bluuebunny/crossref_metadata_2025 huggingface dataset:
Response latencies to postural disturbances in three species of teleostean fishes
Authors: Webb Paul W.
Published: February 2004

Flow in aquatic systems is characterized by unsteadiness that creates destabilizing perturbations. Appropriate correction responses depend on response latency. The time between a disturbance induced by either removal of a flow refuge or striking various parts of the body with a narrow water jet was measured for three species, chosen as examples of modes in teleostean body/fin organization that are expected to affect stability. Creek chub Semotilus atromaculatus is representative of fusiform-bodied soft-rayed teleosts, smallmouth bass Micropterus dolomieu of fusiform-bodied spiny-rayed forms and bluegill Lepomis macrochirus of deep-bodied spiny-rayed forms. Observations were made at 23°C. Loss of refuge resulted in a surge that fish corrected by starting to swim within 129±29 ms (mean ± 2 s.e.m.) for chub, which was significantly shorter than minimal times of approximately 200 ms for bluegill and bass. Slips and heaves induced by water jets initially resulted in extension of the median and paired fins that would damp growth of the disturbance, but otherwise these disturbances were ignored. Yaws and pitches were more likely to cause fish to swim away from the stimulus, making corrections as they did so. There were no differences in latencies for slip,heave, yaw and pitch disturbances within each species, but latencies varied among species. For these disturbances, responses averaged 123±19 ms for chub, again significantly smaller than those of 201±24 ms for bass and 208±52 ms for bluegill. Values for the two centrarchids were not significantly different (P>0.08). The response latency for rolling disturbances did not differ among species but was significantly smaller than that for other disturbances, with an overall latency of 70±15 ms. The greater responsiveness to hydrostatic rolling instability is attributed to functions requiring an upright posture and differences among species in habitat preferences.
Cloacal evaporative cooling: a previously undescribed means of increasing evaporative water loss at higher temperatures in a desert ectotherm, the Gila monster Heloderma suspectum
Authors: DeNardo Dale F. , Zubal Tricia E. , Hoffman Ty C.M.
Published: February 2004

The Gila monster Heloderma suspectum is an active forager in an environment that, at times, can be extremely hot and arid. Thus, Gila monsters face extreme thermostatic and hydrostatic demands. For a desert ectotherm routinely risking dehydration, evaporative water loss (EWL) is typically viewed as detrimental. Yet evaporation simultaneously dehydrates and cools an animal. We explored EWL in Gila monsters by measuring cutaneous, ventilatory and cloacal EWL at five ambient temperatures between 20.5°C and 40°C. Our results show that Gila monsters have high EWL rates relative to body mass. Cutaneous EWL underwent a consistent, temperature-dependent increase over the entire range of test temperatures (Q10=1.61, with EWL ranging from 0.378 to 0.954 mg g–1 h–1). Ventilatory EWL did not show a significant temperature-dependent response, but ranged from 0.304 to 0.663 mg g–1 h–1. Cloacal EWL was extremely low and relatively constant between 20.5°C and 35°C, but rose dramatically above 35°C (Q10 >8.3×107,from 0.0008 at 35°C to 7.30 mg g–1 h–1at 40°C). This steep rise in cloacal EWL coincided with an increasing suppression of body temperature relative to ambient temperature. Dehydration to 80% of initial body mass led to a delay in the onset and an attenuation of the dramatic increase in cloacal EWL. These results emphasize the potential value of EWL for thermoregulation in ectotherms and demonstrate for the first time the role of the cloaca in this process.
Muscle activation and strain during suction feeding in the largemouth bassMicropterus salmoides
Authors: Carroll Andrew M.
Published: February 2004

Activation and strain in the sternohyoideus (SH) were measured in vivo in five largemouth bass Micropterus salmoides. The SH is thought to actuate lower jaw depression, hyoid depression and suspensorial abduction during suction feeding in teleost fish. Sonomicrometry was used to measure fascicle shortening and lower jaw kinematics, while activity was measured by electromyography (EMG). SH fascicles shortened by an average of 11% during suction feeding. In three fish SH fascicles consistently shortened during fast lower jaw depression, but in two individuals they contracted isometrically or lengthened slightly during fast lower jaw depression. The SH continued shortening after peak gape, presumably actuating hyoid depression and lateral expansion of the buccal cavity. Onset of SH relengthening and onset of lower jaw elevation were simultaneous, as were the return of the SH to resting length and gape closure. Activation followed the onset of shortening by an average of 23 ms, although the muscle was active an average of 15 ms before the onset of rapid shortening. SH fascicles reached sustained shortening velocities averaging –2.5 fascicle lengths per second, and generally increased shortening velocity after peak gape. The shortening velocities measured in this study suggest that the SH actively shortens to generate power during suction feeding. This study is the first direct measurement of in vivo muscle function during suction feeding, the most common mechanism of prey capture among aquatic vertebrates.
Stabilization and mobility of the head and trunk in wild monkeys during terrestrial and flat-surface walks and gallops
Authors: Dunbar Donald C. , Badam Gyani L. , Hallgrímsson Benedikt , Vieilledent Stéphane
Published: February 2004

This study investigated the patterns of rotational mobility (>20°)and stability (≤20°) of the head and trunk in wild Indian monkeys during natural locomotion on the ground and on the flat-topped surfaces of walls. Adult hanuman langurs (Semnopithecus entellus) and bonnet macaques (Macaca radiata) of either gender were cine filmed in lateral view. Whole-body horizontal linear displacement, head and trunk pitch displacement relative to space (earth horizontal), and vertical head displacement were measured from the cine films. Head-to-trunk pitch angle was calculated from the head-to-space and trunk-to-space measurements. Locomotor velocities, cycle durations, angular segmental velocities, mean segmental positions and mean peak frequencies of vertical and angular head displacements were then calculated from the displacement data. Yaw rotations were observed qualitatively. During quadrupedal walks by both species, the head was free to rotate in the pitch and yaw planes on a stabilized trunk. By contrast, during quadrupedal gallops by both species, the trunk pitched on a stabilized head. During both gaits in both species, head and trunk pitch rotations were symmetrical about comparable mean positions in both gaits, with mean head position aligning the horizontal semicircular canals near earth horizontal. Head pitch direction countered head vertical displacement direction to varying degrees during walks and only intermittently during gallops, providing evidence that correctional head pitch rotations are not essential for gaze stabilization. Head-to-space pitch velocities were below 350 deg. s–1, the threshold above which, at least among humans, the vestibulo-ocular reflex (VOR) becomes saturated. Mean peak frequencies of vertical translations and pitch rotations of the head ranged from 1 Hz to 2 Hz, a lower frequency range than that in which inertia is predicted to be the major stabilizer of the head in these species. Some variables, which were common to both walks and gallops in both species, are likely to reflect constraints in sensorimotor control. Other variables, which differed between the two gaits in both species, are likely to reflect kinematic differences,whereas variables that differed between the two species are attributed primarily to morphological and behavioural differences. It is concluded that either the head or the trunk can provide the nervous system with a reference frame for spatial orientation and that the segment providing that reference can change, depending upon the kinematic characteristics of the chosen gait.
Identifiable neurons inhibited by Earth-strength magnetic stimuli in the molluscTritonia diomedea
Authors: Wang John H. , Cain Shaun D. , Lohmann Kenneth J.
Published: February 2004

Diverse animals use the Earth's magnetic field as an orientation cue, but little is known about the sensory, processing and motor elements of the neural circuitry underlying magnetic orientation behavior. The marine mollusc Tritonia diomedea has both a magnetic compass sense and a simple nervous system accessible to electrophysiological analysis. Previous studies have revealed that four identifiable neurons, known as LPd5, RPd5, LPd6 and RPd6, respond with enhanced electrical activity to changes in Earth-strength magnetic fields. Here we report that two additional neurons, LPd7 and RPd7,are inhibited by magnetic stimuli. Cobalt fills of the Pd7 neurons indicated that two prominent neurites emerge from the soma and project to the periphery through the ipsilateral cerebral nerves CeN6 and CeN3; in some cases, a third neurite was visible in CeN2. The nerves extend to the anterior region of the animal where they innervate the lateral body walls, oral veil and mouth region. Action potentials in the Pd7 neurons propagate from the central ganglia toward the periphery. Thus, the Pd7 cells have characteristics of efferent neurons. The precise function of these cells during magnetic orientation behavior, however, remains to be determined.
Synthesis and Properties of 9,9′-Diaryl-4,5-diazafluorenes. A New Type of Electron-Transporting and Hole-Blocking Material in EL Device
Authors: Ono Katsuhiko , Yanase Tomoki , Ohkita Masakazu , Saito Katsuhiro , Matsushita Yosuke , Naka Shigeki , Okada Hiroyuki , Onnagawa Hiroyoshi
Published: February 2004

The title compounds were prepared and investigated for electron-transporting and hole-blocking materials in organic electroluminescent (EL) devices. EL efficiencies of the phosphorescent devices indicated high performance of hole-blocking ability in the compounds. A maximum external efficiency of 18% was achieved and a maximum power luminous efficiency was over 45 Lm W−1.
Surface-enhanced Infrared Spectrum of CO Adsorbed on Cu Electrodes in Solution
Authors: Miyake Hiroto , Osawa Masatoshi
Published: February 2004

A chemical deposition technique was employed for the first time in preparing thin Cu films showing extremely strong surface-enhanced infrared absorption effect for the molecules adsorbed on the surface. The enhancement was examined in an electrochemical environment by using CO as a model adsorbate. The result is compared with literature data by focusing on the band shape of the enhanced absorption.
Synthesis and Characterization of Strontium Carbonate Nanowires with a Axis Orientation and Dendritic Nanocrystals
Authors: Huang Qing , Gao Lian , Cai Ye , Aldinger Fritz
Published: February 2004

Strontium carbonate nanowires that grow along the a axis were synthesized in large scale through simple hydrothermal approach for the first time. The aspect ratio of the product is more than 1000. Dendritic nanocrystals were also generated at low temperatures. Moreover, this method is feasible to be applied in the synthesis of barium carbonate nanowires.
Detection of Hemoglobin-Based Oxygen Carriers in Human Serum for Doping Analysis: Confirmation by Size-Exclusion HPLC
Authors: Varlet-Marie Emmanuelle , Ashenden Michael , Lasne Françoise , Sicart Marie-Therese , Marion Benedicte , de Ceaurriz Jacques , Audran Michel
Published: February 2004

Background: Hemoglobin-based oxygen carriers (HBOCs) are being developed as potential substitutes for the oxygen-carrying functions of erythrocytes, but athletes may obtain and experiment with HBOCs as an illicit means of enhancing oxygen transport. An electrophoretic technique has been developed to screen for the presence of HBOCs in blood samples (Lasne et al. Clin Chem 2004;50:410–5). Interest has focused on complementary methods that can provide legally defensible scientific evidence for the presence of HBOCs in blood samples collected for doping control.

Methods: The aim of this research was to develop a size-exclusion SEC-HPLC technique to identify in plasma or serum samples the presence of HBOCs that are currently under development. This method was also used to detect a polymerized bovine hemoglobin (Hemopure®) after infusion in 12 healthy males.

Results: The chromatograms of all HBOCs tested were clearly separated from the 54-min peak associated with human hemoglobin dimers. It was possible to differentiate between the different HBOC products based solely on their chromatographic profiles, provided they were at high concentrations. Differences were discernible not only based on the presence (or absence) of peaks, but also the separation between respective peaks. The profiles for serum samples collected from the men immediately after infusion of Hemopure showed a distinctive profile. The shape of the chromatographic profile remained consistent for at least 48 h.

Conclusions: Under the analytical conditions reported here, SEC-HPLC was able to separate native hemoglobin from the modified hemoglobin molecules present in each of the HBOC products studied. In tandem with electrophoretic screening, SEC-HPLC provides evidence of the presence of HBOCs and can therefore be regarded as a method that satisfies the criteria for use in an antidoping control setting.
Inhibition of interleukin‐1β‐stimulated production of matrix metalloproteinases by hyaluronan via CD44 in human articular cartilage
Authors: Julovi Sohel M. , Yasuda Tadashi , Shimizu Makoto , Hiramitsu Teruko , Nakamura Takashi
Published: February 2004

Objective

To investigate the mechanism of the inhibitory action of hyaluronan (HA) on interleukin‐1β (IL‐1β)‐stimulated production of matrix metalloproteinases (MMPs) in human articular cartilage.

Methods

IL‐1β was added to normal and osteoarthritic (OA) human articular cartilage in explant culture to stimulate MMP production. Articular cartilage was incubated or preincubated with a clinically used form of 800‐kd HA to assess its effect on IL‐1β‐induced MMPs. Levels of secreted MMPs 1, 3, and 13 in conditioned media were detected by immunoblotting; intracellular MMP synthesis in chondrocytes was evaluated by immunofluorescence microscopy. Penetration of HA into cartilage tissue and its binding to CD44 were analyzed by fluorescence microscopy using fluoresceinated HA. Blocking experiments with anti‐CD44 antibody were performed to investigate the mechanism of action of HA.

Results

Treatment and pretreatment with 800‐kd HA at 1 mg/ml resulted in significant suppression of IL‐1β‐stimulated production of MMPs 1, 3, and 13 in normal and OA cartilage explant culture. Fluorescence histocytochemistry revealed that HA penetrated cartilage tissue and localized in the pericellular matrix around chondrocytes. HA‐binding blocking experiments using anti‐CD44 antibody demonstrated that the association of HA with chondrocytes was mediated by CD44. Preincubation with anti‐CD44 antibody, which suppressed IL‐1β‐stimulated MMPs, reversed the inhibitory effect of HA on MMP production that was induced by IL‐1β in normal and OA cartilage.

Conclusion

This study demonstrates that HA effectively inhibits IL‐1β‐stimulated production of MMP‐1, MMP‐3, and MMP‐13, which supports the clinical use of HA in the treatment of OA. The action of HA on IL‐1β may involve direct interaction between HA and CD44 on chondrocytes.
Impact of shared epitope genotype and ethnicity on erosive disease: A meta‐analysis of 3,240 rheumatoid arthritis patients
Authors: Gorman Jennifer D. , Lum Raymond F. , Chen John J. , Suarez‐Almazor Maria E. , Thomson Glenys , Criswell Lindsey A.
Published: February 2004

Objective

The strongest known genetic association in rheumatoid arthritis (RA) is with HLA–DRB1 alleles that share a similar amino acid sequence, termed the shared epitope (SE). Although many studies have examined the association of the SE with disease severity, the results have been inconsistent, which may reflect the relatively small sample sizes or ethnic differences. The aim of this study was to assess the association of HLA–DRB1 SE alleles and genotype with the development of bony erosions in RA by meta‐analysis.

Methods

We identified English‐language articles published between January 1, 1987 and June 1, 1999 through Medline, EMBase, and manual searches of 6 relevant journals. Included were studies in which molecular typing of HLA–DRB1 alleles was performed and in which the presence or absence of bony erosions was reported. Data were extracted from the studies, and erosions were coded as present or absent. Authors were contacted for missing information and data on individual patients.

Results

A total of 29 studies and 3,240 patients were available for analysis. The summary odds ratios (ORs), when all patients were evaluated as a single group, demonstrated a significant association of the presence of the SE (2 or 1 versus 0 SE alleles) with erosions (OR 2.0; 95% confidence interval [95% CI] 1.8–2.2), although significant heterogeneity was present (P = 0.002). Subgroup analyses demonstrated the important influence of ethnic background. For example, no association of the SE with erosions was demonstrated in Greeks (OR 0.8 [95% CI 0.2–1.5]). In contrast, there was a striking dose‐dependent relationship in southern European Caucasians and Asians, with ORs as high as 6.2 and 5.4, respectively, in patients with 2 SE alleles. Although our ability to assess the relationship between SE genotype and erosions was limited, particular importance of the DRB1*0401 SE allele was suggested in an analysis restricted to northern European Caucasians.

Conclusion

The SE is associated with the development of erosive disease in many ethnic groups; however, striking exceptions exist. These variations may be due to allele differences between populations, such as the frequency of DRB1*0401 among different ethnic groups. Further study to better understand the genetic and environmental differences between these populations may provide insight into mechanisms that influence the clinical expression of RA.
Tuberculosis infection in patients with rheumatoid arthritis and the effect of infliximab therapy
Authors: Wolfe Frederick , Michaud Kaleb , Anderson Janice , Urbansky Kathy
Published: February 2004

Objective

According to the Centers for Disease Control and Prevention, the 1999 and 2000 incidence rates for tuberculosis (TB) in the US population were 6.4 and 5.8, respectively, per 100,000 persons. Recently, reports of TB following infliximab administration have raised questions regarding the rate of TB in patients with rheumatoid arthritis (RA) generally and in those treated with infliximab in clinical practice. We undertook this study to determine the baseline rate of TB in RA prior to the introduction of infliximab and to determine the rate of TB among those currently receiving infliximab.

Methods

We surveyed patients with questionnaires, followed by detailed validation from medical records and physician reports. In study 1, we evaluated 10,782 RA patients in 1998–1999 prior to the widespread use of infliximab. In study 2, we evaluated 6,460 infliximab‐treated patients in 2000–2002.

Results

In study 1, the lifetime rate of TB was 696 per 100,000 patients (95% confidence interval [95% CI] 547–872). Of these cases, 76.8% occurred prior to the onset of RA. During the period of prospective followup, 1 case of TB developed during 16,173 patient‐years of followup, yielding a rate of 6.2 cases (95% CI 1.6–34.4) per 100,000 patients. In study 2, the TB incidence rate among infliximab‐treated patients was 52.5 cases (95% CI 14.3–134.4) per 100,000 patient‐years of exposure. Three of the 4 cases occurred in patients with a history of TB exposure, and no cases occurred in persons with recent TB skin tests or prophylaxis.

Conclusion

The rate of TB is not increased in RA patients generally. Among infliximab‐treated patients, the rate is 52.5 cases (95% CI 14.3–134.4) per 100,000 patient‐years of exposure. A thorough medical history regarding TB, as well as tuberculin testing and radiographic examination (if indicated), should be an essential component of anti–tumor necrosis factor therapy.
Detection of major histocompatibility complex/human cartilage gp‐39 complexes in rheumatoid arthritis synovitis as a specific and independent histologic marker
Authors: Baeten Dominique , Steenbakkers Peter G. A. , Rijnders Antonius M. W. , Boots Annemieke M. , Veys Eric M. , De Keyser Filip
Published: February 2004

Objective

Peptide 263–275 is the immunodominant epitope of human cartilage (HC) gp‐39, a candidate autoantigen in rheumatoid arthritis (RA). We recently generated and characterized a monoclonal antibody (mAb) called 12A, which is directed against HLA–DR4/HC gp‐39263–275 complexes and inhibits specific T cell responses in vitro. The aim of the present study was to analyze whether presentation of the immunodominant epitope of HC gp‐39 by shared epitope–positive synovial dendritic cells is a specific event in the development of chronic synovial inflammation in RA.

Methods

Staining with mAb 12A was performed on synovium obtained from clinically swollen joints in 65 patients with RA and 67 non‐RA controls and from joints without clinical effusion in 9 additional patients with RA.

Results

Monoclonal antibody 12A staining was observed in the synovium of 40 of the 65 patients with RA. Histologically, expression of HC gp‐39, lymphoid aggregates, CD3, and CD1a as well as the global inflammation score were higher in mAb 12A–positive RA synovium than in mAb 12A–negative synovium, indicating a follicular synovitis in these samples. Accordingly, mAb 12A stained dendritic cells in the close vicinity of lymphoid aggregates. No mAb 12A staining was detected in synovium obtained from RA joints without effusion. Clinically, there were no correlations between mAb 12A staining and clinical or biologic parameters in RA. However, positive staining was observed in 61.5% of the inflamed RA synovial samples compared with only 3.0% of the control samples (P < 0.001). This mAb 12A staining was not related to intracellular citrullinated peptides, which are another specific histologic marker for RA.

Conclusion

Presentation by synovial dendritic cells of the immunodominant epitope of HC gp‐39, in the context of the shared epitope, is associated with characteristic histologic features of follicular synovitis and is highly specific for RA. This suggests a contribution to the autoimmune‐related tissue inflammation and provides a new and independent tool for the immunopathologic diagnosis of RA.
Once‐weekly administration of 50 mg etanercept in patients with active rheumatoid arthritis: Results of a multicenter, randomized, double‐blind, placebo‐controlled trial
Authors: Keystone Edward C. , Schiff Michael H. , Kremer Joel M. , Kafka Shelly , Lovy Michael , DeVries Todd , Burge Daniel J.
Published: February 2004

Objective

To evaluate the safety, efficacy, and pharmacokinetics of 50 mg etanercept administered subcutaneously once weekly in adult patients with active rheumatoid arthritis (RA).

Methods

Four hundred twenty RA patients were randomized to receive, in a blinded manner, the study drug for up to 16 weeks: 214 patients received 50 mg etanercept once weekly, 153 received 25 mg etanercept twice weekly, and 53 received placebo for 8 weeks followed by 25 mg etanercept twice weekly for 8 weeks. Efficacy and safety were assessed at weeks 8 and 16. Pharmacokinetic analyses were performed on serum samples from patients at selected study sites. The primary efficacy end point was achievement of the American College of Rheumatology (ACR) 20% improvement criteria (ACR20 response) at week 8.

Results

An ACR20 response was achieved at week 8 by 50% of the patients receiving 50 mg etanercept once weekly, by 49% of the patients receiving 25 mg etanercept twice weekly, and by 19% of the patients in the placebo group (P ≤ 0.0001 for each etanercept group versus placebo). Similarly, achievement of the ACR50 response was attained by 18% of patients in each of the 2 etanercept groups, compared with 6% of patients in the placebo group (P < 0.03 for each comparison). Pharmacokinetics of the 2 etanercept regimens were similar at steady state. No clinically significant differences in efficacy or safety were observed between the 2 etanercept groups.

Conclusion

Safety, efficacy, and pharmacokinetics were comparable between the 2 etanercept dosing regimens. Thus, comparable clinical outcomes are to be expected when patients are treated with etanercept administered either as 50 mg once weekly or as 25 mg twice weekly.
Vβ‐restricted T cell adherence to endothelial cells: A mechanism for superantigen‐dependent vascular injury
Authors: Brogan P. A. , Shah V. , Klein N. , Dillon M. J.
Published: February 2004

Objective

To investigate the potential for endothelial cells to operate as superantigen‐presenting cells for T cells and the potential for such an interaction to cause endothelial cell activation and injury.

Methods

Class II major histocompatibility complex (MHC)–positive human umbilical vein endothelial cells (HUVECs) were cocultured for 4 hours with purified T cells and the superantigens staphylococcal enterotoxin B (SEB) or toxic shock syndrome toxin 1 (TSST‐1). After staining with fluorescence‐conjugated monoclonal antibodies, flow cytometric analysis was performed on the HUVECs and T cells to examine Vβ‐restricted T cell adherence to the endothelial cell monolayer, Vβ‐restricted T cell activation (CD69 up‐regulation), surface expression of endothelial cell activation markers, and generation of endothelial microparticles (EMPs).

Results

Coculture of purified T cells with class II MHC–positive HUVECs and either TSST‐1 or SEB resulted in Vβ‐restricted CD69 up‐regulation by CD4 and CD8 cells (Vβ2 activation for TSST‐1; Vβ3, Vβ5.1, and Vβ12 activation for SEB). Additionally, there was CD4 and CD8 T cell Vβ‐restricted adherence to the HUVEC monolayer at 4 hours. Expression of intercellular adhesion molecule 1, E‐selectin, and vascular cell adhesion molecule 1 was up‐regulated on the class II MHC–positive HUVECs following exposure to superantigen in the presence of T cells, and there was increased EMP release from activated HUVECs, which occurred earlier and was of greater magnitude than that observed in response to tumor necrosis factor α.

Conclusion

Class II MHC–positive endothelial cells operate as competent superantigen‐presenting cells for CD4 and CD8 lymphocytes in vitro. Dual signaling between endothelial cells and T cells results in Vβ‐restricted activation and adherence to endothelial monolayers and endothelial cell activation and release of EMPs expressing inducible cell adhesion molecules. It is proposed that this mechanism could account in part for the vascular injury associated with superantigen‐mediated diseases including Kawasaki disease.
Ameliorative effects of follistatin‐related protein/TSC‐36/FSTL1 on joint inflammation in a mouse model of arthritis
Authors: Kawabata Daisuke , Tanaka Masao , Fujii Takao , Umehara Hisanori , Fujita Yoshimasa , Yoshifuji Hajime , Mimori Tsuneyo , Ozaki Shoichi
Published: February 2004

Objective

To clarify the in vivo function of follistatin‐related protein (FRP)/TSC‐36/FSTL1 in rheumatoid arthritis (RA), we investigated the roles of FRP in a mouse model of arthritis.

Methods

Arthritis was induced in BALB/c mice by injecting anti–type II collagen monoclonal antibody and lipopolysaccharide. Mice were treated with daily intraperitoneal injections of 20 μg of recombinant FRP. Development of arthritis was assessed by the clinical score and footpad swelling. Histologic examination of affected paws was performed on day 21 after the onset of arthritis. The gene expression profiles of affected paws in FRP‐treated and untreated mice were compared using commercially available complementary DNA (cDNA) arrays. The difference in gene expression was confirmed by real‐time quantitative reverse transcription–polymerase chain reaction.

Results

Treatment with recombinant FRP showed significant amelioration of the arthritis severity. Histologic analyses confirmed this finding and revealed the alleviation of cellular infiltration into the synovium as well as cartilage damage. The significant decrease in the amount of urinary deoxypyridinoline also indicated the ameliorative effect of FRP on joint destruction. Moreover, cDNA array analysis of the gene expression profile in FRP‐treated arthritic lesions revealed a reduced expression of the c‐fos, ets‐2, IL6, MMP3, and MMP9 genes, some of which are thought to be associated with synovial inflammation and joint destruction.

Conclusion

These findings from in vivo experiments suggest that FRP could be one of the key molecules in the treatment of inflammatory joint diseases such as RA.
Reliability of the knee examination in osteoarthritis: Effect of standardization
Authors: Cibere Jolanda , Bellamy Nicholas , Thorne Anona , Esdaile John M. , McGorm Kelly J. , Chalmers Andrew , Huang Simon , Peloso Paul , Shojania Kam , Singer Joel , Wong Hubert , Kopec Jacek
Published: February 2004

Objective

To assess the reliability of physical examination of the osteoarthritic (OA) knee by rheumatologists, and to evaluate the benefits of standardization.

Methods

Forty‐two physical signs and techniques were evaluated using a 6 × 6 Latin square design. Patients with mild to severe knee OA, based on physical and radiographic signs, were examined in random order prior to and following standardization of techniques. For those signs with dichotomous scales, agreement among the rheumatologists was calculated as the prevalence‐adjusted bias‐adjusted kappa (PABAK), while for the signs with continuous and ordinal scales, a reliability coefficient (Rc) was calculated using analysis of variance. A PABAK of >0.60 and an Rc of >0.80 were considered to indicate adequate reliability.

Results

Adequate poststandardization reliability was achieved for 30 of 42 physical signs/techniques (71%). The most highly reliable signs identified by physical examination of the OA knee included alignment by goniometer (Rc = 0.99), bony swelling (Rc = 0.97), general passive crepitus (Rc = 0.96), gait by inspection (PABAK = 0.78), effusion bulge sign (Rc = 0.97), quadriceps atrophy (Rc = 0.97), medial tibiofemoral tenderness (Rc = 0.94), lateral tibiofemoral tenderness (Rc = 0.85), patellofemoral tenderness by grind test (Rc = 0.94), and flexion contracture (Rc = 0.95). The standardization process resulted in substantial improvements in reliability for evaluation of a number of physical signs, although for some signs, minimal or no effect of standardization was noted. After standardization, warmth (PABAK = 0.14), medial instability at 30° flexion (PABAK = 0.02), and lateral instability at 30° flexion (PABAK = 0.34) were the only 3 signs that were highly unreliable.

Conclusion

With the exception of physical examinations for instability, a comprehensive knee examination can be performed with adequate reliability. Standardization further improves the reliability for some physical signs and techniques. The application of these findings to future OA studies will contribute to improved outcome assessments in OA.
Analysis of cartilage biomarkers in the early phases of canine experimental osteoarthritis
Authors: Matyas John R. , Atley Lynne , Ionescu Mirela , Eyre David R. , Poole A. Robin
Published: February 2004

Objective

To study 3 body fluids for changes in the levels of 5 biomarkers of cartilage metabolism during the early phases of experimental osteoarthritis (OA).

Methods

Twenty skeletally mature mixed‐breed canines underwent unilateral surgical transection of the anterior cruciate ligament. Samples of joint fluid, serum, and urine were obtained preoperatively and just before necropsy (3 weeks or 12 weeks postoperatively). Biomarkers included 2 markers of cartilage matrix synthesis/turnover (aggrecan 846 epitope and C‐propeptide of type II collagen) and 3 markers of cartilage degradation (keratan sulfate proteoglycan epitope, the collagenase‐generated cleavage epitope of type II collagen [Col2‐3/4Clong mono, or CIIC], and crosslinked peptides from the C‐telopeptide domain of type II collagen [Col2CTx]). Significant changes in the levels of these biomarkers were determined by paired analyses.

Results

Joint pathology was more severe in the 12‐week group compared with the 3‐week group. In joint fluid, due to limited volume, only Col2‐3/4Clong mono and Col2CTx were measured. Significant elevations in the levels of both of these markers were observed in experimental joints in both the 3‐week group and the 12‐week group. In serum, the level of aggrecan 846 epitope was elevated at both 3 weeks and 12 weeks, the level of Col2‐3/4Clong mono was elevated at 12 weeks, and the level of Col2CTx was elevated at both 3 weeks and 12 weeks. In urine, the level of Col2‐3/4Clong mono was elevated at 12 weeks after surgery.

Conclusion

Levels of biomarkers of intact aggrecan proteoglycan (aggrecan 846 epitope) and type II collagen degradation (Col2‐3/4Clong mono and Col2CTx) were elevated early after unilateral stifle joint injury, suggesting that these markers are sensitive and specific for early cartilage changes associated with isolated joint injury in this established model of experimental OA.
Spectrum of clinical features in Muckle‐Wells syndrome and response to anakinra
Authors: Hawkins Philip N. , Lachmann Helen J. , Aganna Ebun , McDermott Michael F.
Published: February 2004

Objective

Mutations in the NALP3/CIAS1/PYPAF1 gene are associated with the autoinflammatory diseases Muckle‐Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), and neonatal‐onset multisystem inflammatory disease (NOMID), which is also known as chronic infantile neurologic, cutaneous, articular (CINCA) syndrome. Molecular studies suggest that NALP3 is involved in the processing of interleukin‐1β (IL‐1β), prompting us to investigate whether IL‐1 blockade may be therapeutic in patients with MWS.

Methods

We reviewed the clinical features of 3 members of a family, all of whom had MWS associated with the NALP3 variant V200M (also designated V198M), and evaluated the response of their inflammatory disease to treatment with the recombinant human IL‐1 receptor antagonist anakinra. The subjects kept a diary of symptoms and underwent fortnightly clinical and laboratory assessments, including measurement of the serum amyloid A protein concentration.

Results

Each subject had fever, rashes, arthralgia, conjunctivitis, sensorineural deafness, and an intense acute‐phase response characteristic of MWS. However, additional features were identified, including exacerbation of their disease by cold and neurologic manifestations, that have hitherto been described only in FCAS and NOMID, respectively. Clinical and serologic evidence of active inflammatory disease resolved rapidly and completely during treatment with anakinra.

Conclusion

The remarkable response of MWS to anakinra suggests that IL‐1β has a fundamental role in the pathogenesis of inflammation associated with mutations in the NALP3 gene, and supports study of IL‐1 inhibition in patients with NOMID/CINCA syndrome or FCAS. The clinical features of the various syndromes associated with mutations in the NALP3 gene may overlap to a greater extent than has previously been recognized.
Association of radiographic hand osteoarthritis with radiographic knee osteoarthritis after meniscectomy
Authors: Englund M. , Paradowski P. T. , Lohmander L. S.
Published: February 2004

Objective

To evaluate the association between radiographic hand osteoarthritis (OA), a disease with marked heredity, and radiographic knee OA in patients treated with meniscectomy.

Methods

We retrospectively identified 170 patients (mean age 54 years [range 33–87 years], 23% women) who had undergone isolated meniscectomy an average of 20 years earlier (range 17–22 years). Patients with cruciate ligament injury were excluded. All subjects were examined by standardized knee and hand radiography. Individual joints were considered to have OA when displaying radiographic features corresponding to a Kellgren/Lawrence (K/L) grade ≥2. Hand OA was considered present if at least 1 of the following criteria was fulfilled: the presence of radiographic OA (K/L grade ≥2) in at least 1 interphalangeal joint in each hand symmetrically, or in at least 2 distal or proximal interphalangeal joints in the same hand in a pattern consistent with primary OA (in the same row or ray), or in the first carpometacarpal joint bilaterally. The association between radiographic hand OA and radiographic knee OA was evaluated using logistic regression.

Results

Radiographic hand OA was present in 57 patients (34%) and radiographic knee OA was identified in 105 patients (62%), within 94 index knees (55%) and 47 contralateral knees (28%). In a multivariate model, radiographic hand OA was associated with an increased likelihood of radiographic OA in the index knee (odds ratio [OR] 3.0, 95% confidence interval [95% CI] 1.2–7.5) and in the nonoperated contralateral knee (OR 3.5, 95% CI 1.0–12.2).

Conclusion

The presence of radiographic hand OA is associated with an increased frequency of radiographic knee OA after meniscectomy. This finding confirms and extends that of a single previous study showing an interaction between hereditary and environmental risk factors for OA, a common and genetically complex disease. Accordingly, the development of OA following a meniscal tear and the resulting meniscal surgery should not be regarded to be of secondary origin only.
Induction of costimulation of human CD4 T cells by tumor necrosis factor–related apoptosis‐inducing ligand: Possible role in T cell activation in systemic lupus erythematosus
Authors: Tsai Hwei‐Fang , Lai Jiann‐Jyh , Chou Ai‐Hsiang , Wang Ting‐Fang , Wu Chien‐Sheng , Hsu Ping‐Ning
Published: February 2004

Objective

Tumor necrosis factor–related apoptosis‐inducing ligand (TRAIL) has recently been shown to induce costimulation of mouse T cells in conjunction with signals from the T cell receptor. This study was undertaken to investigate TRAIL‐induced costimulation of human T cells in order to determine the role of TRAIL‐induced T cell activation in human systemic lupus erythematosus (SLE).

Methods

An in vitro T cell stimulation system with immobilized anti‐CD3 and recombinant TRAIL receptor DR4‐Fc proteins was used to activate human T cells purified from healthy individuals and from patients with SLE. The T cells were stimulated in vitro to assay their proliferation response by 3H‐thymidine incorporation, and their cytokine production by enzyme‐linked immunosorbent assay. Activation of p38 MAPK after TRAIL stimulation was detected with specific anti–phospho‐p38 MAPK monoclonal antibodies in Western blots.

Results

Enhanced T cell proliferation and increased interleukin‐2 and interferon‐γ (IFNγ) production were demonstrated in human T cells after stimulation with immobilized DR4‐Fc and anti‐CD3 in vitro. TRAIL engagement selectively activated human CD4, rather than CD8, T cells and augmented IFNγ production. Activation of p38 MAPK was detected after TRAIL‐induced T cell activation. T cells isolated from patients with SLE demonstrated a stronger response to TRAIL‐induced costimulation, in terms of proliferation and increased up‐regulation of CD25 after activation, when compared with T cells from healthy subjects.

Conclusion

TRAIL engagement induces costimulation of human CD4 T cells via a p38 MAPK–dependent pathway. The results suggest that enhanced reactivity of T cells to autoantigens as a result of TRAIL‐induced costimulation may play a role in the development of human autoimmune diseases.
A TNFR1 genotype with a protective role in familial rheumatoid arthritis
Authors: Dieudé Philippe , Osorio José , Petit‐Teixeira Elisabeth , Moreno Sarah , Garnier Sophie , Cailleau‐Moindrault Séverine , Stalens Caroline , Lasbleiz Sandra , Bardin Thomas , Prum Bernard , Cornélis François
Published: February 2004

Objective

Results of genome scans in rheumatoid arthritis (RA) have suggested that the tumor necrosis factor receptor I (TNFRI) and TNFRII loci (TNFR1 and TNFR2) are susceptibility loci. A TNFR2 polymorphism was found to be associated with familial RA. TNFR1 is mutated in TNFR‐associated periodic syndrome (TRAPS). We undertook this study to test the TNFR1 exonic polymorphism closest to the TRAPS mutations site (+36 A/G) for association with RA.

Methods

DNA samples were available from two groups of the French Caucasian population: 1) 100 families with 1 RA patient and both parents and 2) 86 RA index patients from families with at least 2 siblings with RA (affected sibpairs [ASPs]). The +36 A/G polymorphism of TNFR1 was genotyped by polymerase chain reaction–restriction fragment length polymorphism. The analysis was performed using the transmission disequilibrium test, the genotype relative risk, and a linkage‐based test previously described.

Results

A negative association between RA and the +36 A/A genotype, suggested in the first sample (P = 0.084), was demonstrated in the second (ASP RA) sample (odds ratio [OR] 0.465; P = 0.012) and confirmed by the linkage‐based test (OR 0.17; P = 0.008). The protective genotype, present in 41% of controls, was less frequent in RA patients: 33% in the first sample, 24% in the ASP RA sample, and 11% in the linkage‐derived subgroup. Distribution of both TNFR2 196 R/R and TNFR1 +36 A/A genotypes in the ASP RA sample showed that both suspected genotypes were exclusive.

Conclusion

We found evidence for an association between RA and a TNFR1 protective genotype, restricted to familial RA. Distribution of the TNFR2 196 R/R and TNFR1 +36 A/A genotypes in familial RA could suggest an interaction between TNFR1 and TNFR2 in the genetic susceptibility for RA.
Are US adults with arthritis meeting public health recommendations for physical activity?
Authors: Fontaine Kevin R. , Heo Moonseong , Bathon Joan
Published: February 2004

Objective

To estimate the prevalence of US adults with self‐reported, doctor‐diagnosed arthritis (without specifying the type of rheumatic disease) who are meeting the US Surgeon General's recommendations for physical activity.

Methods

Using population‐based survey data from the 2001 Behavioral Risk Factor Surveillance Survey, we classified respondents according to their arthritis status and their level of physical activity (i.e., physically inactive, insufficiently active, or meeting recommendations). Prevalence data were weighted to take account of the complex sampling design, and were broken down by a variety of demographic characteristics such as race, education, and body weight.

Results

Nearly one‐quarter (23%) of US adults reported having doctor‐diagnosed arthritis. Among adults with arthritis, 23.8% were physically inactive, 38% reported insufficient levels of physical activity, and 38.3% reported meeting the recommendations for physical activity. The highest prevalence of inactivity in adults with arthritis was found among those subjects with fewer than 8 years of formal education (47.6%), those with 9–11 years of education (35.5%), those who were African American (35.4%), those whose age was ≥65 years (31.1%), and those who were Hispanic (30.4%).

Conclusion

Despite the benefits of physical activity, more than 60% of adults with arthritis do not meet the physical activity recommendations. Efforts should be made to ensure that adults with arthritis are made aware of the benefits of physical activity, and that interventions are prescribed to assist these individuals in becoming more physically active.
Association of transforming growth factor β1 and tumor necrosis factor α polymorphisms with anti‐SSB/La antibody secretion in patients with primary Sjögren's syndrome
Authors: Gottenberg Jacques‐Eric , Busson Marc , Loiseau Pascale , Dourche Monique , Cohen‐Solal Julien , Lepage Virginia , Charron Dominique , Miceli Corinne , Sibilia Jean , Mariette Xavier
Published: February 2004

Objective

To determine whether cytokine gene polymorphisms of interferon‐γ (IFNγ), interleukin‐6 (IL‐6), IL‐10, tumor necrosis factor α (TNFα), and transforming growth factor β1 (TGFβ1) predispose subjects to the development of primary Sjögren's syndrome (SS).

Methods

Single‐base–exchange cytokine gene polymorphisms were analyzed in 129 French patients with primary SS who fulfilled the American–European Consensus Group criteria, as well as in 96 unrelated healthy subjects.

Results

The frequency of the TNF‐308A (TNF2) allele was significantly higher in the SS patients (26% versus 11%). This TNF2 association was restricted to patients with anti‐SSB (37% versus 11% in controls). Stratification did not reveal an independent effect of TNF2 and HLA–DRB1*03 on disease or on anti‐SSB antibody secretion. The frequency of allele C at codon 10 of TGFβ1 was strongly increased in the subgroup of patients with anti‐SSB; this allele acted synergistically with DRB1*03 to predispose patients to the secretion of anti‐SSB. The IL‐10 GCC haplotype carrier rate was significantly higher in SS patients than in controls (67% versus 48%), but the IL‐10 allele and genotype frequencies were not significantly different. No association was found between IL‐6 or IFNγ polymorphisms and primary SS.

Conclusion

TNF2 was associated with anti‐SSB antibody secretion, although this association was not independent of the association with DRB1*03. Allele C at codon 10 of TGFβ1 was found to act synergistically with DRB1*03 in predisposing patients to the secretion of anti‐SSB. These results therefore suggest that most of the known genetic predisposition to primary SS might concern the pattern of autoantibody diversification.