bluuebunny/crossref_metadata_2025 huggingface dataset:
Meeting the Challenge: Using Policy to Improve Children’s Health
Authors: Brush Charles Adam , Kelly Maggie M. , Green Denise , Gaffney Marcus , Kattwinkel John , French Molly
Published: September 2005

We reflect on the proceedings of a symposium at a conference of the Centers for Disease Control and Prevention National Center on Birth Defects and Developmental Disabilities. We present examples of bridging the gap between science and policy to achieve improvements in children’s health through case studies in early hearing detection and intervention, folic acid fortification to prevent birth defects, sleep positioning recommendations to reduce infant mortality, and workplace lactation support programs.

We discuss case studies that present different policy strategies (public health law and voluntary practices) for improving public health. These case studies demonstrate both the power of policy as a tool for improving children’s health and the challenges of communicating public health research to policy decisionmakers.
Decreased Attendance at Cystic Fibrosis Centers by Children Covered by Managed Care Insurance
Authors: Nathanson Ian , Ramírez-Garnica Gabriela , Wiltrout Stacey Armatti
Published: September 2005

Objective. The evolution of managed care has raised concerns about differential access to care for children with cystic fibrosis (CF). We tested the hypothesis that children with CF with managed care attended CF centers less frequently compared with children with non-managed care.

Methods. We conducted a prospective cohort study by telephone every 4 months to measure access to care at CF centers among 630 randomly selected patients aged 6–18 years from 15 US CF centers. We analyzed data with unconditional logistic regression and generalized estimating equations.

Results. Attendance at CF centers was significantly reduced among children with managed care (odds ratio [OR] = 0.74; 95% confidence interval [CI] = 0.57, 0.98; P=0.03) and among girls (OR=0.68; 95% CI=0.48, 0.97; P=0.04).

Conclusions. Children with CF with managed care attended CF centers significantly less frequently than those with non-managed care. These findings suggest that children with CF with managed care may not have equal access to experts in CF as children with non-managed care. Families should consider this when selecting their medical insurance plan. These findings may apply to other children with special health care needs.
Health-Related Quality of Life, Health Risk Behaviors, and Disability Among Adults With Pain-Related Activity Difficulty
Authors: Strine Tara W. , Hootman Jennifer M. , Chapman Daniel P. , Okoro Catherine A. , Balluz Lina
Published: September 2005

Objectives. We examined the association between pain-related activity difficulty (PRAD) in the past 30 days and health-related quality of life, health behaviors, disability indices, and major health impairments in the general US population.

Methods. We obtained data from 18 states in the 2002 Behavioral Risk Factor Surveillance System, an ongoing, cross-sectional, state-based, random-digit-dialed telephone survey of noninstitutionalized adults aged 18 years or older.

Results. Nearly one quarter of people in the 18 states and the District of Columbia reported at least 1 day of PRAD in the past 30 days. PRAD was associated with obesity, smoking, physical inactivity, impaired general health, infrequent vitality, and frequent occurrences of physical distress, mental distress, depressive symptoms, sleep insufficiency, and anxiety symptoms. Moreover, a general dose–response relationship was noted between increased days of PRAD and increased prevalence of impaired health-related quality of life, disability indices, and health risk behaviors.

Conclusion. Pain negatively influences various domains of health, not only among clinical populations, but also in the general community, suggesting a critical need for the dissemination of targeted interventions to enhance recognition and treatment of pain among adult community-dwellers.
Ground‐Based Forest Harvesting Effects on Soil Physical Properties and Douglas‐Fir Growth
Authors: Ares Adrian , Terry Thomas A. , Miller Richard E. , Anderson Harry W. , Flaming Barry L.
Published: September 2005

Soil properties and forest productivity can be affected by heavy equipment used for harvest and site preparation but these impacts vary greatly with site conditions and operational practices. We assessed the effects of ground‐based logging on soil physical properties and subsequent Douglas‐fir [Pseudotsuga menziesii (Mirb) Franco] growth on a highly productive site receiving vegetation control in coastal Washington. We also tested the effectiveness of tillage in maintaining or enhancing site productivity. On average, about half of the area of ground‐based harvested plots was affected by vehicular traffic. Sixty‐three percent of the trees were planted on microsites with some degree of soil disturbance. Soil bulk density at the 0‐ to 30‐cm depth increased from 0.63 to 0.82 Mg m−3 in the most compacted portions of traffic lanes. The area‐weighted increase in soil bulk density in the 0‐ to 30‐cm depth was 27%. Soil strength in traffic lanes increased at all depths < 55 cm but never exceeded 1300 kPa. Tillage to the 60‐cm depth returned the soil to its initial strength condition. Volumetric soil water content in compacted traffic lanes was greater than that in noncompacted soil. Total soil porosity decreased 10 to 13% with compaction, while available water holding capacity increased. In compacted soil, macropore space was reduced 40 to 52%. The study revealed no detrimental effects on tree height and diameter from soil compaction at age 4. At stand age 3, a tree volume index was actually greater for trees planted on traffic lanes than for those on non‐disturbed soil.
Soil Physical Disturbance and Logging Residue Effects on Changes in Soil Productivity in Five‐Year‐Old Pine Plantations
Authors: Eisenbies Mark H. , Burger James A. , Aust W. Michael , Patterson Steve C.
Published: September 2005

There has been much concern that traffic associated with the harvesting of intensively managed pine plantations reduces long‐term soil‐site productivity. Trafficking, especially during wet periods, can cause severe soil physical disturbance and redistribution of woody residues. Although the negative effects of soil compaction and rutting on root growth and the importance of organic matter for maintaining site productivity are well known, the connection between these factors and actual changes in soil and site productivity has been difficult to evaluate. Three productive, 20‐ha loblolly pine (Pinus taeda L.) plantations located on fertile “wet pine flats” on the coastal plain of South Carolina were subjected to wet‐ and dry‐weather harvesting and mechanical site preparation. A factorial design was used to evaluate changes in soil‐site quality after 5 yr based on postharvest classifications of soil physical disturbance, harvest residue removal, and the type of site preparation using a recently developed rank diagnostic approach. Trees on disturbed sites performed as well or better than trees on minimally disturbed sites with average levels of harvest residues. Bedding restored relative soil‐site productivity (based on the rank diagnostic) on all but heavily disturbed sites with >25% bare soil; however, these heavily disturbed sites comprised about 5% of the total area harvested. Moderate levels of disturbance may increase relative soil‐site productivity, perhaps by controlling competition or increasing nitrogen mineralization rates. Sites such as these may be good alternatives to more sensitive sites for wet‐weather harvesting.
The Shrinkage Geometry Factor of a Soil Layer
Authors: Chertkov V. Y.
Published: September 2005

The shrinkage geometry factor connects the changes of subsidence and the total crack volume at the shrinkage of a soil layer matrix. An available approach for estimating the factor does not account for the crack volume in samples, the stretching of a shrinking soil layer, and a possible change of the factor with water content. A recent new approach for estimation of the factor enables one to account for the factor's dependence on water content and the impact of cracks in a sample. The present work also accounts for the stretching of a shrinking soil layer. Corrected value of the factor is described in terms of the shrinkage curves of: a layer including unconnected solid cubes from the available approach, a stretched layer with cracks, a sample with cracks, and the soil matrix without cracks. This correction leads to changes in the soil subsidence and total crack volume compared with those obtained from the available approach. Two known physical conditions are used: the specific soil matrix volume without cracks is the same for the sample and the layer; and, the matrix deformations of an unlimited shrinking soil layer are longitudinal those of a thin quasi‐elastic plate. Two available experimental examples are considered. The former relates to clay paste samples. The latter relates to an aggregated clay soil in situ and in samples. The geometry factor from the available approach, and that obtained after correction, differ significantly. The corrected factor also shows the appreciable change with water content.
Sorption‐Desorption Behavior of Atrazine in Soils Irrigated with Reclaimed Wastewater
Authors: Drori Yaron , Aizenshtat Zeev , Chefetz Benny
Published: September 2005

A time‐dependent sorption–desorption study of atrazine (2‐chloro‐4‐ethylamino‐6‐isopropylamine‐s‐triazine) was performed to reveal its behavior in wastewater‐ and freshwater‐irrigated soils. Atrazine sorption affinity to the freshwater‐irrigated soils was significantly higher than to their wastewater‐irrigated counterparts. The calculated C‐normalized partition coefficient (KOC) values for the freshwater‐irrigated soils were 70.7 and 34.2 L kg−1 organic C and the values for the wastewater‐irrigated soils were 52.6 and 29.9, respectively, for the two tested soils. These differences did not result from atrazine interactions with dissolved organic matter (DOM) in the wastewater‐irrigated soils. All desorption isotherms exhibited hysteresis. Lower desorption was exhibited for the 14‐d sorption–desorption experiments, even though the sorption‐affinity parameters were similar for the 2‐ and 14‐d sorption periods. Higher desorption hysteresis was observed for the longer sorbate‐sorbent contact time for both soils, with desorption decreasing for decreased atrazine loading. The similar atrazine‐sorption parameters obtained for the two sorption periods and the increasingly difficult desorption with increasing contact time suggest that the sorption process occurs in two stages. First, sorption occurs to readily available sites; at a later stage, the sorbed molecules interact with the soil organic matter (SOM) or the SOM‐mineral complexes such that their desorption ability is significantly hindered. The higher sorption potential and the lower desorption ability of the freshwater‐irrigated soils suggest that the SOM which develops in the wastewater‐irrigated soils delays or hinders atrazine interaction with sites that are naturally present in these soils.
Soil Moisture and Temperature Effects on Nitrogen Release from Organic Nitrogen Sources
Authors: Agehara S. , Warncke D. D.
Published: September 2005

Nitrogen release from organic N sources is controlled by the soil environment. Soil incubation was conducted to evaluate the effects of soil moisture (50, 70, and 90% of water holding capacity) and temperature (15/10, 20/15, and 25/20°C [14/10 h]) on N release from four organic N sources. Differential N release kinetics of the N sources were determined by measuring ammonium‐ and nitrate‐N contents periodically over 12 wk. Net N released, as a percentage of organic N, was greatest in the order: urea (91–96%) > blood meal (BM) (56–61%) > alfalfa pellets (AP) (41–52%) > partially composted chicken manure (CM) (37–45%). Increasing soil moisture increased net N released from AP and CM by 12 and 21%, respectively, but did not significantly affect net N released from urea and BM. Increasing temperature increased net N released from AP, BM, and CM by 25, 10, and 13%, respectively, but did not significantly affect net N released from urea. The results indicate that soil moisture and temperature influence N availability from organic N materials differently depending on source of N. In greenhouse production systems, where irrigation and temperature can be controlled, fertilizer management that considers both source of N and soil environment may improve the effectiveness of organic N materials.
Rhizosphere Iron (III) Deposition and Reduction in a Juncus effusus L.‐Dominated Wetland
Authors: Weiss Johanna V. , Emerson David , Megonigal J. Patrick
Published: September 2005

Iron (III) plaque forms on the roots of wetland plants from the reaction of Fe(II) with O2 released by roots. Recent laboratory studies have shown that Fe plaque is more rapidly reduced than non‐rhizosphere Fe(III) oxides. The goals of the current study were to determine in situ rates of: (i) Fe(III) reduction of root plaque and soil Fe(III) oxides, (ii) root Fe(III) deposition, and (iii) root and soil organic matter decomposition. Iron (III) reduction was investigated using a novel buried‐bag technique in which roots and soil were buried in heat‐sealed membrane bags (Versapor 200 membrane, pore size = 0.2 μm) in late fall following plant senescence. Bags were retrieved at monthly intervals for 1 yr to assess changes in total C and Fe mass, Fe mineralogy, Fe(II)/Fe(III) ratio, and the abundances of Fe(II)‐oxidizing bacteria (FeOB) and Fe(III)‐reducing bacteria (FeRB). The soil C and Fe pools did not change significantly throughout the year, but root C and total root Fe mass decreased by 40 and 70%, respectively. When total Fe losses were adjusted for changes in the ratio of Fe(II)/Fe(III), over 95% of the Fe(III) in the plaque was reduced during the 12‐mo study, at a peak rate of 0.6 mg Fe(III) g dry weight−1 d−1 (gdw−1 d−1). These estimates exceed the crude estimate of Fe(III) accumulation [0.3 mg Fe(III) g dry weight−1 d−1] on bare‐root plants that were transplanted into the wetland for a growing season. We concluded that root plaque has the potential to be reduced as rapidly as it is deposited under field conditions.
Soil Organic Carbon Composition in a Northern Mixed‐Grass Prairie
Authors: Ganjegunte Girisha K. , Vance George F. , Preston Caroline M. , Schuman Gerald E. , Ingram Lachlan J. , Stahl Peter D. , Welker Jeffrey M.
Published: September 2005

Growing interest in the potential for soils to provide a sink for atmospheric C has prompted studies of effects of management on the amount and nature of soil organic C (SOC). In this study, we evaluated effects of different grazing management regimes (light grazing [LG], heavy grazing [HG], and non‐grazed exclosures [EX]) on amount and composition of SOC at the USDA–ARS High Plains Grasslands Research Station (HPGRS), Cheyenne, WY. Soils (0–5 cm) from each treatment were analyzed for total C and N contents and lignin composition. Soil organic C and N contents were significantly greater in LG (SOC–13.8 Mg ha−1; total N–1.22 Mg ha−1) than HG (SOC–10.9 Mg ha−1; total N–0.94 Mg ha−1) or EX (SOC–10.8 Mg ha−1; total N–0.94 Mg ha−1). From CuO oxidation studies, significantly greater (P < 0.05) total lignin (Vanillyl [V] + Syringyl [S] + Cinnamyl [C] compounds) contents were noted in EX (21 g kg−1 SOC) than LG (12 g kg−1 SOC) and HG (15 g kg−1 SOC) soils. The lignin composition of humic (HA) and fulvic (FA) acids indicated that HA under LG contained significantly greater V and S than HG or EX. Fulvic acids contained S‐depleted lignin compared with HAs and FAs from HG, which contained significantly greater V and C than FAs extracted from LG and EX. Nuclear magnetic resonance (NMR) spectra of HA and FA, however, did not vary significantly among the three grazing treatments. Results from CuO oxidation and NMR spectroscopy emphasized the familiar problem that determining the nature of soil organic matter (SOM) is a difficult task and sometimes different analytical techniques provide different information about the nature of SOM. Nonetheless, results of this study indicate that LG is the most sustainable grazing management system for northern mixed‐grass prairies.
Control of a multiunit heterogeneous azeotropic distillation process
Authors: Luyben William L.
Published: September 2005

An investigation of the design and control of a system in which a heterogeneous azeotrope permits the use of a decanter to cross a distillation boundary is reported. The specific numerical example is the classical production of anhydrous ethanol from an ethanol/water mixture using benzene as the entrainer. The feed is an ethanol/water mixture with composition that is near the binary azeotrope, which has been produced in an upstream binary distillation column. The process consists of two columns in which the addition of benzene takes the water out the top of the first column, producing high‐purity ethanol out the bottom. The overhead vapor is condensed and forms two liquid phases. The organic benzene‐rich phase provides reflux to the first column. The aqueous phase is fed to a second distillation column that produces high‐purity water out the bottom and recycles the distillate back to the first column. The steady‐state convergence of this two‐column system with two‐recycles if very difficult. Convergence is achieved by using a dynamic model. A plantwide control scheme is developed and is shown to provide stable base‐level regulatory control for very large disturbances. The control structure has a counter‐intuitive feature. The aqueous level in the decanter is controlled by manipulating the flow rate of the aqueous stream from the decanter. The action of the level controller is the reverse of what is used conventionally, that is, if the level is increasing, the exit flow rate is decreased! © 2005 American Institute of Chemical Engineers AIChE J, 2006
Centrifugal drum filtration: II. A compression rheology model of cake draining
Authors: Barr John D. , White Lee R.
Published: September 2005

A compression rheology model for the final capillary compression and draining stages of the batch centrifugal filtration of a compressible cake is presented. The initial stage of cake formation and drainage of the supernatant fluid have been treated in a companion paper up to the point tc, where the supernatant first contacts the top of the cake. The compressional rheology model uses the compressive yield stress py(ϕ), the hydrodynamic resistance R(ϕ), and the maximum capillary stress P(ϕ). Analysis of these final stages indicates that the system can remain fully saturated if the solids network can sustain the capillary stress and, if not, will partially unsaturate. The controlling parameters are elucidated and the state of the system for tc < t < ∞ is illustrated graphically for the previously treated model system. © 2005 American Institute of Chemical Engineers AIChE J, 2006
Similar cell surface expression of β2‐microglobulin–free heavy chains by HLA–B27 subtypes differentially associated with ankylosing spondylitis
Authors: Vázquez Miriam N. , López de Castro José A.
Published: September 2005

Objective

To determine whether the cell surface features of HLA–B27 subtypes reported to be differentially associated with ankylosing spondylitis (AS) differ in a way that correlates with disease susceptibility.

Methods

Human cell transfectants expressing or lacking the transporter associated with antigen processing were used to determine the cell surface expression of B27 subtypes by flow cytometry with antibodies recognizing the B27 heterodimer or β2‐microglobulin (β2m)–free heavy chains.

Results

In lymphoid cells with an intact peptide‐loading complex, all B27 subtypes, irrespective of their association with disease, showed similar ratios of free heavy chain to heterodimer, suggesting similar surface stability. A substantial decrease in dissociated heavy chains, which never reached 100%, was observed upon addition of a B27 ligand, with no significant differences among subtypes. This is compatible with similar surface expression of irreversible β2m‐free heavy chain forms among subtypes differentially associated with disease. In cells lacking the transporter associated with antigen processing, both disease‐associated and non–disease‐associated subtypes expressed a population of heterodimers at 26°C that was less stable than the population expressed at 37°C. In the presence of exogenous peptide, the expression of heterodimers increased, without a concomitant decrease in β2m‐free heavy chains. This suggests that in these cells, and for all subtypes tested, most of the dissociated heavy chains at the cell surface are in irreversible forms. At 37°C, the expression of β2m‐free B27 heavy chains was very low on T2 transfectant cells.

Conclusion

HLA–B27 subtypes showing differential associations with AS are similar in their extent of β2m dissociation and surface expression of free heavy chains.
Increased coronary‐artery atherosclerosis in rheumatoid arthritis: Relationship to disease duration and cardiovascular risk factors
Authors: Chung Cecilia P. , Oeser Annette , Raggi Paolo , Gebretsadik Tebeb , Shintani Ayumi K. , Sokka Tuulikki , Pincus Theodore , Avalos Ingrid , Stein C. Michael
Published: September 2005

Objective

To compare the prevalence and severity of coronary‐artery atherosclerosis in patients with early and established rheumatoid arthritis (RA) and controls.

Methods

Electron‐beam computed tomography was used to measure the extent of coronary‐artery calcification in 227 subjects, of whom 70 had early RA, 71 had established RA, and 86 were controls. Coronary‐artery calcification calculated according to the Agatston calcium score was compared in patients and controls, and its relationship to clinical characteristics was examined. Adjusted odds ratios (ORs) were obtained with the use of proportional odds logistic regression models to determine independent associations of early and established RA and coronary‐artery calcification.

Results

Calcium scores were higher in patients with established RA (median 40.2, interquartile range [IQR] 0–358.8) compared with those with early disease (median 0, IQR 0–42.6) and controls (median 0, IQR 0–19.2) (P = 0.001). Coronary‐artery calcification occurred more frequently in patients with established RA (60.6%) than in patients with early RA (42.9%) and control subjects (38.4%) (P = 0.016) The OR for the likelihood of having more severe coronary‐artery calcification (defined as an Agatston score >109) in patients with established disease was 3.42 (P = 0.002) after adjusting for cardiovascular risk factors. Among patients with RA, smoking (OR 1.02, P = 0.04) and an elevated erythrocyte sedimentation rate (OR 1.02, P = 0.05) were associated with more severe coronary‐artery calcification after adjustment for age and sex.

Conclusion

The prevalence and severity of coronary calcification is increased in patients with established RA and is related, in part, to smoking and an increased erythrocyte sedimentation rate.
Involvement of transient receptor potential vanilloid 1 in the vascular and hyperalgesic components of joint inflammation
Authors: Keeble Julie , Russell Fiona , Curtis Bradley , Starr Anna , Pinter Erika , Brain Susan D.
Published: September 2005

Objective

To investigate the endogenous involvement of transient receptor potential vanilloid 1 (TRPV1) in a model of knee joint inflammation in the mouse.

Methods

Following characterization of wild‐type (WT) and TRPV1‐knockout mice, inflammation was induced via intraarticular (IA) injection of Freund's complete adjuvant (CFA). Knee swelling was assessed as diameter, and inflammatory heat hyperalgesia was determined using the Hargreaves technique, for up to 3 weeks. At 18 hours, acute hyperpermeability was measured with 125I‐albumin, and cytokines and myeloperoxidase activity, a marker of neutrophils, were assayed in synovial fluid extracts. The possibility that exogenous tumor necrosis factor α (TNFα) was involved in influencing TRPV1 activation was investigated in separate experiments.

Results

Increased levels of knee swelling, hyperpermeability, leukocyte accumulation, and TNFα were found in WT mice 18 hours after IA CFA treatment compared with saline treatment. Significantly less knee swelling and hyperpermeability were found in TRPV1−/− mice, but leukocyte accumulation and TNFα levels were similar in WT and TRPV1−/− mice. Knee swelling in response to CFA remained significantly higher for a longer period in WT mice compared with TRPV1−/− mice, with thermal hyperalgesic sensitivity observed at 24 hours and at 1 week in WT, but not TRPV1−/−, mice. Knee swelling was attenuated (P < 0.05) in TRPV1−/− compared with WT mice 4 hours after IA administration of TNFα.

Conclusion

Our findings indicate that TRPV1 has a role in acute and chronic inflammation in the mouse knee joint. Thus, selective antagonism of TRPV1 should be considered as a potential target for treatment of acute and chronic joint inflammation.
Pathogenic role of the CXCL16–CXCR6 pathway in rheumatoid arthritis
Authors: Nanki Toshihiro , Shimaoka Takeshi , Hayashida Kenji , Taniguchi Ken , Yonehara Shin , Miyasaka Nobuyuki
Published: September 2005

Objective

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with massive T cell infiltration into the synovium. The accumulated T cells express type 1 cytokines, such as interferon‐γ (IFNγ) and tumor necrosis factor α, and activated markers of inflammation, such as CD154 and inducible costimulator (ICOS). It is thought that chemokines contribute to T cell accumulation in the synovium. In this study, we examined the role of CXCL16 and CXCR6 in T cell migration and stimulation in RA synovium.

Methods

Expression of CXCL16 and CXCR6 was analyzed by immunohistochemistry, reverse transcription–polymerase chain reaction, Western blotting, and/or flow cytometry. Migration activity was assessed using a chemotaxis chamber. IFNγ production was analyzed by enzyme‐linked immunosorbent assay. The effect of anti‐CXCL16 monoclonal antibody on murine collagen‐induced arthritis (CIA) was evaluated.

Results

CXCL16 was expressed in RA synovium. CXCR6 was expressed more frequently on synovial T cells than in peripheral blood. Moreover, CXCR6‐positive synovial T cells more frequently expressed CD154 and ICOS than did CXCR6‐negative T cells. Stimulation with interleukin‐15 (IL‐15) up‐regulated the expression of CXCR6 on peripheral blood T cells, and then stimulation with CXCL16 induced migration of IL‐15–stimulated T cells and enhanced IFNγ production. Furthermore, anti‐CXCL16 monoclonal antibody significantly reduced the clinical arthritis score and reduced infiltration of inflammatory cells and bone destruction in the synovium of mice with CIA.

Conclusion

Our results indicate that CXCL16 plays an important role in T cell accumulation and stimulation in RA synovium and suggest that CXCL16 could be a target molecule in new therapies for RA.
Association of HLA–DR3 with anti–cyclic citrullinated peptide antibody–negative rheumatoid arthritis
Authors: Verpoort Kirsten N. , van Gaalen Floris A. , van der Helm‐van Mil Annette H. M. , Schreuder Geziena M. T. , Breedveld Ferdinand C. , Huizinga Tom W. J. , de Vries Rene R. P. , Toes Rene E. M.
Published: September 2005

Objective

Recent data have shown that the most prominent and longest known genetic risk factors for rheumatoid arthritis (RA), HLA–DRB1 shared epitope alleles, are only associated with RA that is characterized by the presence of antibodies against cyclic citrullinated peptide (anti‐CCP antibodies) and not with anti‐CCP–negative RA. We undertook this study to investigate whether anti‐CCP–negative RA is associated with other HLA–DRB1 alleles.

Methods

HLA typing was performed for 377 patients from the Leiden Early Arthritis Clinic who were diagnosed as having RA within the first year of followup (206 anti‐CCP–positive patients and 171 anti‐CCP–negative patients), 235 patients who, after 1 year, had undifferentiated arthritis (UA) (28 anti‐CCP–positive patients and 207 anti‐CCP–negative patients), and 423 healthy control subjects. Odds ratios (ORs) with 95% confidence intervals (95% CIs) for HLA–DRB1 allele frequencies were determined for all patient groups compared with the healthy control group.

Results

HLA–DR3 was more frequently present in the anti‐CCP–negative RA group than in the control group (OR 1.84, 95% CI 1.26–2.67). This was not the case for anti‐CCP–positive RA (OR 0.92, 95% CI 0.60–1.40). HLA–DR3 was also more frequently present in anti‐CCP–negative UA patients (OR 1.59, 95% CI 1.10–2.28), but not in anti‐CCP–positive UA patients (OR 0.68, 95% CI 0.17–1.92).

Conclusion

HLA–DR3 is associated with anti‐CCP–negative arthritis and not with anti‐CCP–positive arthritis. These data show that distinct genetic risk factors are associated with the presence of anti‐CCP antibodies in RA and indicate that different pathogenetic mechanisms underlie anti‐CCP–positive and anti‐CCP–negative RA.
Blockade of lymphotoxin pathway exacerbates autoimmune arthritis by enhancing the Th1 response
Authors: Han Shuhua , Zhang Xuejun , Marinova Ekaterina , Ozen Zeynep , Bheekha‐Escura Roy , Guo Linjie , Wansley Daniel , Booth George , Fu Yang‐Xin , Zheng Biao
Published: September 2005

Objective

To study the role of the lymphotoxin (LT) signaling pathway in the development and pathogenesis of collagen‐induced arthritis (CIA), and to understand the mechanisms by which blockade of the LT pathway influences the arthritogenic response to type II collagen (CII).

Methods

LTα‐deficient and wild‐type C57BL/6 mice were immunized with CII. Male DBA/1 mice were immunized with CII and treated with LTβ receptor immunoglobulin fusion protein (LTβR‐Ig) or control Ig. Mice were monitored for the development and severity of arthritis. The effects of LT blockade on immune responses were evaluated by cytokine production and antigen‐specific proliferation in vitro, the delayed‐type hypersensitivity (DTH) response, and serum levels of CII‐specific antibodies.

Results

CIA that developed in LTα‐deficient mice was more severe and prolonged than that which developed in wild‐type mice. Blocking LT signaling with LTβR‐Ig significantly exacerbated the disease. Exacerbation of CIA was associated with an enhanced Th1‐type response, including increased type 1 cytokine production, an enhanced DTH response, and elevated production of CII‐specific IgG2a antibodies.

Conclusion

Blockade of the LT signaling pathway exacerbates the development and progression of CIA, probably by skewing the Th1/Th2 balance that determines the outcome of autoimmune responses.
Interleukin‐17 receptor deficiency results in impaired synovial expression of interleukin‐1 and matrix metalloproteinases 3, 9, and 13 and prevents cartilage destruction during chronic reactivated streptococcal cell wall–induced arthritis
Authors: Koenders Marije I. , Kolls Jay K. , Oppers‐Walgreen Birgitte , Van Den Bersselaar Liduine , Joosten Leo A. B. , Schurr Jill R. , Schwarzenberger Paul , Van Den Berg Wim B. , Lubberts Erik
Published: September 2005

Objective

To examine the role of interleukin‐17 receptor (IL‐17R) signaling in cartilage destruction and its interrelationship with synovial IL‐1 expression during chronic reactivated streptococcal cell wall (SCW)–induced arthritis.

Methods

SCW arthritis was repeatedly induced in wild‐type (WT) and IL‐17R–deficient (IL‐17R–/–) mice. At different time points, joint inflammation was assessed by using calipers to measure joint swelling. On day 42, mice were killed, and knee joints were removed for histologic analysis. Quantitative polymerase chain reaction (PCR) analyses for different proinflammatory mediators and matrix metalloproteinases (MMPs) were performed on inflamed synovium from WT and IL‐17R–/– mice after 5 repeated injections of SCW fragments.

Results

IL‐17R signaling did not play a significant role in acute joint swelling induced by a single injection of SCW fragments directly into the joint. However, repeated local injections of SCW fragments into the knee joints of IL‐17R–/– mice resulted in fewer infiltrating cells in the joint compared with WT mice. Moreover, histologic analysis on day 42 revealed a significant suppression of the degree of chondrocyte death and an absence of cartilage surface erosion in IL‐17R–/– mice. Quantitative PCR analysis revealed impaired synovial expression of IL‐1, IL‐6, cyclooxygenase 2, stromelysin (MMP‐3), gelatinase B (MMP‐9), and collagenase 3 (MMP‐13) in IL‐17R–/– mice.

Conclusion

These data show a critical role of IL‐17R signaling in driving the synovial expression of proinflammatory and catabolic mediators, such as IL‐1 and different MMPs, during progression from an acute, macrophage‐driven joint inflammation to a chronic, cartilage‐destructive, T cell–mediated synovitis. Prevention of IL‐17R signaling warrants consideration as a therapeutic target in chronic destructive arthritis.
Use of the plasma stromelysin (matrix metalloproteinase 3) concentration to predict joint space narrowing in knee osteoarthritis
Authors: Lohmander L. Stefan , Brandt Kenneth D. , Mazzuca Steven A. , Katz Barry P. , Larsson Staffan , Struglics André , Lane Kathleen A.
Published: September 2005

Objective

To determine whether baseline or serial plasma concentrations of stromelysin (matrix metalloproteinase 3 [MMP‐3]) protein might distinguish subjects with progressive radiographic knee osteoarthritis (OA) from those with stable disease.

Methods

Subjects were 120 women with unilateral knee OA who participated in a 30‐month randomized, placebo‐controlled trial of structure modification with doxycycline. Anteroposterior views of both knees in a semiflexed position were obtained at baseline, 16 months, and 30 months. Subjects were selected to obtain comparisons of plasma MMP‐3 levels between 60 progressors (21 taking doxycycline, 39 taking placebo) and 60 nonprogressors (30 taking doxycycline, 30 taking placebo) with respect to medial joint space narrowing (JSN) in the index knee. Each group consisted of 30 subjects who exhibited significant increases in knee pain. Blood samples were obtained semiannually for MMP‐3 assay.

Results

Subjects in the placebo group whose MMP‐3 concentration was in the upper tertile of the baseline distribution showed a 4‐fold increase in the odds of progression of JSN as compared with the lower tertile (odds ratio 4.12, P = 0.037). Baseline MMP‐3 levels were unrelated to knee pain. The within‐subject mean of serial MMP‐3 concentrations was associated with concurrent JSN in the placebo group over the 0–16‐month interval (b = 0.18 mm/SD increase in the mean MMP‐3, P < 0.01) and over the 16–30‐month interval (b = 0.15, P < 0.05). Similar evidence of concurrent validity was found in the placebo group for the maximum of intercurrent MMP‐3 values.

Conclusion

The baseline MMP‐3 level was a significant predictor of JSN in this pilot study. Moreover, serial plasma MMP‐3 levels reflected concurrent JSN in the placebo group over the 30‐month period of observation.
B lymphocyte depletion therapy in children with refractory systemic lupus erythematosus
Authors: Marks Stephen D. , Patey Sue , Brogan Paul A. , Hasson Nathan , Pilkington Clarissa , Woo Patricia , Tullus Kjell
Published: September 2005

Objective

To determine the safety and efficacy of B lymphocyte depletion therapy in patients with refractory childhood‐onset systemic lupus erythematosus (SLE).

Methods

Seven patients (4 of whom were female), ages 7.7–16.1 years (median 14.8 years) with active SLE that was resistant to standard immunosuppressive agents were treated with B cell depletion. During a 2‐week period, patients received two 750‐mg/m2 intravenous infusions of rituximab, with intravenous cyclophosphamide (if they had not previously received this treatment) and high‐dose oral corticosteroids.

Results

Patients were followed up for a median of 1.0 years, and no serious adverse effects were noted. In all patients, the clinical symptoms and signs for which rituximab therapy was initiated were improved. There was significant improvement in the British Isles Lupus Assessment Group global scores, from a median score of 22 (range 14–37) at baseline to a median score of 6 (range 4–11) at followup (P = 0.002). In 2 patients with severe multisystem and life‐threatening disease unresponsive to standard therapy (including plasma exchange), renal replacement therapy was successfully withdrawn following B cell depletion therapy. These 2 patients have subsequently shown further significant improvement in renal function and proteinuria.

Conclusion

This open‐label study demonstrates that targeted B cell depletion therapy can be a safe and efficacious addition to therapy with standard immunosuppressive agents in patients with refractory childhood SLE. The drugs used for treatment of childhood SLE need to be the most effective, least toxic agents, allowing normal growth and development.
A newly described hereditary cartilage debonding syndrome
Authors: Holderbaum D. , Malvitz T. , Ciesielski C. J. , Carson D. , Corr M. P. , Moskowitz R. W.
Published: September 2005

Objective

We describe a hereditary chondropathy characterized by extreme cartilage friability and cartilage–bone debonding, which has not previously been described in the literature. We also describe initial studies into the molecular basis of this disorder.

Methods

Affected family members had multiple shoulder, hip, and knee arthropathies, beginning in the preteen years and continuing into adulthood. Various diagnoses had been suggested, including spondyloepiphyseal dysplasia, multiple epiphyseal dysplasia, Legg‐Calvé‐Perthes disease, and Osgood‐Schlatter disease. The affected proband father, his 3 affected children, and unaffected family members provided blood samples, which were examined for single‐nucleotide polymorphisms (SNPs) in the chromosome 2 region that included the Frizzled‐related protein gene, a soluble Wnt protein signaling antagonist that influences bone and cartilage development.

Results

All affected individuals showed clear similarities, including effusions, large loose bodies, and bubbling and delamination of the cartilage with exposure of subchondral bone. All affected individuals exhibited radiographic changes in the hip, showing femoral head flattening and secondary degenerative arthritis, accompanied by abnormalities in the physical properties of the cartilage that were evident upon arthroscopic examination. Two SNPs were identified in subjects with the hereditary cartilage debonding syndrome. Examination of the siblings and parents of the proband demonstrated, however, that both SNPs were present in the unaffected mother and in 2 of 4 unaffected siblings of the proband.

Conclusion

The clinical findings reported here represent a newly defined clinical syndrome characterized by marked cartilage friability and osteochondral debonding. Because the SNPs are present in the general population, and because unaffected members of this family carry the SNPs, these polymorphisms alone are insufficient to result in the observed phenotype.
Synovial fibroblasts promote osteoclast formation by RANKL in a novel model of spontaneous erosive arthritis
Authors: Wu Yalei , Liu Jianzhong , Feng Xu , Yang PingAr , Xu Xin , Hsu Hui‐Chen , Mountz John D.
Published: September 2005

Objective

Erosion of cartilage and bone is a hallmark of rheumatoid arthritis (RA). This study was undertaken to explore the roles of hyperproliferating synovial fibroblasts and macrophages in abnormal osteoclast formation, using the recently described BXD2 mouse model of RA.

Methods

Cell distribution in the joints was analyzed by immunohistochemistry, using tartrate‐resistant acid phosphatase (TRAP) staining to identify osteoclasts. To identify the defective cells in BXD2 mice, mouse synovial fibroblasts (MSFs) were cultured with bone marrow–derived macrophages. Osteoclast formation was assayed by TRAP staining and bone resorption pit assay, and the cytokine profiles of the MSFs and macrophages were determined by quantitative real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay.

Results

In BXD2 mice, TRAP‐positive osteoclasts were found at sites of active bone erosion, in close proximity to hyperproliferating synovial fibroblasts. On coculture, MSFs from BXD2 mice, but not C57BL/6 mice, produced high levels of RANKL messenger RNA, induced macrophages to form osteoclasts, and actively eroded bone slices, through a mechanism(s) that could be blocked by pretreatment with osteoprotegerin. Although macrophages from BXD2 mice expressed higher basal levels of tumor necrosis factor α (TNFα), interleukin‐1β (IL‐1β), and IL‐6 than those from C57BL/6 mice, abnormal osteoclast formation was not due to enhanced sensitivity of the BXD2 mouse macrophages to RANKL. TNFα, produced by both BXD2 MSFs and BXD2 mouse macrophages, had a strong stimulatory effect on RANKL expression.

Conclusion

BXD2 MSFs produce RANKL and induce the development of osteoclasts from macrophages. The enhanced production of RANKL is possibly due to autocrine stimulation, together with paracrine stimulation by factors produced by macrophages.
Double‐blind, randomized, controlled clinical trial of clofazimine compared with chloroquine in patients with systemic lupus erythematosus
Authors: Bezerra Elaine Lira Medeiros , Vilar Maria José Pereira , da Trindade Neto Pedro Bezerra , Inoue Sato Emı´lia
Published: September 2005

Objective

To evaluate the efficacy of clofazimine (CFZ) compared with chloroquine diphosphate (CDP) for the treatment of cutaneous involvement in systemic lupus erythematosus (SLE).

Methods

A prospective, randomized, controlled, double‐blind clinical trial was carried out in SLE patients with active cutaneous lesions, of whom 16 were randomized to receive CFZ at 100 mg/day and 17 received CDP at 250 mg/day for 6 months. All drugs had a similar appearance to avoid identification. Both groups received broad‐spectrum sunscreens twice a day and the prednisone dose was kept stable during the study. Cutaneous lesions were evaluated by 2 blinded observers at baseline and at months 1, 2, 4, and 6.

Results

Thirty‐three patients were randomized to a treatment group, of whom 27 completed 6 months of treatment. The groups were homogeneous and comparable in terms of demographic and clinical characteristics. Five CFZ‐treated patients and 1 CDP‐treated patient (P = 0.15) dropped out due to development of severe lupus flare. At the end of the study, 12 CFZ‐treated patients (75%) and 14 CDP‐treated patients (82.4%) had complete or near‐complete remission of skin lesions; intention‐to‐treat analysis showed no significant difference in the response rates between groups. Side effects, mainly skin and gastrointestinal events, were frequent in both groups, but no patients had to discontinue their treatment.

Conclusion

These findings suggest that CFZ is equally as effective as CDP in controlling cutaneous lesions in SLE patients. However, we cannot exclude the possibility that the CFZ itself could be the cause of systemic lupus flare.
Investigating the Anomalous States of Knowledge hypothesis in a real‐life problem situation: A study of history and psychology undergraduates seeking information for a course essay
Authors: Cole Charles , Leide John , Beheshti Jamshid , Large Andrew , Brooks Martin
Published: September 2005

The authors present a study of the real‐life information needs of 59 McGill University undergraduates researching essay topics for either a history or psychology course, interviewed just after they had selected their essay topic. The interview's purpose was to transform the undergraduate's query from general topic terms, based on vague conceptions of their essay topic, to an information need‐based query. To chart the transformation, the authors investigate N. J. Belkin, R. N. Oddy, and H. M. Brooks' Anomalous States of Knowledge (ASK) hypothesis (1982a, 1982b), which links the user's ASK to a relevant document set via a common code based on structural facets. In the present study an interoperable structural code based on eight essay styles is created, then notions of structural facets compatible with a high‐impact essay structure are presented. The important findings of the study are: (a) the undergraduates' topic statements and terms derived from it do not constitute an effective information need statement because for most of the subjects in the study the topic terms conformed to a low‐impact essay style; (b) essay style is an effective interoperable structural code for charting the evolution of the undergraduate's knowledge state from ASK to partial resolution of the ASK in an information need statement.
The use of multi‐parameter flow cytometry to study the impact of limiting substrate, agitation intensity, and dilution rate on cell aggregation during Bacillus licheniformis CCMI 1034 aerobic continuous culture fermentations
Authors: da Silva Teresa Lopes , Reis Alberto , Kent Christopher A. , Roseiro J. Carlos , Hewitt Christopher J.
Published: September 2005

The main objective of this work was to establish those factors either physical (power input) or chemical (limiting substrate or dilution rate) that enhance cell aggregation (biofilm or floc formation) and cell physiological state during aerobic continuous cultures of Bacillus licheniformis. Glucose‐limited steady‐state continuous cultures growing at a dilution rate between 0.64 and 0.87/h and 1,000 rpm (mean specific energy dissipation rate ($\bar {\varepsilon} _T$) = 6.5 W/kg), led to the formation of a thin biofilm on the vessel wall characterized by the presence of a high proportion of healthy cells in the broth (after aggregate disruption by sonication) defined as having intact polarized cytoplasmic membranes. An increased $\bar {\varepsilon} _T$ (from 6.5 W/kg to 38 W/kg) was found to hinder cell aggregation under carbon limitation. The carbon recovery calculated from glucose indicated that additional extracellular polymer was being produced at dilution rates >0.87/h. B. licheniformis growth under nitrogen limitation led to floc formation which increased in size with dilution rate. Counter‐intuitively the flocs became more substantial with an increase in $\bar {\varepsilon} _T$ from 6.5 W/kg to 38 W/kg under nitrogen limitation. Indeed the best culture conditions for enhanced metabolically active cell aggregate formation was under nitrogen limitation at $\bar {\varepsilon} _T$ = 6.5 W/kg (leading to floc formation), and under carbon limitation at a dilution rate of between 0.64 and 0.87/h, at $\bar {\varepsilon} _T$ = 6.5 W/kg (leading to vessel wall biofilm formation). This information could be used to optimize culture conditions for improved cell aggregation and hence biomass separation, during thermophilic aerobic bioremediation processes. © 2005 Wiley Periodicals, Inc.
A simple and reliable method for the detection of sialylation in complex/hybrid‐type carbohydrate chains of glycoproteins by mixed lectins
Authors: Natsuki Jun , Machida Masayuki
Published: September 2005

A practical and convenient method for discriminating between the presence and the absence of sialic acid in carbohydrate chains of glycoproteins was devised using paramagnetic beads and two lectins, Sambucus sieboldiana lectin (SSA) and Ricinus communis agglutinin (RCA120). The glycoproteins of transferrin or thyroglobulin were firstly captured to paramagnetic beads that were previously coated with corresponding antibody, and then the lectins of RCA120‐biotin and SSA‐FITC were bound to the glycoproteins on the paramagnetic beads. Finally, the fluorescence intensity of the beads was measured to determine the ratios of lectins RCA120‐biotin/Cy5‐streptavidin to SSA‐FITC. The mixed lectins method showed bigger difference of the ratios between the presence and the absence of sialic acid, indicating higher discrimination efficiency than the ordinary non‐mixed lectins method. Furthermore, statistical analysis by two‐side t‐test indicated that the mixed lectins method was more highly reliable than the ordinary non‐mixed lectins method in discriminating between the presence and the absence of sialic acid. The reaction with the two lectins can be performed in a single tube and readily automated taking advantage of the use of paramagnetic beads. © 2005 Wiley Periodicals, Inc.