosodium urate monohydrate (MSU) crystal–induced inflammation.

Methods

In 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.

Results

Injection 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.

Conclusion

An 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

Objective

The 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.

Methods

Clinical 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.

Results

Both 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.

Conclusion

Mucosal 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

Objective

To 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).

Methods

We 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.

Results

At 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.

Conclusion

ArFA‐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

Objective

To determine if colchicine added to nimesulide may have a beneficial effect on osteoarthritis (OA) of the knee.

Methods

Colchicine 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.

Results

The 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).

Conclusion

Among 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.
High rate of renal relapse in 71 patients with Wegener's granulomatosis under maintenance of remission with low‐dose methotrexate
Authors: Reinhold‐Keller Eva , Fink Claudia O. E. , Herlyn Karen , Gross Wolfgang L. , de Groot Kirsten
Published: October 2002

Objective

To examine the long‐term efficacy of low‐dose intravenous methotrexate (MTX) with and without concomitant glucocorticoids (GC) for remission maintenance in patients with generalized Wegener's granulomatosis (WG) in an open‐label, prospective, standardized trial.

Methods

After induction of remission by cyclophosphamide and GC, 71 patients (41 males, 30 female) with initially generalized WG received low‐dose methotrexate at 0.3 mg/kg body weight once weekly. At study‐start 55 of 71 (77.5%) patients were on low‐dose GC (mean 5.9 mg/day) which was tapered during the study. All patients underwent interdisciplinary staging at 3‐month (and later at 6‐month) intervals to assess disease activity and extent as well as side effects. End points were the first relapse or the end of study (January 2001).

Results

Within a mean followup period of 25.2 months, 26 patients (36.6%) experienced a relapse after a mean of 19.4 months. Seventeen (65.4%) of these 26 patients had terminated GC therapy at the time of relapse. There was no difference in relapse rates among patients with and without concomitant GC at study start. Relapses occurred mainly in the initially involved organ systems, preferentially in the ear, nose and throat tract in 18 of 26 patients and the kidney in 16 of 26 patients. One renal relapse presented as rapid, progressive glomerulonephritis with lethal outcome. Further, 14 relapses were accompanied by a significant rise in creatinine values. In 15/26 patients the relapse was paralleled or preceded by a significant rise of antineutrophil cytoplasmic antibody titer. Two patients ceased MTX prematurely because of persistent leukopenia.

Conclusion

Weekly MTX is a well tolerated therapy for long‐term maintenance of remission. However, one‐third of the patients relapsed during ongoing MTX treatment, irrespective of whether they were still receiving GC. Because more than half of the relapses affected the kidney, close monitoring is indispensable.
Effect of urate‐lowering therapy on the velocity of size reduction of tophi in chronic gout
Authors: Perez‐Ruiz Fernando , Calabozo Marcelo , Pijoan Jose I. , Herrero‐Beites Ana M. , Ruibal Ana
Published: October 2002

Objective

The optimal serum urate levels necessary for elimination of tissue deposits of monosodium urate in patients with chronic gout is controversial. This observational, prospective study evaluates the relationship between serum urate levels during therapy and the velocity of reduction of tophi in patients with chronic tophaceous gout.

Method

Sixty‐three patients with crystal‐confirmed tophaceous gout were treated with allopurinol, benzbromarone, or combined therapy to achieve serum uric acid levels less than the threshold for saturation of urate in tissues. The tophi targeted for evaluation during followup were the largest in diameter found during physical examination.

Results

Patients taking benzbromarone alone or combined allopurinol and benzbromarone therapy achieved faster velocity of reduction of tophi than patients taking allopurinol alone. The velocity of tophi reduction was linearly related to the mean serum urate level during therapy. The lower the serum urate levels, the faster the velocity of tophi reduction.

Conclusion

Serum urate levels should be lowered enough to promote dissolution of urate deposits in patients with tophaceous gout. Allopurinol and benzbromarone are equally effective when optimal serum urate levels are achieved during therapy. Combined therapy may be useful in patients who do not show enough reduction in serum urate levels with single‐drug therapy.
Randomized double‐blind comparison of chimeric monoclonal antibody to tumor necrosis factor α (infliximab) versus placebo in active spondylarthropathy
Authors: Van den Bosch Filip , Kruithof Elli , Baeten Dominique , Herssens Annemie , de Keyser Filip , Mielants Herman , Veys Eric M.
Published: October 2002

Objective

To confirm in a placebo‐controlled trial the safety and efficacy profile of infliximab in short‐term treatment of patients with active spondylarthropathy (SpA).

Methods

Forty patients with active SpA were randomly assigned to receive an intravenous loading dose (weeks 0, 2, and 6) of 5 mg/kg infliximab or placebo. Evaluations for efficacy and safety were performed at weeks 1, 2, 6, 8, and 12. The primary end points of this study were the improvements in patient and physician global assessments of disease activity on a 100‐mm visual analog scale.

Results

Both primary end points improved significantly in the infliximab group compared with the baseline value, with no improvement in the placebo group. As early as week 2 and sustained up to week 12, there was a highly statistically significant difference between the values for these 2 end points in the infliximab versus the placebo group. In most of the other assessments of disease activity (laboratory measures, assessments of specific peripheral and/or axial disease), significant improvements were observed in the infliximab group compared with the baseline value and compared with placebo. Minor adverse events not causing discontinuation were equally observed in both treatment groups. There was one severe drug‐related adverse event, in which a patient developed disseminated tuberculosis.

Conclusion

Tumor necrosis factor α blockade with infliximab in patients with active SpA was well tolerated and resulted in significant clinical and laboratory improvements in this short‐term, placebo‐controlled study. However, the occurrence of tuberculosis in one patient necessitates strict inclusion criteria and long‐term followup.
Duality revisited: Construction of fractional frequency distributions based on two dual Lotka laws
Authors: Egghe L. , Rao I.K. Ravichandra
Published: October 2002

Fractional frequency distributions of, for example, authors with a certain (fractional) number of papers are very irregular and, therefore, not easy to model or to explain. This article gives a first attempt to this by assuming two simple Lotka laws (with exponent 2): one for the number of authors with n papers (total count here) and one for the number of papers with n authors, n ∈ ℕ. Based on an earlier made convolution model of Egghe, interpreted and reworked now for discrete scores, we are able to produce theoretical fractional frequency distributions with only one parameter, which are in very close agreement with the practical ones as found in a large dataset produced earlier by Rao. The article also shows that (irregular) fractional frequency distributions are a consequence of Lotka's law, and are not examples of breakdowns of this famous historical law.
Bioequivalence evaluation of two brands of gliclazide 80 mg tablets (Glyzide® & Diamicron®) — in healthy human volunteers
Authors: Najib Naji , Idkaidek Nasir , Beshtawi M. , Bader Mohammed , Admour Isra' , Alam S. Mahmood , Zaman Q. , Dham Ruwayda
Published: October 2002

A randomized, two‐way, crossover, bioequivalence study in 24 fasting, healthy, male volunteers was conducted to compare two brands of gliclazide 80 mg tablets, Glyzide®(Julphar, UAE) as test and Diamicron® (Servier Industries, France) as reference product. The study was performed at the International Pharmaceutical Research Centre (IPRC), in joint venture with Speciality Hospital, Amman, Jordan. The drug was administered with 240 ml of 20% glucose solution after a 10 h overnight fasting. After dosing, serial blood samples were collected for a period of 48 h. Plasma harvested from blood was analyzed for gliclazide by validated HPLC method. Various pharmacokinetic parameters including AUC0–t, AUC0–∝, Cmax, Tmax, T1/2, and elimination rate constant were determined from plasma concentrations of both formulations. Statistical modules (ANOVA and 90% confidence intervals) were applied to AUC0–t, AUC0–∝, and Cmax for bioequivalence evaluation of the two brands which revealed no significant difference between them, and 90% CI fell within US FDA accepted bioequivalence range of 80–125%. Based on these statistical inferences, Glyzide® was judged bioequivalent to Diamicron®. Copyright © 2002 John Wiley & Sons, Ltd.
Pharmacokinetics and metabolism of a novel antifibrotic drug pirfenidone, in mice following intravenous administration
Authors: Giri Shri N. , Wang Qingjian , Xie Yan , Lango Jozsef , Morin Dexter , Margolin Solomon B. , Buckpitt Alan R.
Published: October 2002

The present study describes the pharmacokinetics and metabolism of pirfenidone (PD), a compound which has been shown to have significant antifibrotic effects in rodent models of pulmonary and cardiac fibrosis. Despite the fact that this compound is currently in phase II clinical trials, little data are available on the metabolism and disposition of this agent in rodents or humans. Radioactive PD [benzene ring 14C(U)] was administered i.v. to mice at 40 mg PD/kg body weight, and animals were killed at varying times for determination of parent compound and metabolites in various tissues. The disappearance of parent compound from the plasma followed apparent 2‐compartment elimination kinetics with a terminal elimination half‐life of 8.6 min. Cl (0.10 ml/min/g) and Vd(ss) (0.67 ml/g) indicated that PD was rapidly distributed in body water. This is consistent with the finding that peak tissue radioactivity occurred within 5 min following the i.v. administration of [14C]‐PD and that well‐perfused tissues, kidney>liver>lung have much higher levels of parent compound and metabolites than did fat. Two peaks isolated from plasma samples by HPLC yielded mass spectra that were consistent with initial oxidation to the alcohol followed by further metabolism to the carboxylic acid. The radioactivity recovered in the 24 h urine samples averaged 97% of the administered dose and none of that was associated with the parent compound. The short plasma half‐life of parent compound in mice supports the need for additional studies in humans where the compound has been shown to have clinical benefits. Copyright © 2002 John Wiley & Sons, Ltd.
A re‐examination of probability matching and rational choice
Authors: Shanks David R. , Tunney Richard J. , McCarthy John D.
Published: October 2002

In a typical probability learning task participants are presented with a repeated choice between two response alternatives, one of which has a higher payoff probability than the other. Rational choice theory requires that participants should eventually allocate all their responses to the high‐payoff alternative, but previous research has found that people fail to maximize their payoffs. Instead, it is commonly observed that people match their response probabilities to the payoff probabilities. We report three experiments on this choice anomaly using a simple probability learning task in which participants were provided with (i) large financial incentives, (ii) meaningful and regular feedback, and (iii) extensive training. In each experiment large proportions of participants adopted the optimal response strategy and all three of the factors mentioned above contributed to this. The results are supportive of rational choice theory. Copyright © 2002 John Wiley & Sons, Ltd.
Fluorescence correlation spectroscopy for the detection and study of single molecules in biology
Authors: Medina Miguel Ángel , Schwille Petra
Published: October 2002

The recent development of single molecule detection techniques has opened new horizons for the study of individual macromolecules under physiological conditions. Conformational subpopulations, internal dynamics and activity of single biomolecules, parameters that have so far been hidden in large ensemble averages, are now being unveiled. Herein, we review a particular attractive solution‐based single molecule technique, fluorescence correlation spectroscopy (FCS). This time‐averaging fluctuation analysis which is usually performed in Confocal setups combines maximum sensitivity with high statistical confidence. FCS has proven to be a very versatile and powerful tool for detection and temporal investigation of biomolecules at ultralow concentrations on surfaces, in solution, and in living cells. The introduction of dual‐color cross‐correlation and two‐photon excitation in FCS experiments is currently increasing the number of promising applications of FCS to biological research. BioEssays 24:758–764, 2002. © 2002 Wiley Periodicals, Inc.
Non‐neural adult stem cells: tools for brain repair?
Authors: Stewart Rebecca , Przyborski Stefan
Published: October 2002

Stem cells isolated from adult mammalian tissues may provide new approaches for the autologous treatment of disease and tissue repair. Although the potential of adult stem cells has received much attention, it has also recently been brought into question. This article reviews the recent work describing the ability of non‐hematopoietic stem cells derived from adult bone marrow to form neural derivatives and their potential for brain repair. Earlier transplantation experiments imply that grafted adult stem cells can differentiate into neural derivatives. Recent reports suggest, however, that such findings may be misleading and grafted cells acquiring different identities may merely be explained by their fusion with host cells and not the result of radical changes to their program of cellular differentiation. Nonetheless, in vitro studies have shown that neural development by bone‐marrow‐derived stem cells also appears possible. Understanding the molecular mechanisms that specify the neural lineage will lead to the development of tools for the targeted production of neural cell types in vitro that may ultimately provide a source of material to treat specific neurological deficits. BioEssays 24:708–713, 2002. © 2002 Wiley Periodicals, Inc.
Structural studies of starches with different water contents
Authors: Bogracheva T. Y. , Wang Y. L. , Wang T. L. , Hedley C. L.
Published: October 2002

The proportion of double helices in starches from a series of pea [rb, rug4‐b, rug3‐a, and lam‐c mutants, and the wild type (WT) parental line], potato and maize (normal and low amylose), and wheat (normal) lines, ranged from about 30–50% on a dry weight basis. In relatively dry starch powders, only about half of the double helices were in crystalline order, this proportion being higher for A‐type than for B‐type starches.Using starch from WT pea as an example, it was found that increasing water content results in an increase in total crystallinity. When the water content was raised to a level similar to that in excess water, the proportion of crystallinity was close to the proportion of double helices (DH). Measuring crystallinity in starches with a high water content is difficult using traditional methods such as x‐ray diffraction. A method was developed, therefore, for determining starch structural characteristics in excess water by measuring the enthalpy of gelatinization transition in quasi‐equilibrium differential scanning calorimetry (DSC) experiments. It is suggested that DH% = ΔHsp/ΔHDH × 100%, where ΔHsp and ΔHDH represent the specific enthalpies of gelatinisation transition, ΔHsp being measured as J/g dry starch weight and ΔHDH as J/g DH, in starch. Studies on potato and maize starches in excess water and in 0.6M KCl showed, respectively, that ΔHDH was 36.3 and 35.6 J/g for B‐type polymorphs and 33.0 and 35.0 J/g for A‐type polymorphs. For C‐type starches, such as those from pea, intermediate values of ΔHDH, related to the proportions A‐/B‐polymorphs, should be used. The type of crystallinity in starch can be determined by the shift in peak temperature for thermograms in excess water and in excess 0.6M KCl. For B‐polymorphs this shift was found to be ∼2–3°C and for A‐polymorphs ∼7–12°C. The ratio between ordered areas with both A‐ and B‐polymorphs can be determined from the enthalpies of disruption of each area. These enthalpies can be obtained by deconvolution of bimodal thermograms produced by C‐type starches in excess 0.6M KCl. This methodical approach can be applied to all starches that give a sharp gelatinisation thermogram in excess water. Using a range of methods, including DSC, it was found that starch granules from the mutant peas are constructed in a similar way to those from the WT, with B‐polymorphs in the centre and A‐polymorphs at the periphery of all granules. The proportion of A/B‐polymorphs, however, differed between the mutants. It was found that in addition to increasing the total crystallinity, increasing the water content within the granules also resulted in an increase in the proportion of B‐polymorphs. © 2002 Wiley Periodicals, Inc. Biopolymers 64: 268–281, 2002