bluuebunny/crossref_metadata_2025 huggingface dataset:
WISP3‐dependent regulation of type II collagen and aggrecan production in chondrocytes
Authors: Sen Malini , Cheng Yu‐Ho , Goldring Mary B. , Lotz Martin K. , Carson Dennis A.
Published: February 2004

Objective

WISP3 (Wnt‐1–inducible secreted protein 3) is a member of the CCN (connective tissue growth factor, cysteine‐rich 61, nephroblastoma overexpressed) family of connective tissue growth factors. WISP3 mutations have been linked to progressive pseudorheumatoid dysplasia (PPRD). The present study was conducted to investigate whether WISP3 is responsible for the expression of cartilage‐specific molecules.

Methods

WISP3 expression in human cartilage was assessed by immunostaining with anti‐WISP3 antibody. The effect of WISP3 on chondrocyte‐specific gene regulation was determined by transfecting human chondrocyte lines C‐28/I2 and T/C‐28a2 with a WISP3 expression vector. Alterations in WISP3‐mediated messenger RNA and protein expression of cartilage‐specific molecules were assessed by reverse transcriptase–polymerase chain reaction and immunoblotting.

Results

Immunohistochemistry experiments demonstrated that WISP3 protein is expressed in the midzone chondrocytes of normal adult articular cartilage, in chondrocyte clusters of osteoarthritic cartilage, and in the zone of proliferating chondrocytes of fetal growth cartilage. Human chondrocyte lines C‐28/I2 and T/C‐28a2 transfected with a WISP3 expression vector produced increased amounts of the cartilage‐specific matrix molecules type II collagen and aggrecan, in part via activation of the sex‐determining region Y–type high mobility group box (SOX) family of transcription factors. In contrast, a mutant WISP3, previously found to be associated with PPRD, had impaired effects on cartilage‐specific gene expression.

Conclusion

Our experimental results suggest that WISP3 supports cartilage integrity by regulating the expression of type II collagen and aggrecan, and mutations linked with PPRD can compromise this function and produce cartilage loss.
Efficacy and safety profile of treatment with etoricoxib 120 mg once daily compared with indomethacin 50 mg three times daily in acute gout: A randomized controlled trial
Authors: Rubin Bernard R. , Burton Robert , Navarra Sandra , Antigua Joseph , Londoño John , Pryhuber Keith G. , Lund Margaret , Chen Erluo , Najarian Daryl K. , Petruschke Richard A. , Ozturk Zafer E. , Geba Gregory P.
Published: February 2004

Objective

To evaluate the efficacy and safety of etoricoxib and indomethacin in the treatment of patients with acute gout.

Methods

A randomized, double‐blind, active‐comparator study was conducted at 42 sites. A total of 189 men and women (≥18 years of age) who were experiencing an acute attack (≤48 hours) of clinically diagnosed gout were treated for 8 days with etoricoxib, 120 mg/day (n = 103), or indomethacin, 50 mg 3 times a day (n = 86). The primary efficacy end point was the patient's assessment of pain in the study joint (0–4‐point Likert scale) over days 2–5. Safety was assessed by adverse experiences (AEs) occurring during the trial.

Results

Etoricoxib demonstrated clinical efficacy comparable to that of indomethacin in terms of the patient's assessment of pain in the study joint. The difference in the mean change from baseline over days 2–5 was –0.08 (95% confidence interval –0.29, 0.13) (P = 0.46), which fell within the prespecified comparability bounds of –0.5 to 0.5. Secondary end points over the 8‐day study, including the onset of efficacy, reduction in signs of inflammation, and patient's and investigator's global assessments of response to therapy, confirmed the comparable efficacy of the two treatments. The etoricoxib‐treated patients had a numerically lower incidence of AEs (43.7%) than did the indomethacin‐treated patients (57.0%) and a significantly lower incidence of drug‐related AEs (16.5% versus 37.2%; P < 0.05).

Conclusion

Etoricoxib at a dosage of 120 mg once daily was confirmed to be an effective treatment for acute gout. Etoricoxib was comparable in efficacy to indomethacin at a dosage of 50 mg 3 times daily, and it was generally safe and well tolerated.
Specific autoantibodies precede the symptoms of rheumatoid arthritis: A study of serial measurements in blood donors
Authors: Nielen Markus M. J. , van Schaardenburg Dirkjan , Reesink Henk W. , van de Stadt Rob J. , van der Horst‐Bruinsma Irene E. , de Koning Margret H. M. T. , Habibuw Moud R. , Vandenbroucke Jan P. , Dijkmans Ben A. C.
Published: February 2004

Objective

Autoantibodies have been demonstrated in single serum samples from healthy subjects up to 10 years before they developed rheumatoid arthritis (RA). However, the time course for the development of antibodies before onset of clinical RA is unknown, nor is it known which antibody, or combinations of antibodies, might be most sensitive or specific for predicting future development of the disease. The present study was undertaken to investigate this.

Methods

Patients with RA who had been blood donors before the onset of disease symptoms were enrolled. Frozen serum samples from each donor were retrieved, together with 2 serum samples from controls matched for age, sex, and date of donation. All samples were tested for IgM rheumatoid factor (IgM‐RF) and anti–cyclic citrullinated peptide (anti‐CCP) antibodies.

Results

Seventy‐nine patients with RA (62% female; mean age at onset of symptoms 51 years) were included. A median of 13 samples (range 1–51) per patient were available; the earliest samples had been collected a median of 7.5 years (range 0.1–14.5) before the onset of symptoms. Thirty‐nine patients (49%) were positive for IgM‐RF and/or anti‐CCP on at least one occasion before the development of RA symptoms, a median of 4.5 years (range 0.1–13.8) before symptom onset. Of the 2,138 control samples, 1.1% were positive for IgM‐RF, and 0.6% were positive for anti‐CCP.

Conclusion

Approximately half of patients with RA have specific serologic abnormalities several years before the onset of symptoms. A finding of an elevated serum level of IgM‐RF or anti‐CCP in a healthy individual implies a high risk for the development of RA. We conclude that IgM‐RF and anti‐CCP testing with appropriately high specificity may assist in the early detection of RA in high‐risk populations.
Increased apoptosis in human osteoarthritic cartilage corresponds to reduced cell density and expression of caspase‐3
Authors: Sharif Mohammed , Whitehouse Anne , Sharman Patrick , Perry Mark , Adams Mike
Published: February 2004

Objective

Chondrocyte apoptosis has been described in both human and experimentally induced osteoarthritis (OA), but its importance in the etiopathogenesis of OA is uncertain. The aims of this study were to determine the rate of chondrocyte apoptosis using different methods, and to investigate the relationship between this process and cartilage cellularity, expression of proapoptotic molecules, and expression of antiapoptotic molecules in articular cartilage obtained from patients with OA and from nonarthritic controls.

Methods

We examined the extent of apoptosis in OA and nonarthritic control cartilage using expression of caspase‐3, an enzyme that mediates the final stage of cell death by apoptosis, as well as the TUNEL method. We used immunohistochemistry to analyze the expression of a panel of proapoptotic and antiapoptotic molecules that regulate apoptosis in articular cartilage, in order to determine whether the rate of apoptosis is associated with the expression of these molecules.

Results

The median (range) percentage of TUNEL‐positive chondrocytes in knee OA cartilage (n = 10 specimens), hip OA cartilage (n = 9), and control cartilage (n = 7) was 3.11 (1.67–3.67), 1.86 (1.22–2.89), and 0.39 (0.00–1.78), respectively. When all cartilage samples were pooled, apoptosis showed a strong inverse correlation with cellularity (r = −0.74, P < 0.0001). The percentage (range) of cells expressing caspase‐3 in the 3 groups was 15.70 (7.40–20.50), 15.77 (7.42–20.5), and 7.40 (5.90–8.00), respectively. One‐way analysis of variance showed that the differences between groups for both TUNEL‐positive cells and expression of caspase‐3 were statistically significant (P < 0.0001). There was a significant positive correlation between TUNEL‐positive cells and expression of caspase‐3 (r = 0.654, P< 0.01).

Conclusion

The data suggest that apoptosis is increased, on average, 2–4‐fold in OA cartilage. Considering that OA develops over many years, such an increase in the rate of apoptosis in the articular cartilage could play an important role in the disease process.
Association of autoantibodies to glucose‐6‐phosphate isomerase with extraarticular complications in rheumatoid arthritis
Authors: van Gaalen Floris A. , Toes Rene E. M. , Ditzel Henrik J. , Schaller Monica , Breedveld Ferdinand C. , Verweij Cor L. , Huizinga Tom W. J.
Published: February 2004

Objective

In the K/BxN mouse model, autoantibodies against glucose‐6‐phosphate isomerase (GPI) cause arthritis. The relevance of this model for human disease remains a subject of controversy. We set out to determine whether GPI autoantibodies occur in patients with rheumatoid arthritis (RA) and, if so, at what stage of the RA.

Methods

Using an enzyme‐linked immunosorbent assay, serum from 131 RA patients and 28 healthy controls was tested for autoantibodies against recombinant human GPI. Patients were grouped according to disease duration and presence of rheumatoid nodules, rheumatoid vasculitis, and Felty's syndrome, which are extraarticular complications of RA.

Results

Elevated levels of autoantibodies against GPI were present in 5% of patients with uncomplicated RA and 4% of controls. In RA complicated by extraarticular manifestations, anti‐GPI antibodies were observed in 18% of patients with rheumatoid nodules, 45% of patients with rheumatoid vasculitis, and 92% of patients with Felty's syndrome.

Conclusion

In patients with RA, autoantibodies to GPI are associated with the occurrence of extraarticular complications.
Cooperation between C1q and DNase I in the clearance of necrotic cell–derived chromatin
Authors: Gaipl Udo S. , Beyer Thomas D. , Heyder Petra , Kuenkele Susanne , Böttcher Andrea , Voll Reinhard E. , Kalden Joachim R. , Herrmann Martin
Published: February 2004

Objective

The efficient uptake of dying cells by phagocytes is essential to the avoidance of chronic inflammation. Some human autoimmune responses are thought to be driven by autoantigens from apoptotic or necrotic cells. We analyzed the role of C1q and DNase I in the disposal of necrotic cell–derived chromatin because deficiencies in these serum factors predispose to the development of systemic autoimmune disorders, such as systemic lupus erythematosus.

Methods

Human necrotic peripheral blood lymphocytes were incubated in cell culture medium supplemented with various sera or serum components. Chromatin degradation was monitored by measuring the residual DNA content by flow cytometry. The uptake of necrotic cell–derived nuclei was analyzed by in vitro phagocytosis assays.

Results

Reconstitution of C1q‐depleted serum with C1q strongly increased its ability to degrade necrotic cell–derived chromatin. Although C1q itself displayed no DNase activity, it strongly augmented the activity of serum DNase I. Whereas an excess of recombinant DNase I degraded chromatin in the absence of C1q, efficient uptake of the predigested material by monocyte‐derived phagocytes required the presence of C1q. These data show that C1q and DNase I cooperate in the degradation of chromatin from necrotic cells. Furthermore, C1q was found to be necessary for effective uptake of degraded chromatin by monocyte‐derived phagocytes.

Conclusion

C1q or DNase I deficiencies may precipitate autoimmunity in humans by a mechanism similar to that of other molecules that are involved in the safe, efficient, and rapid disposal of dying cells.
Minocycline is not effective in systemic sclerosis: Results of an open‐label multicenter trial
Authors: Mayes Maureen D. , O'Donnell Daniel , Rothfield Naomi F. , Csuka M. E.
Published: February 2004

Objective

To determine if minocycline therapy improved skin thickness in early, diffuse systemic sclerosis (SSc) by ≥30%, a level of improvement unlikely to occur in the natural history of the disease as determined by recent controlled trials.

Methods

Subjects with diffuse SSc of ≤5 years' duration were treated with oral minocycline for 1 year. The primary outcome measure was the modified Rodnan skin thickness score (MRSS).

Results

Of 36 subjects initially enrolled, 31 returned for at least 1 followup visit and were included in the analysis (modified intent‐to‐treat analysis). The group consisted of 23 women and 8 men, with a mean age of 51.7 years (range 26–82 years) and a mean disease duration of 23.5 months (range 6–60 months). The mean MRSS at entry was 22.7 (range 12–43), and at the final visit it was 18.6 (range 2–48). There was no statistically significant difference in the change in skin scores between the minocycline‐treated subjects and subjects previously reported in the D‐penicillamine (D‐Pen) trial. In addition, when adjusted for disease duration, a comparison of MRSS in the minocycline trial subjects (including all subjects active at each time point) and the previously reported D‐Pen trial subjects showed no difference and no treatment effect.

Fourteen subjects did not complete all 12 months of treatment; 10 of them withdrew due to disease progression. Disease duration was significantly shorter for the noncompleters than for the completers (P < 0.03).

Conclusion

The degree of change in the MRSS was similar to that expected in the natural course of this disease. Based on these data, minocycline is not an effective therapy for SSc.
Novel tumor necrosis factor α–regulated genes in rheumatoid arthritis
Authors: Zhang Huang‐Ge , Hyde Karren , Page Grier P. , Brand Jacob P. L. , Zhou Juling , Yu Shaohua , Allison David B. , Hsu Hui‐Chen , Mountz John D.
Published: February 2004

Objective

To determine novel genes regulated by tumor necrosis factor α (TNFα) signaling in primary rheumatoid arthritis synovial fibroblasts (RASFs).

Methods

Oligonucleotide microarrays were used to measure gene expression levels in 6 independent replicate samples of RASFs. RASFs were transfected for 18 hours with AdIκB–dominant negative (AdIκB‐DN) (n = 3) or with control AdTet expressing the reverse tetracycline trans‐activator (n = 3). The cells were stimulated for 3 hours with TNFα, and total RNA was prepared. Several novel parametric and nonparametric methods were used to rank genes in terms of the magnitude and significance of intergroup differences. Microarray expression differences were confirmed by real‐time quantitative reverse transcription–polymerase chain reaction. Small interfering RNA (siRNA) was used to specifically down‐modulate microarray‐identified genes to demonstrate their role in the promotion of apoptosis, proliferation, or matrix metalloproteinase (MMP) expression.

Results

Blocking of NF‐κB by AdIκB‐DN was associated with a down‐modulation of antiapoptosis genes, including BIRC‐3, and several novel genes, including GG2‐1, a TNFα‐inducible FLIP‐like gene. Other families of genes that were significantly down‐regulated by AdIκB‐DN included cytokines/chemokines (interleukin‐1β [IL‐1β], IL‐8, IL‐15, and RANTES), adhesion molecule (vascular cell adhesion molecule 1, intercellular adhesion molecule 1), and unique genes that have not previously been reported to be regulated by TNFα in RA. Inhibition of the GG2‐1 gene using the siRNA technique resulted in significantly enhanced apoptosis, decreased proliferation, and decreased production of MMP‐1 in TNFα‐stimulated RASFs.

Conclusion

These studies provide a comprehensive analysis of genes that are differentially regulated by TNFα signaling and NF‐κB nuclear translocation in RASFs and demonstrate methods for confirming the expression and functional significance of such genes.
Basic fibroblast growth factor mediates transduction of mechanical signals when articular cartilage is loaded
Authors: Vincent Tonia L. , Hermansson Monika A. , Hansen Ulrich N. , Amis Andrew A. , Saklatvala Jeremy
Published: February 2004

Objective

To determine whether the basic fibroblast growth factor (bFGF) mediates signal transduction in articular cartilage in response to mechanical loading.

Methods

Articular cartilage from porcine metacarpophalangeal or knee joints was cyclically loaded (62.5–250N) for 2 minutes in the absence or presence of a bFGF receptor inhibitor, SB 402451 (250 nM). Activation of the extracellularly regulated kinase MAP kinase ERK was measured by Western blot analysis. Changes in protein synthesis were assessed by measuring the incorporation of 35S‐Met/Cys into proteins secreted by cartilage explants or by isolated chondrocytes.

Results

Rapid activation of the ERK MAP kinase occurred when articular cartilage was loaded. This was dependent upon release of the bFGF because it was restricted by the FGF receptor inhibitor. Loaded explants were shown to release bFGF. Loading or bFGF stimulation of explants induced synthesis and secretion of tissue inhibitor of metalloproteinases 1 (TIMP‐1), which was inhibited by SB 402451.

Conclusion

Cyclical loading of articular cartilage causes bFGF‐dependent activation of ERK and synthesis of TIMP‐1.
TRAIL induces apoptosis of chondrocytes and influences the pathogenesis of experimentally induced rat osteoarthritis
Authors: Lee Sung Won , Lee Hye Jeong , Chung Won Tae , Choi Sun Mee , Rhyu Seung Hoon , Kim Duk K. , Kim Kyung Taek , Kim Ji Young , Kim Jong‐Min , Yoo Young Hyun
Published: February 2004

Objective

To investigate whether TRAIL influences the pathogenesis of osteoarthritis (OA).

Methods

A recombinant adenoviral vector system (Ad‐TRAIL) was used. Expression of TRAIL in a rat chondrocyte cell line (RCJ3.1C.18) and alterations in the expression of death and decoy receptors after Ad‐TRAIL infection were measured by Western blot assay. To explore the underlying mechanism, Western blot assays (to detect caspase 8, poly[ADP‐ribose] polymerase [PARP], and caspase 3 activation), mitochondrial membrane potential (ΔΨm) measurement, Hoechst staining, and DNA electrophoresis were conducted. Next, expression of TRAIL and death and decoy receptors was examined by immunochemistry in primary cultured chondrocytes and on cartilage obtained from rats with experimentally induced OA.

Results

Ad‐TRAIL infection induced expression of TRAIL in RCJ3.1C.18 cells, increased expression of death receptor 4 (DR4), and decreased expression of DR5 and decoy receptor 1 (DcR1). Ad‐TRAIL, at doses of 10 and 100 multiplicities of infection, decreased the viability of chondrocytes 4 days after infection. Reduction of ΔΨm, cytochrome c release, nuclear condensation, activation of caspase 3 and PARP, and DNA fragmentation proved the induction of apoptosis. Activation of caspase 8 was also observed. Ad‐TRAIL also induced apoptosis in primary cultured chondrocytes, in which alterations in expression of TRAIL and death receptors were similar to those observed in RCJ3.1C.18 cells. Cartilage obtained from rats with experimentally induced OA showed increased expression of TRAIL and DR4 and decreased expression of DR5 and DcR1 compared with control cartilage.

Conclusion

TRAIL induces chondrocyte apoptosis, and TRAIL‐induced chondrocyte apoptosis may play a role in the pathogenesis of OA.
Validation and reproducibility of ultrasonography in the detection of synovitis in the knee: A comparison with arthroscopy and clinical examination
Authors: Karim Z. , Wakefield R. J. , Quinn M. , Conaghan P. G. , Brown A. K. , Veale D. J. , Connor P. O' , Reece R. , Emery P.
Published: February 2004

Objective

Accurate detection of synovitis is important in both the diagnosis and outcome assessment of arthritis. This study was undertaken to assess the validity and reproducibility of ultrasonography (US) as a means of detecting synovitis in the knee, by comparing US findings with findings of arthroscopy and clinical examination.

Methods

Sixty consecutive patients with knee pain due to various arthritides had a clinical examination and US of their knee performed immediately prior to arthroscopy. All 3 assessments were performed by different clinicians who were blinded to the results obtained with the other modalities. US and clinical examination were compared with arthroscopically detected synovitis as the gold standard. Data from a subset of patients were used for calculating the inter‐ and intrareader reproducibility of US results, using a standard dichotomous (absence/presence of synovitis) as well as a graded (absence/grade of synovitis) scoring system.

Results

With the use of arthroscopy as the gold standard, US had a higher sensitivity (98% versus 85%), specificity (88% versus 25%), accuracy (97% versus 77%), positive predictive value (98% versus 88%), and negative predictive value (88% versus 20%) compared with clinical examination. The Cohen kappa values for inter‐ and intrareader reproducibility of US for distinguishing between presence and absence of synovitis were 0.71 and 0.85, respectively (P < 0.05 for both). The weighted kappa values for distinguishing grade of synovitis were 0.65 for inter‐ and 0.74 for intrareader reproducibility. The kappa value for intrareader reproducibility of arthroscopy results was 0.88.

Conclusion

Ultrasonography is a valid and reproducible technique for detecting synovitis in the knee, and is more accurate than clinical examination. It may be valuable as a tool in studies investigating pain, diagnosis, and treatment response in knee arthritis.
PM–Scl‐75 is the main autoantigen in patients with the polymyositis/scleroderma overlap syndrome
Authors: Raijmakers Reinout , Renz Manfred , Wiemann Claudia , Egberts Wilma Vree , Seelig Hans Peter , van Venrooij Walther J. , Pruijn Ger J. M.
Published: February 2004

Objective

To compare the autoantigenicity of the recently described N‐terminally elongated PM–Scl‐75 protein with that of PM–Scl‐100 and the originally defined PM–Scl‐75 polypeptide, and to determine its value for analyzing sera from patients with the polymyositis (PM)/scleroderma overlap syndrome.

Methods

Serum samples obtained from patients with the PM/scleroderma overlap syndrome and from patients with several other diseases were analyzed for the presence of autoantibodies reactive with recombinant PM–Scl‐100 and PM–Scl‐75 (both the original and the longer form) proteins, in an enzyme‐linked immunosorbent assay (ELISA).

Results

Autoantibodies recognizing the longer PM–Scl‐75 protein isoform were detected in 28% of the patients with PM/scleroderma. This percentage is slightly higher than that for PM–Scl‐100 (25%) and is significantly higher than that for the previously defined PM–Scl‐75 protein (11%). In addition, we identified a significant number of patients who had anti–PM–Scl‐75 but not anti–PM–Scl‐100 antibodies. This finding contrasts with what has been previously reported for the shorter version of the PM–Scl‐75 protein.

Conclusion

Our data indicate that use of the long PM–Scl‐75 isoform in addition to PM–Scl‐100 in ELISAs significantly increases the number of patients in whom anti–PM‐Scl autoantibodies can be detected.
Interleukin‐18 enhances monocyte tumor necrosis factor α and interleukin‐1β production induced by direct contact with T lymphocytes: Implications in rheumatoid arthritis
Authors: Dai Sheng‐Ming , Matsuno Hiroaki , Nakamura Hiroshi , Nishioka Kusuki , Yudoh Kazuo
Published: February 2004

Objective

At sites of inflammation, T cells exert pathologic effects through direct contact with monocyte/macrophages, inducing massive up‐regulation of interleukin‐1 (IL‐1) and tumor necrosis factor α (TNFα). We examined the regulatory effects of IL‐18 on monocyte activation by direct contact with T lymphocytes in rheumatoid arthritis (RA).

Methods

Activated T cells were isolated from RA synovial fluid. Resting T cells and monocytes were isolated from peripheral blood mononuclear cells. RA synovial T cells or phytohemagglutinin (PHA)–stimulated T cells were fixed by paraformaldehyde and then cocultured with monocytes at a ratio of 4:1. Levels of TNFα, IL‐1β, IL‐10, and IL‐18 were measured by enzyme‐linked immunosorbent assay. Expression of adhesion molecules, IL‐18 receptor, and TNF receptors was analyzed by flow cytometry. Expression of NF‐κB p65, phosphorylated IκBα, and phosphatidylinositol 3‐kinase (PI 3‐kinase) p110 was analyzed by Western blotting.

Results

IL‐18 dose‐dependently enhanced the production of IL‐1β and TNFα, but not IL‐10, by monocytes following contact with RA synovial T cells or PHA‐prestimulated T cells. NF‐κB inhibitors N‐acetyl‐L‐cysteine and Bay 11‐7085 and PI 3‐kinase inhibitor LY294002 inhibited the enhancing effects of IL‐18, but MAPK p38 inhibitor SB203580, ERK inhibitor PD98059, and JNK inhibitor SP600125 did not. Increased levels of NF‐κB in the nucleus, phosphorylated IκB, and PI 3‐kinase were confirmed in monocytes cocultured with PHA‐prestimulated T cells, and the levels were further increased by stimulation with IL‐18. Neutralizing antibody to IL‐18 inhibited monocyte activation induced by direct contact with PHA‐prestimulated T cells. Via cell–cell contact, PHA‐prestimulated T cells increased autocrine production of IL‐18 by monocytes, which was mediated by activation of the NF‐κB and PI 3‐kinase pathways, and up‐regulated the expression of the IL‐18 receptor in monocytes. IL‐18 up‐regulated the expression of the TNF receptors vascular cell adhesion molecule 1 (VCAM‐1) and intercellular adhesion molecule 1 (ICAM‐1) on monocytes. Blocking the binding of the TNF receptors VCAM‐1 or ICAM‐1 on monocytes to their ligands on stimulated T cells suppressed the IL‐18–enhanced production of TNFα and IL‐1β in monocytes induced by contact with PHA‐prestimulated T cells.

Conclusion

IL‐18 augments monocyte activation induced by contact with activated T cells in RA synovitis, which is dependent on activation of the NF‐κB and PI 3‐kinase pathways. IL‐18 up‐regulates the expression of the TNF receptors VCAM‐1 and ICAM‐1 on monocytes, which mediate the enhancing effects of IL‐18 on T cell–monocyte contact.
Religious and nonreligious coping methods among persons with rheumatoid arthritis
Authors: VandeCreek Larry , Paget Stephen , Horton Roberta , Robbins Laura , Oettinger Margaret , Tai Katie
Published: February 2004

Objective

To examine religious and nonreligious coping methods among persons with rheumatoid arthritis (RA). To identify positive and negative religious coping methods and personal characteristics associated with them.

Methods

Persons with RA (n = 181) completed a religious coping questionnaire, 6 subscales from a nonreligious coping inventory, and a depression scale.

Results

Religious and nonreligious coping were moderately correlated. The scores of all positive religious coping subscales were positively related to the importance persons attributed to religion. Scores of all negative religious coping subscales were positively associated with self‐reported depressive symptoms.

Conclusions

Correlations of religious and nonreligious coping methods were neither completely independent of each other nor functionally redundant, suggesting that each made unique contributions to coping with RA. Persons with no (or few) depressive symptoms who reported that religion was important to them tended to make positive use of their religion as they coped with the emotional stress of RA. A significant number of self‐reported depressive symptoms were correlated with a negative use of religion.
Prevalences of polyarteritis nodosa, microscopic polyangiitis, Wegener's granulomatosis, and Churg‐Strauss syndrome in a French urban multiethnic population in 2000: A capture–recapture estimate
Authors: Mahr Alfred , Guillevin Loïc , Poissonnet Marc , Aymé Ségolène
Published: February 2004

Objective

To estimate the prevalences of polyarteritis nodosa (PAN), microscopic polyangiitis (MPA), Wegener's granulomatosis (WG), and Churg‐Strauss syndrome (CSS).

Methods

Cases were collected in Seine–St. Denis County, a northeastern suburb of Paris, which has 1,093,515 adults (≥15 years), 28% of whom are of non‐European ancestry. The study period encompassed the entire calendar year 2000. Cases were identified by general practitioners, the departments of all the public hospitals and 2 large private clinics, and the National Health Insurance System. The Chapel Hill nomenclature was used to define MPA, and American College of Rheumatology criteria to define WG and CSS; PAN was diagnosed based on clinical laboratory, histological and/or angiographic findings. Three‐source capture–recapture analysis was performed to correct for incomplete case ascertainment.

Results

A total of 75 cases were retained and capture–recapture analysis estimated that 23.8 cases had been missed by any 1 of the 3 sources. Accordingly, prevalences per 1,000,000 adults (95% confidence interval [95% CI]) were estimated to be 30.7 (95% CI 21–40) for PAN, 25.1 (95% CI 16–34) for MPA, 23.7 (95% CI 16–31) for WG, and 10.7 (95% CI 5–17) for CSS. The overall prevalence was 2.0 times higher for subjects of European ancestry than for non‐Europeans (P= 0.01).

Conclusions

This study provides the first prevalence estimates for these 4 vasculitides for a multiethnic, urban population. The significantly higher prevalence observed for Europeans may infer a genetic susceptibility of Caucasians. Compared with previous estimates based mostly on rural populations, the higher frequency of PAN and the lower frequency of WG might suggest specific environmental etiologic factors.
Predicting mortality in systemic Wegener's granulomatosis: A survival analysis based on 93 patients
Authors: Bligny Dominique , Mahr Alfred , Toumelin Philippe Le , Mouthon Luc , Guillevin Loïc
Published: February 2004

Objective

To determine predictors of survival of patients with systemic Wegener's granulomatosis (WG).

Methods

We retrospectively studied 93 patients (median age 52 years, male/female ratio 1.7) with systemic WG. All subjects received cytotoxic drugs. Survival was evaluated as a function of the main clinical and laboratory parameters and 2 disease activity scores assessed at diagnosis. Statistical analyses used the multivariate Cox proportional hazards regression model.

Results

The mean followup was 4.5 years; 25 (27%) patients died. According to univariate analysis, a pejorative prognostic value was attributed to serum creatinine >160 μmole/liter (P< 0.001); age >52 years (P< 0.002); absence of ear, nose, and throat (ENT) involvement (P< 0.001); and hemoglobin ≤11.8 gm/dl (P= 0.02). Multivariate analysis retained age >52 years (hazard ratio [HR] = 3.40,P= 0.04) as an independent predictor of poor outcome, whereas the presence of ENT involvement was associated with a longer survival (HR = 0.31,P= 0.02).

Conclusion

Our results suggest that an older age and the absence of ENT involvement at diagnosis independently predict an increased risk of mortality for WG patients. These findings could indicate that the prognosis of WG might be governed by the balance between the granulomatosis as opposed to the vasculitic disease process.
Psychopathy scores and violence among juvenile offenders: a multi‐measure study
Authors: Murrie Daniel C. , Cornell Dewey G. , Kaplan Sebastian , McConville David , Levy‐Elkon Andrea
Published: February 2004

This study examined the relations between psychopathy scores and violent behavior in 113 incarcerated adolescents. We compared the results of four different instruments designed to assess psychopathy features among juveniles—the Psychopathy Checklist: Youth Version (PCL:YV), two versions of the Antisocial Processes Screening Device (APSD), and a Psychopathy Content scale on the Millon Adolescent Clinical Inventory (MACI). We found that PCLY:YV scores were significantly correlated with violent offense history, unadjudicated violence, and institutional violence, as well as measures of the severity and instrumentality of prior violence. Receiver operating characteristic analyses generated statistically significant effect sizes (AUC values) ranging from 0.64 to 0.79. The three other measures generated statistically significant correlations with one or more of the violence criteria, although correlations and effect sizes tended to be smaller in magnitude. Our results offer some support for the validity of these measures of psychopathic features, and the value of the PCL:YV in particular, with respect to short‐term measures of violence outcome among juvenile offenders. Copyright © 2004 John Wiley & Sons, Ltd.
Predictive validity of the Psychopathy Checklist: Youth Version for general and violent recidivism
Authors: Corrado Raymond R. , Vincent Gina M. , Hart Stephen D. , Cohen Irwin M.
Published: February 2004

Several authors have expressed concern regarding the use of youth psychopathy assessments in determinations of risk for general and violent offending. ThePsychopathy Checklist: Youth Version(PCL:YV) was completed with 182 male adolescent offenders in this prospective study (average 14.5 month follow‐up) of general and violent recidivism. Both a two‐factor and three‐factor model of the PCL:YV significantly predicted general and violent recidivism at a predictive accuracy ranging from 68 to 63%. However, regression analyses indicated these associations were explained primarily by behavioral psychopathic symptoms, rather than interpersonal or affective traits. Implications for the use of psychopathy assessments for risk during adolescence are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
The New Orleans Forensic Aftercare Clinic: a seven year review of hospital discharged and jail diverted clients
Authors: Bertman‐Pate Lisa Jo , Burnett Darla M.R. , Thompson John W. , Calhoun Clay J. , Deland Sarah , Fryou R. Mark
Published: February 2004

This paper provides a review of the Forensic Aftercare Clinic Conditional Release Program (FAC), which has been operating since December, 1995, in New Orleans, LA. The FAC is a community based program that provides clinical, rehabilitative, and supervisory services to individuals who have been found not guilty by reason of insanity or unrestorably incompetent to proceed and who have been discharged from inpatient settings or diverted from jail settings and placed on conditional release by district court orders. 119 clients participated in FAC over a 7 year period. Forty‐one (34.4%) had their conditional release revoked. Of the total population, 12 (10.1%) were re‐arrested on at least one charge, 3 (2.4%) were arrested on felony charges, and 9 (7.6%) on misdemeanors. Only two of these charges were violent, resulting in no significant harm to victims. Twenty (16.8%) were hospitalized at least once due to relapse. Clients diverted from jail to community settings did not differ significantly on most variables from clients who were discharged from long‐term hospitalization. Data related to public safety and client diversion demonstrate that clients, when appropriate, can be safely diverted to the community in lieu of hospitalization. The number of statewide clients who have been discharged from the forensic hospital into the community has increased steadily from 13 in 1995 to 29 in 2002, and statewide diversion clients have steadily increased from 0 in 1992 to 20 in 2002. The increase in statewide diversion clients and forensic discharges over this 7 year period indicates that stakeholders see the viability of the program as an alternative to as well as a step‐down from long‐term forensic hospitalization. Copyright © 2004 John Wiley & Sons, Ltd.
The relationship between psychopathic features, violence and treatment outcome: the comparison of three youth measures of psychopathic features
Authors: Spain Sarah E. , Douglas Kevin S. , Poythress Norman G. , Epstein Monica
Published: February 2004

Few studies have compared self‐report and clinician‐administered measures of youth psychopathic features in juvenile‐justice settings in terms of antisocial behavior and treatment indices. In a sample of 85 adjudicated delinquents, the predictive validities of the Antisocial Process Screening Device (APSD), the modified Childhood Psychopathy Scale (mCPS), and the Hare Psychopathy Checklist: Youth Version (PCL:YV) were tested. Three indices of institutional antisocial behavior (physical aggression; verbal aggression; administrative infractions) and two indices of treatment progress (time to treatment level promotion; whether treatment levels were dropped) were used as external correlates. The self‐report measures (mCPS more so than APSD) were more consistently and strongly related to antisocial behavior and to the days required to progress in treatment than the PCL:YV. The following issues are discussed: (i) implications of the potential impact of measurement format on the understanding and predictive validity of youth psychopathy features and measures; (ii) the differential predictive validity of self‐report versus clinician‐administered measures; and (iii) the potential practical utility of measures of psychopathic features in youth. Copyright © 2004 John Wiley & Sons, Ltd.
Psychopathic‐like traits in childhood: conceptual and measurement concerns
Authors: Johnstone Lorraine , Cooke David J.
Published: February 2004

Can psychopathy be identified in pre‐adolescent children? This question has both theoretical and practical implications. So far, attempts to answer this question have been made by making downward extensions of symptoms of the disorder as found in adults. We argue that for the construct of psychopathy to be viable as a construct in childhood it is necessary to demonstrate that a coherent syndrome of symptoms can be identified during childhood. To achieve this it is necessary first to use a strong measurement model, and second to use developmentally informed conceptualizations of key constructs. In order to progress from the measurement perspective, it is necessary to demonstrate (i) configural invariance of symptoms across key ages, (ii) similar performance of age cognate symptoms across key ages, and (iii) stability of relative standing on the latent trait across age. Novel techniques including item response methods and structural equation modelling techniques are required. In this paper, we review the relevant literature and evaluate the strength, or otherwise, of the evidence that key traits of psychopathy can be observed in childhood. Copyright © 2004 John Wiley & Sons, Ltd.
Validity and structure of a self‐report measure of youth psychopathy
Authors: Lexcen Frances J. , Vincent Gina M. , Grisso Thomas
Published: February 2004

An interest in early identification of youth who may be at risk of psychopathy has generated measures for age‐appropriate screening and assessment. This study examines the structural, concurrent, and divergent validity of the Psychopathy Content Scale, a 20‐item self‐report instrument derived from the Millon Adolescent Clinical Inventory (MACI). Data for 481 youths who had taken the MACI, the Child Behavior Checklist Youth Self‐Report (YSR), and the Massachusetts Youth Screening Instrument, Second Version (MAYSI‐2), were analyzed. Results showed that the PCS is best described by a two‐factor model and that analyses of the two factors offer limited support for convergent and divergent validity. High scores on both factors were associated with high YSR and MAYSI‐2 scales, suggesting that the measure identified youth who were distressed on several measures of emotional, psychological, and behavioral disorder. Copyright © 2004 John Wiley & Sons, Ltd.
The role of health professionals in preventing non‐accidental head injury
Authors: Kemp Alison , Coles Lisa
Published: February 2004

The aim of this paper is to reﬂect on the role that the health professions can play in preventing a serious form of physical child abuse. Using research data from a case series study on non‐accidental head injury, or shaken baby syndrome, some aspects of child healthcare are reviewed for their potential for prevention. In child protection in the UK, more resources are put into the diagnosis and assessment of child abuse than into interventions designed for prevention. The ﬁeld of prevention is generally lacking in a theoretical underpinning or systematic means of evaluation and yet the 1996 National Commission of Inquiry into the Prevention of Child Abuse concluded that child abuse ‘can almost always be prevented provided the will to do so is there’ (National Commission of Inquiry into the Prevention of Child Abuse, 1996). This requires major changes to the way society views and protects children. The focus in this paper is on the very young, mainly babies under 6 months of age. It calls for a lowering of the threshold with which health professionals view a baby's illness for secondary prevention of non‐accidental head injury and the need to review approaches to primary prevention, both from the UK and abroad, in order to implement a systematic means to primary prevention. Copyright © 2003 John Wiley & Sons, Ltd.
Flexible on‐line Modeling and Control of pH in Waste Neutralization Reactors
Authors: Mwembeshi M.M. , Kent Ch.A. , Salhi S.
Published: February 2004

The control of pH in waste neutralization processes presents a challenging highly nonlinear and time‐varying problem in which the reactor also suffers from inaccessible state information. The ability to characterize the changing dynamics of such reactors is essential to the success of advanced control schemes for these applications. In this work, flexible on‐line modeling of a pH reactor simulating nonstationary behavior was studied. This entailed a comparison of the most popular connectionist learning algorithm, the “Widrow‐Hoff delta rule”, with a classical tool in adaptive identification and control, recursive least squares (RLS). The modeling was pursued within the framework of neural networks using the ADALINE neural network. Further, two heuristically defined first‐principles‐based transforms were investigated for providing “general globally linearizing” information to the ADALINE. The comparisons of the learning algorithms for different neural network information vectors has led to a critical understanding of the flexibility of each algorithm for on‐line learning of the diverse process gain characteristics encountered in pH reactors.
Modular Simulation of Fluidized Bed Reactors
Authors: Jafari R. , Sotudeh‐Gharebagh R. , Mostoufi N.
Published: February 2004

Simulation of chemical processes involving nonideal reactors is essential for process design, optimization, control and scale‐up. Various industrial process simulation programs are available for chemical process simulation. Most of these programs are being developed based on the sequential modular approach. They contain only standard ideal reactors but provide no module for nonideal reactors, e.g., fluidized bed reactors. In this study, a new model is developed for the simulation of fluidized bed reactors by sequential modular approach. In the proposed model the bed is divided into several serial sections and the flow of the gas is considered as plug flow through the bubbles and perfectly mixed through the emulsion phase. In order to simulate the performance of these reactors, the hydrodynamic and reaction submodels should be integrated together in the medium and facilities provided by industrial simulators to obtain a simulation model. The performance of the proposed simulation model is tested against the experimental data reported in the literature for various gas‐solid systems and a wide range of superficial gas velocities. It is shown that this model provides acceptable results in predicting the performance of the fluidized bed reactors. The results of this study can easily be used by industrial simulators to enhance their abilities to simulate the fluidized bed reactor properly.
Neurochemical characterization of extrinsic innervation of the guinea pig rectum
Authors: Olsson Catharina , Costa Marcello , Brookes Simon J.H.
Published: February 2004

The presence of markers for parasympathetic, sympathetic, and glutamatergic or peptidergic sensory innervation was investigated by using in vitro tracing with biotinamide, combined with immunohistochemistry, to characterise quantitatively extrinsic axons to myenteric ganglia of the guinea pig rectum. Of biotinamide‐filled varicose axons, 3.6 ± 1.3% were immunoreactive for tyrosine hydroxylase (TH) and 16.0 ± 4.8% for vesicular acetylcholine transporter (VAChT). TH and vesicular monoamine transporter (VMAT1) showed high coexistence (83–100%), indicating that varicosities lacking TH immunoreactivity also lacked VMAT1. VAChT was detectable in 77% of choline acetyltransferase (ChAT)‐immunoreactive varicosities. Calcitonin gene‐related peptide (CGRP) was detected in 5.3 ± 1.6% of biotinamide‐labeled varicosities, the vesicular glutamate transporter (VGluT) 1 in 2.8 ± 0.8%, and VGluT2 in 11.3 ± 4.2% of varicosities of extrinsic origin. Varicosities from the same axon showed consistent immunoreactivity. A novel type of nerve ending was identified, with branching, flattened lamellar endings, similar to the intraganglionic laminar endings (IGLEs) of the proximal gut. Rectal IGLEs were frequently immunoreactive for VGluT1 and VGluT2. Thus most varicose axons of extrinsic origin, which innervate rectal myenteric ganglia, lack detectable levels of immunoreactivity for TH, VMAT1, VAChT, ChAT, VGluT1/2, or CGRP, under conditions in which these markers are readily detectable in other axons. Although some unlabeled varicosities may belong to afferent axons that lack detectable CGRP or VGluT1/2 in the periphery, this suggests that a large proportion of axons do not release any of the major autonomic or sensory transmitters. We speculate that this may vary under particular circumstances, for example, inflammation or obstruction of the gut. J. Comp. Neurol. 470:357–371, 2004. © 2004 Wiley‐Liss, Inc.
AII amacrine cells in the mammalian retina show disabled‐1 immunoreactivity
Authors: Lee Eun‐Jin , Kim Hyun‐Ju , Lim Eun‐Jin , Kim In‐Beom , Kang Wha‐Sun , Oh Su‐Ja , Rickman Dennis W. , Chung Jin‐Woong , Chun Myung‐Hoon
Published: February 2004

Disabled 1 (Dab1) is an adapter molecule in a signaling pathway, stimulated by Reelin, which controls cell positioning in the developing brain. It has been localized to AII amacrine cells in the mouse and guinea pig retinas. This study was conducted to identify whether Dab1 is commonly localized to AII amacrine cells in the retinas of other mammals. We investigated Dab1‐labeled cells in human, rat, rabbit, and cat retinas in detail by immunocytochemistry with antisera against Dab1. Dab1 immunoreactivity was found in certain populations of amacrine cells, with lobular appendages in the outer half of the inner plexiform layer (IPL) and a bushy, smooth dendritic tree in the inner half of the IPL. Double‐labeling experiments demonstrated that all Dab1‐immunoreactive amacrine cells were immunoreactive to antisera against calretinin or parvalbumin (i.e., other markers for AII amacrine cells in the mammalian retina) and that they made contacts with the axon terminals of the rod bipolar cells in the IPL close to the ganglion cell layer. Furthermore, all Dab1‐labeled amacrine cells showed glycine transporter‐1 immunoreactivity, indicating that they are glycinergic. The peak density was relatively high in the human and rat retinas, moderate in the cat retina, and low in the rabbit retina. Together, these morphological and histochemical observations clearly indicate that Dab1 is commonly localized to AII amacrine cells and that antiserum against Dab1 is a reliable and specific marker for AII amacrine cells of diverse mammals. J. Comp. Neurol. 470:372–381, 2004. © 2004 Wiley‐Liss, Inc.