bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated Capacity Building Needs for Water Supply and Wastewater Sanitation
Authors: Downs Timothy J.
Published: April 2005

Howe has identified key institutional water management requirements for a watershed scale: (1) coordinated management of surface water and groundwater resources, (2) coordinated management of both water quantity and water quality, (3) provision of incentives for greater economic and technical efficiencies in water use, and (4) protection of public values associated with water service (e.g., reliable, safe, clean, affordable supply). To achieve this, the water institutions must develop the following characteristics (after 1):

the capacity to coordinate water plans with other agencies (e.g., urban planning, agriculture, public health, environment, industrial);

the capacity to solve water problems creatively using a variety of options and approaches (e.g., laws, pricing, taxes, tradable supply and/or pollution permits, subsidies);

the foresight to separate roles and responsibilities for water resource planning and management activities from construction activities (i.e., avoid conflicts of interest);

the multidisciplinary capacity to undertake multicriteria/multiobjective planning and evaluation of alternatives;

devolve decision‐making power to the lowest practical level—national, state/regional (provincial), local or municipal—consistent with the scale of the water issue;

capacity and willingness to use appropriate participatory methods involving different stakeholders at different stages of a project (preplanning/conceptual, planning and design, implementation, maintenance, monitoring and evaluation);

ability to reward innovation and adapt to changing conditions and priorities.
Combined Sewer Overflow Treatment
Authors: Prochaska C. A. , Zouboulis A. I.
Published: April 2005

Combined sewer overflows (denoted hereafter as CSOs) occur when flows exceed the hydraulic capacity of either the wastewater treatment plant (denoted as WWTP) or the collection system that transports the combined flow of storm water and sanitary sewage to the WWTP. The principal components of a combined sewer system include (1) the contributing drainage area (catchment) and wastewater sources, (2) the combined sewer pipe network and interceptor(s), (3) the regulator and diversion structures, and (4) the CSO outlets.

When an overflow occurs, the excess flows tend to be discharged into the neighboring receiving body of surface water. CSOs typically discharge a variable mixture of raw sewage, industrial/commercial wastewater, polluted runoff, and scoured materials that build up in the collection system during dry weather. These discharges contain a variety of pollutants that may adversely impact the receiving waterbody, including pathogenic microorganisms, viruses, cysts, and chemical and floatable materials.
Degradation of Chloro‐Organics and Hydrocarbons
Authors: Castaldi Frank J.
Published: April 2005

Chloro‐organics include chlorinated aromatic and aliphatic compounds. The chemical characteristics of chlorinated aromatic compounds cover a range of compounds that include chlorophenols, chlorobenzenes, chloroanilines, polychlorinated biphenyls, and many pesticides. Chlorinated aliphatic compounds make up a major portion of the Environmental Protection Agency (EPA) Hazardous Substances List of halogenated volatile constituents.

The potential and extent of substance degradation of each of these compound groups differs with the complexity of the compound and the nature of the aquatic environment. The principal focus of this discussion is that of microbial degradation in water and wastewater.

Chlorinated aromatic compounds are typically produced for direct commercial use and as chemical intermediates during chemical synthesis. They are used in industrial operations to produce dyes, pharmaceuticals, pesticides, synthetic rubbers, solvents, cleaners, deodorants, pigments, and related formulations.
One‐Dimensional Assemblies of Nanoparticles: Preparation, Properties, and Promise
Authors: Tang Z. , Kotov N. A.
Published: April 2005

Nanoparticle (NP) assemblies are of considerable interest for both fundamental research and applications, since they provide direct bridges between nanometer‐scale objects and the macroscale world. Unlike two‐dimensional or three‐dimensional NP assemblies, which have been extensively studied and reviewed, reports on one‐dimensional (1D) NP assemblies are rather rare, even though these assemblies are likely to play critical roles in the improvement of the efficiencies of various electronic, optoelectronic, magnetic, and other devices based on single NPs or their composites. Additionally, 1D assemblies of NPs, i.e., chains, can significantly help in the understanding of a number of biological processes and fundamental quantum mechanics of nanometer‐scale systems. The difficulties are very evident when one wants to realize anisotropic 1D assemblies from presumably isotropic, zero‐dimensional NPs. In this context, the authors present a systemic review of current research on 1D NP assemblies. Their preparation methods are classified and novel characteristics of NP chains, such as collective properties and directional transfer of photons, electrons, spins, etc., are elucidated. Current problems underlying the fundamental research and practical applications of 1D NP assemblies are also addressed.
Cover Picture: Lithography‐Free, Self‐Aligned Inkjet Printing with Sub‐Hundred‐Nanometer Resolution (Adv. Mater. 8/2005)
Authors: Sele C. W. , von Werne T. , Friend R. H. , Sirringhaus H.
Published: April 2005

The inherently low resolution of inkjet printing on unpatterned surfaces can be overcome by selective surface modification of a first printed pattern, resulting in hydrophobic repulsion of subsequently deposited aqueous polymer dispersions. This technique, reported by Sirringhaus and co‐workers on p. 997, is capable of achieving sub‐100  nm resolution without any lithographic step. The cover shows an array of polymer transistors patterned with this method on three different length scales, as well as a schematic of the process.
Nomenklatur der Lignane und Neolignane
Authors: Schomburg Dietmar
Published: April 2005

Lignane und Neolignane sind eine große Gruppe von Naturstoffen, in denen zwei C6C3‐Einheiten miteinander verknüpft vorliegen. Für Nomenklaturzwecke wird die C6C3‐Einheit als Propylbenzol behandelt, die Ringatome werden, beginnend bei der Propylgruppe, mit 1–6 nummeriert, die Atome der Propylgruppe mit 7–9, beginnend am Benzolring. Für die zweite C6C3‐Einheit werden einfach gestrichene Nummern verwendet. Wenn die beiden C6C3‐Einheiten durch eine Bindung zwischen den Positionen 8 und 8′ verbunden sind, wird die Substanz als Lignan bezeichnet. Wenn die Verknüpfung dagegen über andere Positionen erfolgt, ist die Substanz ein Neolignan; dabei kann C‐8 oder C‐8′ sehr wohl an der Verknüpfung beteiligt sein. Gibt es keine direkte C‐C‐Bindung zwischen den C6C3‐Einheiten, sondern eine O‐Brücke, wird die Substanz Oxyneolignan genannt. Das Nomenklatursystem sieht die Benennung von weiteren Ringen und von Modifizierungen gemäß Standardverfahren der organischen Nomenklatur für Naturstoffe vor. Die Benennung der höheren Homologe wird ebenfalls behandelt: Sesquineolignane bestehen aus drei, Dineolignane aus vier C6C3‐Einheiten.
Differential effects of the immunosuppressant FK‐506 on human α2(I) collagen gene expression and transforming growth factor β signaling in normal and scleroderma fibroblasts
Authors: Asano Yoshihide , Ihn Hironobu , Yamane Kenichi , Jinnin Masatoshi , Mimura Yoshihiro , Tamaki Kunihiko
Published: April 2005

Objective

To investigate the effects of FK‐506 on the expression of the human α2(I) collagen gene and transforming growth factor β (TGFβ) signaling in normal and scleroderma fibroblasts.

Methods

The expression levels of type I procollagen protein and α2(I) collagen messenger RNA (mRNA) were analyzed by immunoblotting and Northern blotting, respectively. The promoter activities of α2(I) collagen gene and 3TP‐Lux were determined by transient transfection assay. Interaction between TGFβ receptor type I and FK‐506 binding protein 12 (FKBP12) was evaluated by immunoprecipitation.

Results

FK‐506 did not affect the basal expression of type I procollagen protein or α2(I) collagen mRNA, but it significantly reduced the TGFβ1‐induced expression of type I procollagen protein and α2(I) collagen mRNA in normal fibroblasts. The effect of FK‐506 was regulated posttranscriptionally, but not transcriptionally. In scleroderma fibroblasts, FK‐506 significantly reduced the expression of type I procollagen protein and α2(I) collagen mRNA through posttranscriptional regulation, but not transcriptional regulation. FK‐506 increased the basal activity of the 3TP‐Lux promoter, but it did not affect the TGFβ1‐induced promoter activity in normal fibroblasts. In contrast, FK‐506 did not affect the basal or the TGFβ1‐induced 3TP‐Lux promoter activity in scleroderma fibroblasts. Furthermore, FKBP12, which protects TGFβ receptor type I from ligand‐independent activation by TGFβ receptor type II, constitutively dissociated from TGFβ receptor type I in scleroderma fibroblasts.

Conclusion

FK‐506 inhibits α2(I) collagen gene expression by reducing the stability of mRNA without exhibiting its activation effect on TGFβ signaling in scleroderma fibroblasts.
Pain, stiffness, and fatigue in juvenile polyarticular arthritis: Contemporaneous stressful events and mood as predictors
Authors: Schanberg Laura E. , Gil Karen M. , Anthony Kelly K. , Yow Eric , Rochon James
Published: April 2005

Objective

To analyze patterns of stress, mood, disease symptoms, and activity reduction in children with polyarticular arthritis, using a prospective daily diary method.

Methods

For a 2‐month period, 51 children with polyarticular arthritis (mean age 12.4 years, 65% female) completed daily diaries that included measures of symptoms of pain, stiffness, and fatigue, as well as stress, mood, and activity reduction. Functional status and disease activity were assessed at the initial and followup evaluations with use of the Childhood Health Assessment Questionnaire, physician global assessment, joint count, and laboratory testing.

Results

Children reported having pain, stiffness, and fatigue on >70% of days, with significant variability in symptom levels. Results revealed significant same‐day relationships between stress, mood, and disease symptoms, after controlling for covariates. Specifically, daily fluctuations in both stress and mood were predictive of increased pain, stiffness, and fatigue. Increases in daily stress, mood, and disease symptoms were also significantly related to decreased participation in social activities on a day‐to‐day basis. Only mood and stiffness were predictors of a cutback in school attendance.

Conclusion

Stress and mood are important predictors of daily disease symptoms in children with polyarticular arthritis. Moreover, daily fluctuations in stress, mood, and disease symptoms are predictive of aspects of daily function, including participation in school and social activities. Thus, health care providers should solicit daily symptom reports when making decisions regarding clinical management. Nonpharmacologic interventions such as cognitive‐behavioral therapy and stress management may be useful adjuvant therapy when treating the disease symptoms of children with polyarticular arthritis.
Interleukin‐1 blockade by anakinra improves clinical symptoms in patients with neonatal‐onset multisystem inflammatory disease
Authors: Lovell Daniel J. , Bowyer Suzanne L. , Solinger Alan M.
Published: April 2005

Neonatal‐onset multisystem inflammatory disease (NOMID) is a rare, childhood‐onset disease that is characterized by chronic, systemic inflammation. The purpose of this report is to describe the effects of interleukin‐1 (IL‐1) blockade on the clinical symptoms of 2 patients with NOMID. At the time of this report, the patients had been treated with anakinra (Kineret), a recombinant human IL‐1 receptor antagonist, for 1.5 and 2 years, respectively. Both patients demonstrated rapid improvement in clinical symptoms and laboratory markers of inflammation. The use of anakinra in these patients seemed to be effective, without any safety concerns. These observations suggest that IL‐1 plays a critical role in the pathogenesis of this inflammatory disease, and that blockade with anakinra should be further studied as a treatment for patients with NOMID and related disorders.
Factors associated with hip cartilage volume measured by magnetic resonance imaging: The Tasmanian Older Adult Cohort Study
Authors: Zhai Guangju , Cicuttini Flavia , Srikanth Velandai , Cooley Helen , Ding Changhai , Jones Graeme
Published: April 2005

Objective

To compare associations between anthropometric and lifestyle factors and femoral head cartilage volume/thickness and radiographic features of osteoarthritis (OA) and to provide evidence of construct validity for magnetic resonance imaging (MRI) assessment of femoral cartilage volume and thickness.

Methods

We studied a cross‐sectional sample of 151 randomly selected subjects (79 men, 72 women; mean age 63 years) from the Tasmanian Older Adult Cohort Study. A sagittal T1‐weighted fat‐suppression MRI scan of the right hip was performed to determine femoral head cartilage volume, cartilage thickness, and size. An anteroposterior radiograph of the pelvis with weight bearing was performed and scored for radiographic evidence of OA in the right hip. Other factors measured were height, weight, leg strength, serum vitamin D levels, and bone mineral density.

Results

Hip cartilage volume was significantly associated with female sex, body mass index, and femoral head size, whereas hip cartilage thickness was significantly associated only with the size of the femoral head. Only female sex was significantly associated with the total radiographic OA score and the joint space narrowing (JSN) score, but not the osteophyte score. Radiographic JSN of the hip, especially axial JSN (but not osteophytes), was significantly correlated with hip cartilage volume and thickness.

Conclusion

Femoral head cartilage volume and thickness have modest but significant construct validity when correlated with radiographic findings. Furthermore, the generally stronger associations with volume compared with radiographic OA suggest that MRI may be superior at identifying risk factors for hip OA.
Expression of interleukin‐22 in rheumatoid arthritis: Potential role as a proinflammatory cytokine
Authors: Ikeuchi Hidekazu , Kuroiwa Takashi , Hiramatsu Noriyuki , Kaneko Yoriaki , Hiromura Keiju , Ueki Kazue , Nojima Yoshihisa
Published: April 2005

Objective

Interleukin‐22 (IL‐22) is a novel cytokine of the IL‐10 family. Although its pathophysiologic function is largely unknown, induction of acute‐phase responses by IL‐22 has suggested proinflammatory properties. In this study, we sought to examine whether IL‐22 plays a role in the pathogenesis of rheumatoid arthritis (RA).

Methods

Expression of IL‐22 and IL‐22 receptor 1 (IL‐22R1) was examined by reverse transcription–polymerase chain reaction (RT‐PCR), Western blot, and immunohistochemical analysis. The effects of recombinant IL‐22 (rIL‐22) on cultured synovial fibroblasts derived from RA patients (RASF), with regard to the proliferation of synovial fibroblasts and production of monocyte chemoattractant protein 1 (MCP‐1), were examined by alamer blue assay and enzyme‐linked immunosorbent assay, respectively.

Results

IL‐22 messenger RNA was detected by RT‐PCR in RA synovial tissues and mononuclear cells isolated from RA synovial fluid samples. High levels of IL‐22 were expressed both in the lining and the sublining layers of RA synovial tissues. Staining for vimentin and CD68, as markers of synovial fibroblasts and macrophages, respectively, showed that the majority of IL‐22–positive cells were synovial fibroblasts and macrophages. IL‐22R1 was also expressed in both the lining and the sublining layers of RA synovial tissues. The majority of cells expressing IL‐22R1 were positive for vimentin, but not for CD68. Expression of IL‐22 and IL‐22R1 in RASF was confirmed by RT‐PCR and Western blot analysis. In vitro, rIL‐22 significantly increased proliferation of RASF and production of MCP‐1 by RASF above the value of medium controls. Moreover, MAPK activation was induced in RASF in response to IL‐22 stimulation.

Conclusion

These data suggest that IL‐22, produced by synovial fibroblasts and macrophages, promotes inflammatory responses in RA synovial tissues by inducing the proliferation and chemokine production of synovial fibroblasts.
A new haplotype of PDCD1 is associated with rheumatoid arthritis in Hong Kong Chinese
Authors: Kong Eric Kai‐Pang , Prokunina‐Olsson Ludmila , Wong Wilfred Hing‐Sang , Lau Chak‐Sing , Chan Tak‐Mao , Alarcón‐Riquelme Marta , Lau Yu‐Lung
Published: April 2005

Objective

The programmed death 1 (PD‐1) molecule is a negative regulator of T cells, and a genetic association between PD‐1 and systemic lupus erythematosus and rheumatoid arthritis (RA) in Caucasians has been reported. The aim of this study was to investigate the association of PDCD1 polymorphisms and haplotypes with RA in the Chinese population.

Methods

Three single‐nucleotide polymorphisms (SNPs), PD‐1.1 G/A, PD‐1.3 G/A, and PD‐1.5 C/T, were genotyped in 180 patients with RA and 647 healthy controls in a case–control association study. Analyses of the association of genotypes and alleles with disease, haplotype construction, and linkage disequilibrium (LD) were performed.

Results

We constructed haplotypes with the alleles of markers PD‐1.1 G/A and PD‐1.5 C/T and found that the GT haplotype was overrepresented in patients with RA (31%) compared with controls (23%) (P = 0.001, odds ratio [OR] 1.54, 95% confidence interval [95% CI] 1.18–1.99). Among GT double homozygotes the risk of RA was increased even further (OR 2.31, 95% CI 1.31–4.08, P = 0.006). We also observed that the AA genotype of SNP PD‐1.1 was associated with a decreased risk for developing RA (OR 0.38, 95% CI 0.15–0.99, P = 0.034). No association for SNP PD‐1.5 in RA was found, and SNP PD‐1.3 was nonpolymorphic in the Chinese population.

Conclusion

Our results support the involvement of PDCD1 as a susceptibility gene for RA in the Chinese population. © 2005, American College of Rheumatology
Risk factors for functional decline in older adults with arthritis
Authors: Dunlop Dorothy D. , Semanik Pamela , Song Jing , Manheim Larry M. , Shih Vivian , Chang Rowland W.
Published: April 2005

Objective

Functional limitation is a major factor in medical costs. This study was undertaken to evaluate the prevalence of functional limitation among adults with arthritis and the frequency of functional decline over 2 years, and to investigate factors amenable to public health intervention that predict functional decline.

Methods

Longitudinal data (1998–2000) from a cohort of 5,715 adults ages 65 years or older with arthritis from a national probability sample were analyzed. Function was defined based on ability to perform basic activities of daily living (ADL) tasks and instrumental ADL. Adjusted odds ratios (ORs) from a multiple logistic regression model were used to estimate the associations between functional decline and comorbid conditions, health behaviors, and economic factors.

Results

Overall, 19.7% of this cohort had functional limitation at baseline, including 12.9% with ADL limitations. Over the subsequent 2 years, function declined in 13.6% of those at risk. Functional decline was most frequent among women (15.0%) and minorities (18.0% Hispanics, 18.7% African Americans) with arthritis. Lack of regular vigorous physical activity, the most prevalent risk factor (64%), almost doubled the odds of functional decline (adjusted OR 1.9, 95% confidence interval 1.5–2.4) after controlling for all risk factors. It was found that if all subjects engaged in regular vigorous physical activity, the expected functional decline could be reduced as much as 32%. Other significant predictors included older age, cognitive impairment, depressive symptoms, diabetes, physical limitations, no alcohol use, stroke, and vision impairment.

Conclusion

Lack of regular vigorous physical activity is a potentially modifiable risk factor that could substantially reduce functional decline and associated health care costs. Prevention/intervention programs should include regular vigorous physical activity, weight maintenance, and medical intervention for health needs. © 2005, American College of Rheumatology
MRL/Mp CD4+,CD25− T cells show reduced sensitivity to suppression by CD4+,CD25+ regulatory T cells in vitro: A novel defect of T cell regulation in systemic lupus erythematosus
Authors: Monk C. R. , Spachidou M. , Rovis F. , Leung E. , Botto M. , Lechler R. I. , Garden O. A.
Published: April 2005

Objective

To investigate the hypothesis that loss of suppression mediated by peripheral CD4+,CD25+ regulatory T cells is a hallmark of systemic lupus erythematosus (SLE).

Methods

Mice of the MRL/Mp strain were studied as a polygenic model of SLE. Following immunomagnetic selection, peripheral lymphoid CD25+ and CD25− CD4+ T cells were cultured independently or together in the presence of anti‐CD3/CD28 monoclonal antibody–coated beads. Proliferation was assessed by measuring the incorporation of tritiated thymidine.

Results

While MRL/Mp CD4+,CD25+ regulatory T cells showed only subtle abnormalities of regulatory function in vitro, syngeneic CD4+,CD25− T cells showed significantly reduced sensitivity to suppression, as determined by crossover experiments in which MRL/Mp CD4+,CD25− T cells were cultured with H‐2–matched CBA/Ca CD4+,CD25+ regulatory T cells in the presence of a polyclonal stimulus.

Conclusion

Our findings highlight a novel defect of peripheral tolerance in SLE. Identification of this defect could open new opportunities for therapeutic intervention.
Relationship between anti–double‐stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus
Authors: Linnik Matthew D. , Hu Jay Z. , Heilbrunn Kenneth R. , Strand Vibeke , Hurley Frank L. , Joh Tenshang ,   LJP 394 Investigator Consortium
Published: April 2005

Objective

To examine the relationship between changes in anti–double‐stranded DNA (anti‐dsDNA) antibody levels and the risk of renal flare in patients with systemic lupus erythematosus (SLE), using data from 2 randomized, controlled trials.

Methods

Analyses were based on 487 patients with SLE and a history of lupus nephritis who had an anti‐dsDNA antibody titer ≥15 IU/ml at baseline, as measured by Farr assay. Results are presented for the combined population of patients, the placebo arms, and the drug treatment arms in which a dsDNA‐based bioconjugate (abetimus sodium; LJP 394) was used.

Results

Changes in anti‐dsDNA antibody levels were inversely correlated with changes in the C3 level (P < 0.0001 in both trials). Cox proportional hazards regression models showed that changes in anti‐dsDNA antibody levels correlated with the risk of renal flare. The models predicted that a point estimate of a 50% reduction in anti‐dsDNA antibody levels is associated with a 52% reduction (95% confidence interval [95% CI] 26–68%, nominal P = 0.0007) and a 53% reduction (95% CI 33–69%, nominal P < 0.0001) in the risk of renal flare in the 2 trials, respectively. In the 2 trials, the incidence of renal flare was lower in patients with sustained reductions in anti‐dsDNA antibodies (3.0% and 4.1%, respectively) than in patients with stable or increasing antibody levels (21.3% and 20.3%, respectively).

Conclusion

Changes in anti‐dsDNA antibody levels were directly correlated with the risk of renal flare and inversely correlated with changes in the C3 level. Reducing anti‐dsDNA antibody levels may represent a therapeutic objective in SLE patients with lupus nephritis, because it is associated with a reduced risk of renal flare.
Pregabalin for the treatment of fibromyalgia syndrome: Results of a randomized, double‐blind, placebo‐controlled trial
Authors: Crofford Leslie J. , Rowbotham Michael C. , Mease Philip J. , Russell I. Jon , Dworkin Robert H. , Corbin Ann E. , Young James P. , LaMoreaux Linda K. , Martin Susan A. , Sharma Uma ,   Pregabalin 1008‐105 Study Group
Published: April 2005

Objective

Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and lowered pain threshold. Other prominent symptoms include disordered sleep and fatigue. FMS affects an estimated 2% of the population, predominantly women. This trial was designed to evaluate the efficacy and safety of pregabalin, a novel α2‐δ ligand, for treatment of symptoms associated with FMS.

Methods

This multicenter, double‐blind, 8‐week, randomized clinical trial compared the effects of placebo with those of 150, 300, and 450 mg/day pregabalin on pain, sleep, fatigue, and health‐related quality of life in 529 patients with FMS. The primary outcome variable was the comparison of end point mean pain scores, derived from daily diary ratings of pain intensity, between each of the pregabalin treatment groups and the placebo group.

Results

Pregabalin at 450 mg/day significantly reduced the average severity of pain in the primary analysis compared with placebo (−0.93 on a 0–10 scale) (P ≤ 0.001), and significantly more patients in this group had ≥50% improvement in pain at the end point (29%, versus 13% in the placebo group; P = 0.003). Pregabalin at 300 and 450 mg/day was associated with significant improvements in sleep quality, fatigue, and global measures of change. Pregabalin at 450 mg/day improved several domains of health‐related quality of life. Dizziness and somnolence were the most frequent adverse events. Rates of discontinuation due to adverse events were similar across all 4 treatment groups.

Conclusion

Pregabalin at 450 mg/day was efficacious for the treatment of FMS, reducing symptoms of pain, disturbed sleep, and fatigue compared with placebo. Pregabalin was well tolerated and improved global measures and health‐related quality of life.
Innate immunity and arthritis: Neutrophil Rac and toll‐like receptor 4 expression define outcomes in infection‐triggered arthritis
Authors: Zhang Xiang , Glogauer Michael , Zhu Fei , Kim Tae‐Hwan , Chiu Basil , Inman Robert D.
Published: April 2005

Objective

The role of innate immunity in Chlamydia‐induced arthritis has not been defined. The purpose of this study was to examine the role of neutrophils in experimental arthritis in mice with targeted elimination of the small GTPases Rac1 and Rac2, as well as the role of Toll‐like receptors (TLRs) in this model.

Methods

Arthritis was induced by intraarticular inoculation of synoviocyte‐packaged Chlamydia trachomatis. The degree of arthritis was assessed according to joint swelling and pathology scores. The persistence of Chlamydia in joints was assessed by immunoassay. The expression of TLR‐2 and TLR‐4 in neutrophils was detected by semiquantitative reverse transcription–polymerase chain reaction.

Results

In the acute phase, wild‐type mice developed more severe arthritis than did Rac‐deficient mice, with abundant infiltration of neutrophils into the joint. In the chronic phase, the Rac‐deficient mice developed more severe arthritis and demonstrated defective clearance of the pathogen from the joint. In vitro stimulation of neutrophils with Chlamydia up‐regulated the expression of TLR‐4, but not TLR‐2, in wild‐type mice. However, neutrophils from Rac‐deficient mice did not show this up‐regulation of TLR‐4. Sustained TLR‐4 expression in neutrophils was found to be dependent on the expression of Rac. Mice genetically deficient in TLR‐4 demonstrated more severe arthritis than did the controls. Thus, Rac expression plays a profound role in infection‐triggered arthritis and demonstrates a bimodal influence on the disease process, exacerbating acute joint inflammation but controlling chronic arthritis. Rac deficiency was associated with diminished TLR‐4 expression, impaired host clearance of the pathogen, and more severe chronic arthritis.

Conclusion

In infection‐triggered arthritis, innate immunity plays a critical role. Effective host clearance of an arthritogenic pathogen depends on intact expression of Rac and appropriate expression of TLR‐4 by neutrophils.
Inhibition of integrative cartilage repair by proteoglycan 4 in synovial fluid
Authors: Englert Carsten , McGowan Kevin B. , Klein Travis J. , Giurea Alexander , Schumacher Barbara L. , Sah Robert L.
Published: April 2005

Objective

To determine the effects of the articular cartilage surface, as well as synovial fluid (SF) and its components, specifically proteoglycan 4 (PRG4) and hyaluronic acid (HA), on integrative cartilage repair in vitro.

Methods

Blocks of calf articular cartilage were harvested, some with the articular surface intact and others without. Some of the latter types of blocks were pretreated with trypsin, and then with bovine serum albumin, SF, PRG4, or HA. Immunolocalization of PRG4 on cartilage surfaces was performed after treatment. Pairs of similarly treated cartilage blocks were incubated in partial apposition for 2 weeks in medium supplemented with serum and 3H‐proline. Following culture, mechanical integration between apposed cartilage blocks was assessed by measuring adhesive strength, and protein biosynthesis and deposition were determined by incorporated 3H‐proline.

Results

Samples with articular surfaces in apposition exhibited little integrative repair compared with samples with cut surfaces in apposition. PRG4 was immunolocalized at the articular cartilage surface, but not in deeper, cut surfaces (without treatment). Cartilage samples treated with trypsin and then with SF or PRG4 exhibited an inhibition of integrative repair and positive immunostaining for PRG4 at treated surfaces compared with normal cut cartilage samples, while samples treated with HA exhibited neither inhibited integrative repair nor PRG4 at the tissue surfaces. Deposition of newly synthesized protein was relatively similar under conditions in which integration differed significantly.

Conclusion

These results support the concept that PRG4 in SF, which normally contributes to cartilage lubrication, can inhibit integrative cartilage repair. This has the desirable effect of preventing fusion of apposing surfaces of articulating cartilage, but has the undesirable effect of inhibiting integrative repair.
Prophylactic adenovirus‐mediated human kallistatin gene therapy suppresses rat arthritis by inhibiting angiogenesis and inflammation
Authors: Wang Chrong‐Reen , Chen Shih‐Yao , Wu Chao‐Liang , Liu Ming‐Fei , Jin Ying‐Tai , Chao Lee , Chao Julie
Published: April 2005

Objective

Kallistatin has been shown to be an angiogenesis inhibitor. In this study, we investigated whether adenovirus‐mediated kallistatin gene delivery has a prophylactic effect in a rat arthritis model.

Methods

Adenovirus containing the human kallistatin gene (AdHKBP) was injected intraarticularly into ankle joints before the onset of arthritis in a rat model. The effect of kallistatin gene transfer on endothelial cell proliferation in joint extracts was assayed. The response to kallistatin treatment was determined according to clinical parameters, including ankle circumference, articular index, and radiographic scores. Hematoxylin and eosin staining was performed in order to score joint tissues and count neutrophil numbers. In addition, small vessels were quantified by identification of von Willebrand factor–positive endothelial cells. The inflammatory responses were determined by measuring tumor necrosis factor α (TNFα) and interleukin‐1β (IL‐1β) levels in ankle homogenates.

Results

The expression of recombinant human kallistatin in rat ankle joints after gene transfer was identified by immunohistochemical analysis and Western blotting. Significant reductions in the ankle circumference, articular index, and radiographic score were observed in AdHKBP‐treated rats compared with control rats treated with the adenoviral plasmid carrying green fluorescent protein. Kallistatin gene transfer also significantly ameliorated the histologic scores in ankle joints and reduced vessel density and neutrophil numbers. The inhibitory effect of kallistatin on the accumulation of inflammatory cells in ankle joints was accompanied by reduced TNFα and IL‐1β levels in joint homogenates. Furthermore, an in vitro experiment showed that the proliferation of endothelial cells was markedly inhibited by the addition of AdHKBP‐treated joint extract to the culture media, supporting a role of kallistatin in inhibiting angiogenesis.

Conclusion

This study demonstrates that kallistatin gene therapy has a prophylactic effect in inhibiting arthritis in the rat ankle. Kallistatin inhibits arthritis through its antiangiogenesis and antiinflammation activities. These results implicate potential therapeutic applications for suppression of arthritis by kallistatin gene therapy.
Association of the frizzled‐related protein gene with symptomatic osteoarthritis at multiple sites
Authors: Min J. L. , Meulenbelt I. , Riyazi N. , Kloppenburg M. , Houwing‐Duistermaat J. J. , Seymour A. B. , Pols H. A. , van Duijn C. M. , Slagboom P. E.
Published: April 2005

Objective

To confirm the association of 2 variants of the Frizzled‐related protein gene (FRZB) with osteoarthritis (OA) of the hip, and to investigate whether these variants also associate with other heritable generalized OA phenotypes.

Methods

An association analysis of 2 variants (R200W and R324G) of FRZB was performed in a random sample of 1,369 subjects (ages 55–70 years) from a population‐based cohort (the Rotterdam Study) scored for radiographic characteristics of OA in the hip, hand, spine, and knee and in a patient population of Caucasian probands (ages 40–70 years) and their siblings selected for the presence of primary symptomatic OA at multiple sites.

Results

The allele frequency of the 2 variants was not significantly different between subjects with hip radiographic OA (ROA) and controls. The frequency of the G allele of the R324G variant was significantly increased in subjects with generalized ROA from the Rotterdam Study (0.10) and in subjects from the Genetics, osteoARthritis and Progression study (0.11) compared with that in controls from the Rotterdam Study (0.08). Carriers of this G allele had increased susceptibility for generalized ROA (odds ratio [OR] 1.4, 95% confidence interval [95% CI] 0.9–1.9, P = 0.10) or familial symptomatic OA at multiple sites (OR 1.6, 95% CI 1.1–2.3, P = 0.02).

Conclusion

Our results confirm that the R324G variant of the FRZB gene is involved in OA and indicate a role of this variant in several generalized OA phenotypes. A more extended OA phenotype may indeed be expected from genetic variation in an essential pathway of skeletal development such as Wnt signaling.
Bilateral subchondral insufficiency fracture of the femoral head after renal transplantation: A case report
Authors: Ikemura Satoshi , Yamamoto Takuaki , Nakashima Yasuharu , Shuto Toshihide , Jingushi Seiya , Iwamoto Yukihide
Published: April 2005

This report describes the case of a 47‐year‐old woman who was found to have subchondral insufficiency fractures in both femoral heads after renal transplantation. Initially, plain radiographs showed no obvious changes, but magnetic resonance imaging (MRI) revealed an irregular, discontinuous, low‐intensity band on the T1‐weighted image of both hips. The patient was treated nonsurgically. Ten months after onset, the pain in both hips disappeared, and plain radiographs and MRI showed no abnormalities. Subchondral insufficiency fracture should be considered in the diagnosis of patients who have hip pain after renal transplantation.
Association of Epstein‐Barr virus with systemic lupus erythematosus: Effect modification by race, age, and cytotoxic T lymphocyte–associated antigen 4 genotype
Authors: Parks Christine G. , Cooper Glinda S. , Hudson Lori L. , Dooley Mary Anne , Treadwell Edward L. , St.Clair E. W. , Gilkeson Gary S. , Pandey Janardan P.
Published: April 2005

Objective

Epstein‐Barr virus (EBV) is hypothesized to play a role in the development of systemic lupus erythematosus (SLE). Cytotoxic T lymphocyte–associated antigen 4 (CTLA‐4) is important in regulating T cell–mediated immunity, encompassing the first line of response to viral infections, and genetic variation in CTLA‐4 has been associated with SLE. This study examined the seroprevalence of EBV in a population‐based study of SLE patients from the southeastern United States, and potential interactions with CTLA‐4 polymorphisms were assessed.

Methods

Cases comprised 230 subjects recently diagnosed as having SLE (144 African American and 86 white) from university and community‐based clinics, and controls comprised 276 age‐, sex‐, and state‐matched subjects (72 African American and 204 white) recruited from driver's license registries. Antibodies to EBV capsid antigen were determined by enzyme‐linked immunosorbent assay, with results expressed as positive or negative using the international standardized ratio (ISR) (a ratio of the sample absorbance to a known standard). CTLA‐4 genotypes were identified by polymerase chain reaction–based methods.

Results

In African Americans, EBV‐IgA seroprevalence was strongly associated with SLE (odds ratio [OR] 5.6, 95% confidence interval [95% CI] 3.0–10.6). In whites, the modest association of SLE with EBV‐IgA (OR 1.6) was modified by age, in that the strongest association was observed in those older than age 50 years (OR 4.1, 95% CI 1.6–10.4). The seroprevalence of EBV‐IgM and that of EBV‐IgG were not associated with SLE. Higher EBV‐IgG absorbance ratios were observed in SLE patients, with a significant dose response across units of the ISR in African Americans (P < 0.0001). Allelic variation in the CTLA‐4 gene promoter (−1661A/G) significantly modified the association between SLE and EBV‐IgA (P = 0.03), with a stronger association among those with the −1661AA genotype.

Conclusion

These findings suggest that repeated or reactivated EBV infection, which results in increased EBV‐IgA seroprevalence and higher IgG antibody titers, may be associated with SLE, and that the CTLA‐4 genotype influences immune responsiveness to EBV in SLE patients. The observed patterns of effect modification by race, age, and CTLA‐4 genotype should be examined in other studies and may help frame new hypotheses regarding the role of EBV in SLE etiology.
Elevated expression of the Brn‐3a and Brn‐3b transcription factors in systemic lupus erythematosus correlates with antibodies to Brn‐3 and overexpression of Hsp90
Authors: Ripley B. J. M. , Rahman M. A. , Isenberg D. A. , Latchman D. S.
Published: April 2005

Objective

Important developmental and antiapoptotic roles have been described for the Brn‐3 family of transcription factors in mammalian cells. Following a report of pathogenic autoantibody‐inducing T cell reactivity to the Brn‐3 transcription factors in murine lupus, we undertook this study to investigate serum levels of antibodies to Brn‐3 and levels of expression of Brn‐3 in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE).

Methods

Serum and PBMC samples were obtained from 87 SLE patients and 30 normal control subjects. Serum antibodies to the Brn‐3a and Brn‐3b transcription factors were measured by enzyme‐linked immunosorbent assay. Levels of Brn‐3a and Brn‐3b messenger RNA (mRNA) in PBMCs were measured by reverse transcription and real‐time quantitative polymerase chain reaction.

Results

Elevated serum levels of antibodies to Brn‐3a and Brn‐3b were found in 43% and 32%, respectively, of SLE patients. This elevation paralleled enhanced expression of Brn‐3a and Brn‐3b in PBMCs of 44% and 31%, respectively, of SLE patients. Furthermore, we observed a significant correlation (P = 0.002) between elevated levels of anti–Brn‐3b antibodies and elevated levels of Brn‐3b mRNA in individual patients. A preliminary analysis of possible target genes for Brn‐3a and Brn‐3b revealed a significant correlation (P = 0.01) between the level of Brn‐3a mRNA and the level of Hsp90 protein (90‐kd heat‐shock protein, which is overexpressed in SLE) in PBMCs of SLE patients. In addition, we observed that overexpression of Brn‐3a and Brn‐3b in cultured cells enhanced expression of Hsp90 protein and transcription of Hsp90 promoter–reporter constructs. Finally, we observed an association between elevated levels of Brn‐3a mRNA and active SLE (P = 0.002).

Conclusion

Expression of both Brn‐3a and Brn‐3b was found to be enhanced in SLE, and this correlated with enhanced levels of autoantibodies to these proteins and with the previously reported overexpression of Hsp90, which was shown to be a novel gene regulated by Brn‐3a and Brn‐3b. The overexpression of Brn‐3a correlated with active disease, suggesting that it may play a role in the disease process via its targeting by the immune system and its ability to induce the expression of specific genes.
Anaerobic exercise capacity in patients with juvenile‐onset idiopathic inflammatory myopathies
Authors: Takken Tim , van der Net Janjaap , Helders Paul J. M.
Published: April 2005

Objective

To 1) report the feasibility of an “all‐out” 30‐second cycling exercise test (Wingate Anaerobic Exercise Test [WAnT]) in juvenile‐onset idiopathic inflammatory myopathy (JIIM) patients, 2) describe the anaerobic exercise capacity in juvenile dermatomyositis patients, and 3) determine if the anaerobic exercise capacity could be related to disease duration or disease phase.

Methods

Twenty patients (age 14.13 ± 5.4 years) with JIIM participated in this study. All patients were able to perform the WAnT without adverse events.

Results

Comparison with healthy controls revealed a −29.3 ± 26.58% (P = 0.001) and −27.6 ± 25.7% (P = 0.002) impairment in mean power and peak power on the WAnT, respectively. The WAnT correlated with disease phase and with knee extensor muscle strength.

Conclusion

The WAnT might be a valuable adjunct next to other assessment tools in the followup of JIIM patients.
Remitting seronegative symmetrical synovitis with pitting edema of the hands: Ultrasound, color doppler ultrasound, and magnetic resonance imaging findings
Authors: Klauser Andrea , Frauscher Ferdinand , Halpern Ethan J. , Mur Erich , Springer Peter , Judmaier Werner , Schirmer Michael
Published: April 2005

Objective

To assess the value of gray‐scale ultrasound (US), color Doppler ultrasound (CDUS), contrast‐enhanced CDUS, and magnetic resonance imaging (MRI) in the diagnostic evaluation of the hands in patients with remitting seronegative symmetrical synovitis with pitting edema (RS3PE).

Methods

Eight patients (5 men, 3 women; mean ± SD age 69.3 ± 7.2 years) with clinical diagnosis of RS3PE syndrome underwent US, CDUS, contrast‐enhanced CDUS, and MRI. US was performed with a linear array transducer operating at 12 MHz. The US contrast agent (SHU 508; Levovist, Schering, Germany) was intravenously infused in a concentration of 300 mg/ml at a rate of 1 ml/minute.

Results

All patients showed symmetric subcutaneous edema and synovitis of tendons and finger joints on both US and MRI. Vascularity was detected subcutaneously in tendon sheaths and in the joint synovia on CDUS and MRI. Detection of increased vascularity was improved after contrast administration compared with unenhanced CDUS (P < 0.01).

Conclusion

Ultrasound, CDUS, contrast‐enhanced CDUS, and MRI are valuable tools in the diagnostic evaluation of involved anatomic structures in patients with RS3PE. Contrast‐enhanced CDUS is superior to CDUS in assessment of inflammatory edema, effusion, and synovitis.
History of infection before the onset of juvenile dermatomyositis: Results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Research Registry
Authors: Pachman Lauren M. , Lipton Rebecca , Ramsey‐Goldman Rosalind , Shamiyeh Eli , Abbott Kathy , Mendez Eduardo P. , Dyer Alan , Curdy Deborah Mc , Vogler Larry , Reed Ann , Cawkwell Gail , Zemel Lawrence , Sandborg Christy , Rivas‐Chacon Rafael , Hom Christine , Ilowite Norman , Gedalia Abraham , Gitlin Jonathan , Borzy Michael
Published: April 2005

Objective

To obtain data concerning a history of infection occurring in the 3 months before recognition of the typical weakness and rash associated with juvenile dermatomyositis (JDM).

Methods

Parents or caretakers of children within 6 months of JDM diagnosis were interviewed by the registry study nurse concerning their child's symptoms, environment, family background, and illness history. Physician medical records were reviewed, confirming the JDM diagnosis.

Results

Children for which both a parent interview and physician medical records at diagnosis were available (n = 286) were included. Diagnoses were as follows: definite/probable JDM (n = 234, 82%), possible JDM (n = 43, 15%), or rash only (n = 9, 3%). The group was predominantly white (71%) and had a girl:boy ratio of 2:1. Although the mean age at onset was 6.7 years for girls and 7.3 years for boys, 25% of the children were ≤4 years old at disease onset. In the 3 months before onset, 57% of the children had respiratory complaints, 30% had gastrointestinal symptoms, and 63% of children with these symptoms of infection were given antibiotics.

Conclusion

This study provides evidence that JDM affects young children. The symptoms of the typical rash and weakness often follow a history of respiratory or gastrointestinal complaints. These data suggest that the response to an infectious process may be implicated in JDM disease pathogenesis.
Two major spondylarthropathy phenotypes are distinguished by pattern analysis in multiplex families
Authors: Porcher Raphaël , Said‐Nahal Roula , D'Agostino Maria‐Antonietta , Miceli‐Richard Corinne , Dougados Maxime , Breban Maxime
Published: April 2005

Objective

To examine whether spondylarthropathy (SpA) disease manifestations would combine in any ordered pattern among patients from SpA multiplex families.

Methods

SpA patients (n = 540) belonging to 190 multiplex families were thoroughly investigated. Clinical data was collected, systematic pelvic radiographs were taken, and HLA–B27 status was determined. The patterns of SpA manifestations were examined by several methods, including multiple correspondence analysis, nonhierarchical and hierarchical clustering, and discriminant analysis.

Results

The nonhierarchical cluster analysis allowed us to classify patients, independent of disease duration, into 2 major groups of comparable size. Group A contained a majority of the women, whereas group B predominantly consisted of men. The 2 groups were very similar regarding axial symptoms, radiographic sacroiliitis, and uveitis. Group B was characterized by a younger age at onset and a higher frequency of clinical enthesitis, peripheral arthritis, dactylitis, psoriasis, and inflammatory bowel disease than group A. Patients belonging to those groups exhibited some degree of familial aggregation, thereby supporting their intrinsic validity.

Conclusion

Pattern analysis of SpA manifestations among familial SpA allowed us to recognize 2 main clusters independent of disease duration. Furthermore, there was a trend toward aggregation by cluster among families, suggesting that they are determined by specific genetic factors. These clusters may indeed correspond to different severity patterns.