bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genetic contribution to muscle strength, knee pain, cartilage volume, bone size, and radiographic osteoarthritis: A sibpair study
Authors: Zhai Guangju , Stankovich James , Ding Changhai , Scott Fiona , Cicuttini Flavia , Jones Graeme 
Published: March 2004

AbstractObjectiveTo estimate the heritability of muscle strength, knee pain, cartilage volume, bone size, and radiographic osteoarthritis (ROA), and to assess whether heritability of the knee structural components is independent of ROA.MethodsA sibpair design was utilized. Sagittal T1‐weighted fat‐suppressed magnetic resonance imaging (MRI) of the right knee was performed to determine cartilage volume and bone size. Standing semiflexed radiographs of the same knee were obtained to assess the presence of ROA. Knee pain was assessed by questionnaire and muscle strength by dynamometry. Heritability was estimated using the genetic analysis program SOLAR.ResultsA total of 128 subjects (61 men, 67 women; mean age 45 years) from 51 families representing 115 sibpairs were studied. Lower limb muscle strength had high heritability (42%; P = 0.02), as did knee pain (44%; P = 0.07). Heritability estimates for cartilage volume were 65% for medial tibial cartilage, 77% for lateral tibial cartilage, and 84% for patellar cartilage, and heritability estimates for bone size were 85% for medial tibial bone area, 57% for lateral tibial bone area, and 70% for patella bone volume (all P ≤ 0.004). For ROA, heritability was 61% for presence (with a large standard error) (P = 0.16) and 61% for severity (P = 0.02). The estimates for tibial bone areas were the only ones markedly reduced after adjustment for body size, while all estimates with the exception of knee pain were independent of ROA. Cartilage and, to a lesser extent, bone sites investigated by MRI were largely under independent genetic control, with a lesser shared genetic component.ConclusionWith the exception of prevalent ROA, all knee modalities assessed had high heritability, most likely reflecting a strong genetic component. Cartilage volume, bone size, and muscle strength all have the potential to be studied in quantitative trait linkage analyses, but their exact relevance with regard to OA remains uncertain at this time.
Tumor necrosis factor receptor II gene polymorphism and severity of rheumatoid arthritis
Authors: Constantin Arnaud , Dieudé Philippe , Lauwers‐Cancès Valérie , Jamard Bénédicte , Mazières Bernard , Cambon‐Thomsen Anne , Cornélis François , Cantagrel Alain 
Published: March 2004

AbstractObjectiveThe gene encoding tumor necrosis factor receptor type II (TNFRII) is a strong candidate in the pathogenesis of rheumatoid arthritis (RA). An association between a single‐nucleotide polymorphism (196M/R) in exon 6 of the TNFRII gene and familial RA was recently reported. The present study was undertaken to test the hypothesis that there is an association between this polymorphism and the severity of RA.MethodsOne hundred two white patients with early RA were included in this prospective study. The French version of the Health Assessment Questionnaire (F‐HAQ) and a radiographic damage score (modified Sharp/van der Heijde method) were used to quantify the functional and structural severity of RA at baseline and after 4 years of followup. TNFRII 196M/R polymorphism genotyping was performed by polymerase chain reaction–restriction fragment length polymorphism analysis.ResultsAmong the 102 patients with RA, 63 (61.8%) were homozygous for the 196M allele, 36 (35.3%) were heterozygous for alleles 196M and 196R, and 3 (2.9%) were homozygous for the 196R allele. At baseline, the median radiographic and F‐HAQ scores did not differ between RA patients who carried the 196R allele and those who did not. After 4 years of followup, the F‐HAQ score was higher in RA patients carrying the 196R allele (median 1 [interquartile range (IQR) 0.125, 1.375]) than in noncarriers (0.375 [IQR 0, 1]) (P = 0.02), while the median radiographic score did not differ between RA patients who carried the 196R allele and those who did not.ConclusionThe results of the present study support the hypothesis that there is an association between the TNFRII 196 M/R gene polymorphism and the functional severity of early RA.
Lack of association of the HLA–DRB1 shared epitope with rheumatoid nodules: An individual patient data meta‐analysis of 3,272 Caucasian patients with rheumatoid arthritis
Authors: Gorman Jennifer D. , David‐Vaudey Eve , Pai Madhukar , Lum Raymond F. , Criswell Lindsey A. 
Published: March 2004

AbstractObjectiveThe objective of this individual patient data (IPD) meta‐analysis was to examine the relationship of rheumatoid nodules to the HLA–DRB1 shared epitope (SE) and to individual SE genotypes.MethodsEnglish‐language studies that enrolled adult non‐Hispanic Caucasian patients with rheumatoid arthritis (RA) were identified by searches of Medline and Embase, and by manual searches of medical journals. All authors were contacted for IPD. Metaanalysis was performed to assess the association of SE presence, dose, and genotype with rheumatoid nodules. Meta‐analyses adjusted for disease duration and cumulative meta‐analyses were also performed to assess the influence of RA duration and year of study publication on the results.ResultsA total of 24 studies and 3,272 patients were available for analysis. IPD were obtained for 22 of the studies. There was a nonsignificant association between the presence of the SE (i.e., 1 or 2 alleles versus 0 alleles) and rheumatoid nodules (summary odds ratio [OR] 1.3, 95% confidence interval [95% CI] 0.97–1.6). Analysis by SE genotype, however, demonstrated a weak relationship with inheritance of a single DRB1*0401 SE allele (OR 1.4, 95% CI 1.1–1.8). No other genotypes achieved statistical significance in the adjusted or unadjusted analyses.ConclusionThe presence of the HLA–DRB1 SE does not appear to significantly increase the risk of rheumatoid nodules among Caucasian patients with RA. Analysis by DRB1 SE genotype was uninformative, suggesting only a potential (and at most modest) role of the DRB1*0401 SE allele. Results from this IPD meta‐analysis implicate other genetic, stochastic, and/or environmental factors in the susceptibility to rheumatoid nodules.
Quantitative assessment of cartilage status in osteoarthritis by quantitative magnetic resonance imaging: Technical validation for use in analysis of cartilage volume and further morphologic parameters
Authors: Graichen Heiko , Eisenhart‐Rothe Rüdiger v. , Vogl Thomas , Englmeier Karl‐Hans , Eckstein Felix 
Published: March 2004

AbstractObjectiveQuantitative diagnostic tools for osteoarthritis (OA) are important for evaluating the treatment response to structure‐modifying drugs. This study was undertaken to test the technical validity (accuracy) of quantitative magnetic resonance imaging (qMRI) for reliable determination of the total bone interface area, percentage of cartilaginous (denuded) joint surface area, and cartilage thickness in OA.MethodsHigh‐resolution MRIs of femorotibial and patellar cartilage were acquired in 21 patients prior to total knee arthroplasty, using a T1‐weighted gradient‐echo sequence with water excitation. After segmentation of original bone interface areas (before disease onset) and the actual cartilage layer, the percentages of cartilaginous joint surface area, cartilage thickness, and cartilage volume were determined using proprietary software. During surgery, the patella and the medial and lateral tibia were resected. Results obtained with qMRI were compared with those obtained by direct image analysis of surface area, cartilage thickness, and cartilage volume of the surgically removed tissue.ResultsPairwise differences between results obtained with qMRI and morphologic analysis were ±4.6% for percentage of cartilaginous surface area, ±8.9% for cartilage thickness, and ±9.1% for cartilage volume. Correlation coefficients ranged from 0.92 (thickness) to 0.98 (volume).ConclusionQuantitative MRI permits technically accurate and differential assessment of increases in eroded joint surface area and reductions in cartilage thickness in OA. The surrogate validity of these parameters requires testing in longitudinal studies. These parameters may be advantageous over determination of cartilage volume alone when diagnosing OA, exploring its progression, or testing responsiveness to new therapies.
Association of a four–amino acid residue insertion polymorphism of the HS1 gene with systemic lupus erythematosus: Molecular and functional analysis
Authors: Otsuka Junji , Horiuchi Takahiko , Yoshizawa Shigeru , Tsukamoto Hiroshi , Sawabe Takuya , Kikuchi Yuji , Himeji Daisuke , Koyama Takako , Mitoma Hiroki , Watanabe Takeshi , Harada Mine 
Published: March 2004

AbstractObjectiveTo investigate whether polymorphism(s) or mutation(s) in the hematopoietic cell–specific Lyn substrate 1 (HS1) gene are involved in the pathogenesis of systemic lupus erythematosus (SLE).MethodsThe entire coding region of the HS1 gene was analyzed by reverse transcriptase–polymerase chain reaction/single‐strand conformational polymorphism analysis. HS1‐transfected WEHI‐231 cells or B lymphocytes from patients with SLE were studied for apoptosis, activation, and proliferation by flow cytometric analysis and MTT assay.ResultsWe identified a glutamic acid–proline–glutamic acid–proline insertion between codons 366 and 367 (EPEP366–367ins) and 2 amino acid substitutions (A235T and E361K). The genotype frequency among individuals homozygous for the EPEP+ allele was 0.184 in 201 patients with SLE but only 0.098 in 184 healthy individuals (P = 0.016). The allele frequency of EPEP366–367ins was 0.408 in patients with SLE; this frequency was significantly higher than that in healthy controls (0.312) (P = 0.006). WEHI‐231 cells transfected with EPEP+ HS1 were 100‐fold more sensitive to B cell receptor (BCR)–mediated apoptosis than were those transfected with HS1 without EPEP. B lymphocytes from SLE patients with the EPEP+ allele were significantly more apoptotic without BCR stimulation and less activated after BCR stimulation than were those from SLE patients without the EPEP allele.ConclusionThese results suggest that HS1 with the EPEP insertion polymorphism transmits accelerated signals from BCR and is involved in the pathogenesis of SLE.
Suppression of T cell responses by chondromodulin I, a cartilage‐derived angiogenesis inhibitory factor: Therapeutic potential in rheumatoid arthritis
Authors: Setoguchi Keigo , Misaki Yoshikata , Kawahata Kimito , Shimada Kota , Juji Takuo , Tanaka Sakae , Oda Hiromi , Shukunami Chisa , Nishizaki Yuriko , Hiraki Yuji , Yamamoto Kazuhiko 
Published: March 2004

AbstractObjectiveChondromodulin I (ChM‐I), a cartilage matrix protein, promotes the growth and proteoglycan synthesis of chondrocytes. However, it also inhibits angiogenesis. Since ChM‐I is expressed not only in cartilage, but also in the thymus, we investigated the modulation of T cell function by ChM‐I to assess its therapeutic potential in rheumatoid arthritis (RA).MethodsThe localization of ChM‐I expression in mouse thymus tissue was examined by in situ hybridization. The proliferative response of peripheral blood T cells and synovial cells obtained from patients with RA was evaluated by 3H‐thymidine incorporation assay. The effects of ChM‐I were examined using recombinant human ChM‐I (rHuChM‐I). Modulation of the antigen‐specific immune response was evaluated by the recall response of splenic T cells and the delayed‐type hypersensitivity response induced in the ear of mice primed with ovalbumin (OVA). Antigen‐induced arthritis (AIA) was induced in mice by injecting methylated bovine serum albumin into the ankle joints 2 weeks after the priming.ResultsChM‐I was expressed in the cortex of the thymus. Recombinant human ChM‐I suppressed the proliferative response of mouse splenic T cells and human peripheral blood T cells stimulated with anti‐CD3/CD28 antibodies, in a dose‐dependent manner. Production of interleukin‐2 was decreased in rHuChM‐I–treated mouse CD4 T cells. Ten micrograms of rHuChM‐I injected intraperitoneally into OVA‐primed mice suppressed the induction of the antigen‐specific immune response. Finally, rHuChM‐I suppressed the development of AIA, and also suppressed the proliferation of synovial cells prepared from the joints of patients with RA.ConclusionThese results suggest that ChM‐I suppresses T cell responses and synovial cell proliferation, implying that this cartilage matrix protein has a therapeutic potential in RA.
Quantification of maternal microchimerism by HLA‐specific real‐time polymerase chain reaction: Studies of healthy women and women with scleroderma
Authors: Lambert Nathalie C. , Erickson Timothy D. , Yan Zhen , Pang Jennifer M. , Guthrie Katherine A. , Furst Daniel E. , Nelson J. Lee 
Published: March 2004

AbstractObjectiveMicrochimerism (Mc), originating from bidirectional fetal–maternal cell traffic during pregnancy, has recently been identified in healthy adults and in patients with scleroderma (systemic sclerosis [SSc]). This study was undertaken to investigate the frequency and quantitative levels of maternal Mc (MMc) in healthy women and women with SSc.MethodsHLA‐specific primers and fluorogenic probes were used in real‐time quantitative polymerase chain reaction assays to detect and quantify MMc by targeting noninherited, nonshared HLA sequences. DNA‐based HLA typing was conducted in 67 proband‐mother pairs and in all children if the proband was parous. Statistical analysis was limited to 50 proband‐mother pairs (including 32 healthy women and 18 women with SSc) in whom MMc could be distinguished from potential fetal Mc.ResultsMMc in peripheral blood mononuclear cells was more frequent among women with SSc (72%) than healthy women (22%) (odds ratio 9.3,P= 0.001). However, levels of MMc, expressed as the genome equivalent of maternal cells per million (gEq/mil), were not significantly different (0–68.6 gEq/mil in SSc patients, 0–54.5 in healthy women). In additional studies, positivity for MMc was demonstrated in a bone marrow aspirate from an SSc patient in whom peripheral blood had been found to be negative for MMc on 4 occasions, and tissue from a subsequent autopsy of this patient had MMc levels of 757 and 1,489 gEq/mil in the lung and heart, respectively.ConclusionMMc is not uncommon in the peripheral blood of healthy adults, is increased in frequency in patients with SSc, and may be present in bone marrow and disease‐affected tissues although absent in the peripheral blood.
Modulation of inflammation and response to dexamethasone by Annexin 1 in antigen‐induced arthritis
Authors: Yang Yuan H. , Morand Eric F. , Getting Stephen J. , Paul‐Clark Mark , Liu Dong L. , Yona Simon , Hannon Robert , Buckingham Julia C. , Perretti Mauro , Flower Roderick J. 
Published: March 2004

AbstractObjectiveAnnexin 1 (Anx‐1) is a putative mediator of the antiinflammatory actions of glucocorticoids (GCs). This study investigated the role of Anx‐1 in experimental arthritis and in GC‐mediated inhibition of inflammation, using antigen‐induced arthritis (AIA) in Anx‐1 knockout (Anx‐1−/−) mice.MethodsArthritis was induced by intraarticular injection of methylated BSA (mBSA) in mice preimmunized with mBSA. Disease was assessed after 7 days by histologic examination of the knee joints. Serum levels of anti‐mBSA IgG were determined by enzyme‐linked immunosorbent assay. Cytokine messenger RNA (mRNA) expression was detected by real‐time polymerase chain reaction.ResultsA significant exacerbation of arthritis was observed in the Anx‐1−/− mice compared with wild‐type (WT) mice. This was associated with increased mRNA expression of synovial interleukin‐1β, tumor necrosis factor α, interleukin‐6, and macrophage migration inhibitory factor. Dexamethasone significantly reduced the histologic severity of synovitis and bone damage in the WT mice, but exerted no inhibitory effects in the Anx‐1−/− mice, and also significantly reduced the serum levels of anti‐mBSA IgG and the numbers of peripheral blood neutrophils and lymphocytes in WT mice, but had no such effect in Anx‐1−/− mice.ConclusionAnx‐1 exerts endogenous antiinflammatory effects on AIA via the regulation of cytokine gene expression, and also mediates the antiinflammatory actions of dexamethasone in AIA.
The antirheumatic drug leflunomide inhibits osteoclastogenesis by interfering with receptor activator of NF‐κB ligand–stimulated induction of nuclear factor of activated T cells c1
Authors: Urushibara Makoto , Takayanagi Hiroshi , Koga Takako , Kim Sunhwa , Isobe Miho , Morishita Yasuyuki , Nakagawa Takumi , Löeffler Monika , Kodama Tatsuhiko , Kurosawa Hisashi , Taniguchi Tadatsugu 
Published: March 2004

AbstractObjectiveSuppression of bone destruction is required as part of an effective therapeutic strategy for autoimmune arthritis. Although numerous antirheumatic drugs are in clinical use, little is known about whether they inhibit bone destruction by acting on activated T cells or other cell types, such as bone‐resorbing osteoclasts. This study was undertaken to determine whether leflunomide has a direct action on the osteoclast lineage and to gain insights into the molecular basis for the bone‐protective effect of leflunomide.MethodsThe direct effect of leflunomide on osteoclast differentiation was investigated using an in vitro culture system of bone marrow monocyte/macrophages stimulated with receptor activator of NF‐κB ligand (RANKL) and macrophage colony‐stimulating factor. The molecular mechanism of the inhibition was analyzed by genome‐wide screening. The T cell–independent effect of leflunomide was examined in rag‐2−/− mice.ResultsLeflunomide blocked de novo pyrimidine synthesis and RANKL‐induced calcium signaling in osteoclast precursor cells in vitro; hence, the induction of nuclear factor of activated T cells c1 (NF‐ATc1) was strongly inhibited. The inhibition of this pathway is central to the action of leflunomide, since the inhibition was overcome by ectopic expression of NF‐ATc1 in the precursor cells. Leflunomide suppressed endotoxin‐induced inflammatory bone destruction even in rag‐2−/− mice.ConclusionLeflunomide has a direct inhibitory effect on RANKL‐mediated osteoclast differentiation by inhibiting the induction of NF‐ATc1, the master switch regulator for osteoclast differentiation. Our study suggests that the direct inhibitory action of leflunomide on osteoclast differentiation constitutes an important aspect in the amelioration of bone destruction, and that the RANKL‐dependent NF‐ATc1 induction pathway is a promising target for pharmacologic intervention in arthritic bone destruction.
Policy modes, firms and the natural environment
Authors: Prakash Aseem , Kollman Kelly 
Published: March 2004

AbstractThis paper examines how different environmental policy types differentially impact firms and why firms vary in their responses to such policies. Based on the mechanisms embedded in policy instruments to create incentives for firms to comply, the characteristics of benefits/costs that policies impose on firms and the institutional context in which policy instruments were created and are sustained, the paper identifies five policy categories. These are category I (command and control), category II (market based), category III (mandatory information disclosures), category IV (business–government partnerships) and category V (private voluntary codes). Different policy types often bestow asymmetrical benefits/costs on firms. Some benefits/costs may constitute ‘private/club goods’ while others may constitute ‘public goods’. Drawing insights from public policy literature, the paper argues that firms can be expected to favor policies whose benefits have the characteristics of private/club goods but the costs of public goods. Thus, understanding the nature of benefits/costs (private/club versus public) and the magnitude of their excludability is critical in explaining the variations in firms' responses. To understand how managers perceive the nature of benefits/costs (monetary as well as non‐monetary), the paper draws on theories and perspectives in the business and public policy field. In doing so, the paper examines the ‘demand’ and the ‘supply’ sides as well as the market and non‐market environments of a given policy. Thus, the paper makes a case for a multi‐theoretic approach to understand variations in managerial assessments of benefits/costs, and consequently variations in their responses to various policy types. Copyright © 2004 John Wiley & Sons, Ltd and ERP Environment.
Environmental accounting: an essential component of business strategy
Authors: Yakhou Mehenna , Dorweiler Vernon P. 
Published: March 2004

AbstractEnvironmental accounting is on an expansion path. With increasing social focus on the environment, accounting fills an expectation role, to measure environmental performance. The status of environmental awareness provides a dynamic for business reporting its environmental performance. Examining the integration of environmental policy with business policy is the focus of this research. The business firm's strategy includes responding to capital and operating costs of pollution control equipment. This is caused by increasing public concerns over environmental issues, and by a recent government‐led trend to incentive‐based regulation. This paper describes the environmental component of the business strategy, producing the required performance reports and recognizing the multiple skills required to measure, compile and analyze the requisite data. Special emphasis of the research is on generation of reports and their standards, for the range of business and regulatory purposes. Copyright © 2004 John Wiley & Sons, Ltd and ERP Environment.
Can ‘market transformation’ lead to ‘sustainable business’? A critical appraisal of the UK's strategy for sustainable business
Authors: Smallbone Teresa 
Published: March 2004

AbstractThis paper traces the origins and development of the concept of ‘market transformation’, from its beginnings as a part of energy policy in the USA, to its subsequent development in the UK. It discusses whether it could become a strategic option for British business in pursuit of sustainable growth. Drawing together themes from the academic literature on marketing, consumer behaviour, business, and energy policy, together with data from national programmes, and British government sources, the paper argues that such an approach would be based on a twin false premise – that selling energy efficiency to consumers is in accordance with modern marketing thinking, and that it has much to do with achieving sustainable development. It concludes that while achieving sustainable development will certainly encompass the transformation of markets for many products, ‘market transformation’ itself cannot be seen as a key driver for change. Copyright © 2004 John Wiley & Sons, Ltd and ERP Environment.