bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cartilage‐like gene expression in differentiated human stem cell spheroids: A comparison of bone marrow–derived and adipose tissue–derived stromal cells
Authors: Winter Anja , Breit Stephen , Parsch Dominik , Benz Karin , Steck Eric , Hauner Hans , Weber Renate M. , Ewerbeck Volker , Richter Wiltrud 
Published: February 2003

AbstractObjectiveTo compare the chondrogenic potential of human bone marrow–derived mesenchymal stem cells (BMSC) and adipose tissue–derived stromal cells (ATSC), because the availability of an unlimited cell source replacing human chondrocytes could be strongly beneficial for cell therapy, tissue engineering, in vitro drug screening, and development of new therapeutic options to enhance the regenerative capacity of human cartilage.MethodsQuantitative gene expression of common cartilage and cell interaction molecules was analyzed using complementary DNA array technology and reverse transcription–polymerase chain reaction during optimization of cell differentiation, in order to achieve a molecular phenotype similar to that of chondrocytes in cartilage.ResultsThe multilineage potential of BMSC and ATSC was similar according to cell morphology and histology, but minor differences in marker gene expression occurred in diverse differentiation pathways. Although chondrogenic differentiation of BMSC and ATSC was indistinguishable in monolayer and remained partial, only BMSC responded (with improved chondrogenesis) to a shift to high‐density 3‐dimensional cell culture, and reached a gene expression profile highly homologous to that of osteoarthritic (OA) cartilage.ConclusionHypertrophy of chondrocytes and high matrix‐remodeling activity in differentiated BMSC spheroids and in OA cartilage may be the basis for the strong similarities in gene expression profiles between these samples. Differentiated stem cell spheroids represent an attractive tool for use in drug development and identification of drug targets in OA cartilage–like tissue outside the human body. However, optimization of differentiation protocols to achieve the phenotype of healthy chondrocytes is desired for cell therapy and tissue engineering approaches.
Immature articular cartilage is more susceptible to blood‐induced damage than mature articular cartilage: An in vivo animal study
Authors: Hooiveld Michel J. J. , Roosendaal Goris , Vianen Marieke E. , Van Den Berg H. Marijke , Bijlsma Johannes W. J. , Lafeber Floris P. J. G. 
Published: February 2003

AbstractObjectiveCartilage of young but skeletally mature dogs is more susceptible to blood‐induced damage than that of old dogs. The aim of the present study was to investigate whether cartilage of skeletally immature individuals is even more adversely affected by exposure to blood than that of mature individuals, as suggested by clinical practice experience with humans.MethodsRight knees of 3 groups of 6 beagle dogs (skeletally immature, young mature, and old animals) were injected with autologous blood on days 0 and 2. On day 4, cartilage matrix proteoglycan turnover (content, synthesis, and release), synovial inflammation, and cartilage‐destructive properties of the synovial tissue were determined and compared with those of the left uninjected control knees.ResultsSubsequent to intraarticular bleeding, cartilage proteoglycan content decreased in an age‐dependent manner, with the largest decrease occurring in cartilage of immature animals. Proteoglycan synthesis per cell also decreased in an age‐dependent manner, with the largest decrease occurring in the immature animals. Cartilage proteoglycan release increased in all 3 groups, but the decrease was not age dependent. Interestingly, immature animals showed a large increase in cartilage DNA content upon exposure to blood, whereas mature animals did not. Histologic analysis showed a mild synovitis in animals of all ages, but catabolic inflammatory activity was found only in immature animals.ConclusionJoints of skeletally immature dogs appeared to be more susceptible than joints of mature dogs to the adverse effects of a joint hemorrhage. These data suggest that for humans, specifically young children are at risk for joint damage after a joint hemorrhage.
Valine/valine genotype at position 247 of the β2‐glycoprotein I gene in Mexican patients with primary antiphospholipid syndrome: Association with anti–β2‐glycoprotein I antibodies
Authors: Prieto G. Aleph , Cabral Antonio R. , Zapata‐Zuñiga Martín , Simón Abraham J. , Villa Antonio R. , Alarcón‐Segovia Donato , Cabiedes Javier 
Published: February 2003

AbstractObjectiveTo determine the polymorphism at position 247 of the β2‐glycoprotein I (β2GPI) gene in Mexican patients with antiphospholipid syndrome (APS) and to compare these data in patients with or without antibodies to β2GPI and with the clinical manifestations of APS.MethodsWe studied 39 patients with primary APS and compared them with 106 clinically healthy subjects. Polymorphism was determined by polymerase chain reaction–restriction fragment length polymorphism. The presence of “true” anticardiolipin (aCL) antibodies, β2GPI‐dependent aCL antibodies (IgG and IgM), and phospholipid‐free anti‐β2GPI antibodies (IgG isotype) were detected by enzyme‐linked immunosorbent assay (ELISA) utilizing nonirradiated ELISA plates. Clinical manifestations associated with antiphospholipid antibodies were also evaluated.ResultsWe found no significant differences in the genotype expression between the control group and the primary APS patients (13% with VV, 52% with VL, and 35% with LL versus 23% with VV, 51% with VL, and 26% with LL, respectively). In contrast, anti‐β2GPI–positive patients had significantly higher frequencies of the VV genotype and V allele expression than the control subjects and the anti‐β2GPI–negative patients. These genotype and allele frequencies were also significantly higher in patients with arterial thrombosis than in patients without it. Anti‐β2GPI–negative patients without arterial thrombosis did not express the VV genotype. We found no differences in the Val/Leu247 polymorphism of the β2GPI gene in primary APS patients with or without “true” aCL antibodies or in primary APS patients with or without β2GPI‐dependent aCL antibodies.ConclusionOur results suggest that the VV genotype at position 247 of the β2GPI gene may play a role in the generation of anti‐β2GPI antibodies and perhaps in the expression of arterial thrombosis in primary APS.
Binding of outer surface protein A and human lymphocyte function–associated antigen 1 peptides to HLA–DR molecules associated with antibiotic treatment–resistant Lyme arthritis
Authors: Steere Allen C. , Falk Ben , Drouin Elise E. , Baxter‐Lowe Lee Ann , Hammer Juergen , Nepom Gerald T. 
Published: February 2003

AbstractObjectiveTo assess the binding of outer surface protein A (OspA) and human lymphocyte function–associated antigen 1 (hLFA‐1) peptides to 5 major histocompatibility complex (MHC) molecules.MethodsPeptide binding to the MHC molecules was determined by in vitro binding assays, and binding was correlated with the frequencies of the 5 MHC molecules in patients with treatment‐resistant Lyme arthritis.ResultsThe HLA–DRB1*0401 molecule bound both OspA163–175 and hLFA‐1αL330–342 well. Although the magnitude of the binding was less, the DRB1*0404 molecule also showed binding of both peptides. The DRB1*0101 molecule bound OspA163–175 well, but hLFA‐1αL330–342 only weakly; the DRB1*0801 or *1101 molecule bound both peptides weakly, if at all. The magnitude of OspA163–175 binding correlated well with the frequencies of the DRB1 alleles in patients with treatment‐resistant arthritis, but the binding of hLFA‐1αL330–342 showed only an association with the DRB*04 alleles.ConclusionThese correlations support the hypothesis that OspA163–175 is the critical epitope in triggering antibiotic treatment–resistant Lyme arthritis. However, the inability of the DRB*0101 molecule to bind hLFA‐1αL330–342 suggests that this peptide may not be a relevant autoantigen, at least in DRB1*0101‐positive patients.
Measurement of radiographic joint space width in the tibiofemoral compartment of the osteoarthritic knee: Comparison of standing anteroposterior and Lyon Schuss views
Authors: Vignon Eric , Piperno Muriel , Le Graverand Marie‐Pierre Hellio , Mazzuca Steven A. , Brandt Kenneth D. , Mathieu Pierre , Favret Huguett , Vignon Martine , Merle‐Vincent Florence , Conrozier Thierry 
Published: February 2003

AbstractObjectiveTo evaluate progression of joint space narrowing in radiographs of osteoarthritic (OA) knees imaged in both the standing anteroposterior (AP) and the Lyon schuss positions, using alternative methods to measure joint space width (JSW).MethodsStanding AP (extended view) and Lyon schuss (posteroanterior [PA] view, with 20–30° of flexion) radiographic images of 58 OA knees were obtained twice (at baseline and 2 years later). With both methods, fluoroscopy was used to align the anterior and posterior margins of the medial or lateral tibial plateau with the central x‐ray beam. Minimum JSW, mean JSW, and joint space area (JSA) of the medial or lateral femorotibial joint space were measured using a new digital image analysis system. The effects of knee flexion versus extension and parallel versus nonparallel tibial plateau alignment were evaluated with respect to the reproducibility of JSW in repeated examinations (intraclass correlation coefficient [ICC]), the mean of within‐knee standard deviations of repeated measurements (SDm), and the sensitivity to changes in JSW in serial radiographs (standardized response mean [SRM]).ResultsThe performance of the new software, as assessed by the reproducibility of repeated measurements of minimum JSW on the same image, was excellent in both the standing AP (ICC = 0.98) and Lyon schuss radiographs (2 SDm = 0.5 mm, ICC = 0.98). The reproducibility in different radiographs of the same knee was not evaluated. However, over 2 years, the mean (± SD) decrease in the minimum JSW of OA knees was 0.17 ± 0.75 mm in standing AP radiographs (P not significant) and 0.24 ± 0.50 mm in Lyon schuss views (P = 0.007), with SRMs of 0.23 and 0.48, respectively. The quality of alignment of the tibial plateau was satisfactory (<1 mm between anterior and posterior margins of the medial tibial plateau) in 66% of the pairs of Lyon schuss radiographs and in 57% of the pairs of standing AP radiographs. In the Lyon schuss radiographs, SRM was highly dependent on tibial plateau alignment. Minimum JSW was more sensitive to change than was mean JSW or JSA, in paired Lyon schuss radiographs that exhibited satisfactory alignment.ConclusionCompared with the standing AP radiograph, PA imaging of the knee in 20–30° flexion (the schuss position) increases the reproducibility of radiographic JSW measurements in OA knees and the sensitivity to change in JSW in serial radiographs. Sensitivity to change in minimum JSW is notably increased by aligning the medial tibial plateau with the central x‐ray beam in the Lyon schuss radiograph.
Transcription factor early growth response 1 activity up‐regulates expression of tissue inhibitor of metalloproteinases 1 in human synovial fibroblasts
Authors: Aicher Wilhelm K. , Alexander Dorothea , Haas Christian , Kuchen Stefan , Pagenstecher Axel , Gay Steffen , Peter Hans‐Hartmut , Eibel Hermann 
Published: February 2003

AbstractObjectiveTo investigate the regulatory potential of early growth response 1 (Egr‐1) on tissue inhibitor of metalloproteinases 1 (TIMP‐1) expression in synovial fibroblasts.MethodsEgr‐1 and TIMP‐1 transcripts were detected by in situ hybridization in synovial tissue. Egr‐1–regulated TIMP expression was studied in immortalized fibroblast lines using gel retardation assays, RNase protection analysis, reporter gene studies using the human TIMP‐1 promoter, and by enzyme‐linked immunosorbent assay.ResultsTIMP‐1 and Egr‐1 were coexpressed in synovial fibroblasts of inflamed joints, and Egr‐1 activated the expression of TIMP‐1. Egr‐1 binding to a recognition sequence in the TIMP‐1 promoter was demonstrated in gel retardation and reporter gene assays. Since the same DNA sequence was also recognized by the transcription factor Sp‐1, our results suggest that the expression of TIMP‐1 in synovial fibroblasts may be differentially regulated by Egr‐1 and Sp‐1. In addition, fibroblasts expressing Egr‐1 at high levels were found to express increased levels of TIMP‐2 and TIMP‐3 messenger RNA.ConclusionThe enhanced expression of Egr‐1 may regulate the activity of matrix metalloproteinases in synovial fibroblasts by enhancing the expression of the TIMP‐1, ‐2, and ‐3 genes.
Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement
Authors: Steen Virginia , Medsger Thomas A. 
Published: February 2003

AbstractObjectiveTo determine whether there are factors, such as the diffusing capacity for carbon monoxide (DLCO) or pulmonary artery pressure (PAP) on echocardiogram, that can predict the development of pulmonary hypertension (PHT) in patients with limited scleroderma.MethodsUsing the large Pittsburgh Scleroderma Databank, 106 patients who had the diagnosis of PHT after January 1, 1982, were matched with 106 controls by scleroderma subtype, age, sex, race, disease duration, and the mean time to the diagnosis of PHT after the initial Pittsburgh visit. Autoantibodies, vascular features, use of calcium channel blockers, extent of pulmonary function, and echocardiogram findings were determined at any time prior to the diagnosis of PHT (or prior to the matched time in controls).ResultsPatients with PHT had a mean DLCO of 52% of predicted at an average of 4.5 years prior to the diagnosis of PHT. This was markedly decreased compared with the values in controls, whose mean DLCO was 81% of predicted (P < 0.0001). The estimated mean PAP on echocardiogram was only slightly higher in the PHT patients compared with controls (34 mm Hg versus 29 mm Hg; P not significant). Nineteen PHT patients had 4 serial measurements of the DLCO during the 15 years prior to the diagnosis of PHT. The initial mean DLCO was 80% of predicted, which decreased in a linear manner to a mean of 35% of predicted at the time of diagnosis of PHT, whereas the value in controls remained at ∼80% of predicted (P < 0.0001). PHT patients had more severe Raynaud's phenomenon and more severe digital tip ulcers, but they used calcium channel blockers significantly less frequently (37% versus 61% of controls; P < 0.01). The predominance of nucleolar autoantibodies and the absence of anti–Scl 70 antibody were associated with PHT.ConclusionA decreasing DLCO is an excellent predictor of the subsequent development of isolated PHT in limited scleroderma. The DLCO may be significantly decreased for many years prior to the diagnosis of PHT. The presence of autoantibodies and the PAP may also be helpful predictors. The long‐term use of calcium channel blockers may be protective, but newer agents that are more effective in treating PHT may also be helpful in altering the natural history of this serious complication in limited scleroderma.
Cytokine profile of the rheumatoid nodule suggests that it is a Th1 granuloma
Authors: Hessian Paul A. , Highton John , Kean Annabel , Sun Cheuk Kwan , Chin Michael 
Published: February 2003

AbstractObjectiveTo define the cytokine profile within rheumatoid subcutaneous nodules, and to determine whether the destructive inflammatory process in this lesion displays features of a lymphocyte‐driven Th1 or Th2 granuloma.MethodsSubcutaneous nodules excised from 10 patients with rheumatoid arthritis were examined. Transcripts for interleukin 1β (IL‐1β) IL‐2, IL‐4, IL‐5, IL‐10, IL‐12, IL‐13, IL‐15, IL‐18, and for tumor necrosis factor α (TNFα) and interferon‐γ (IFNγ) were detected by reverse transcription–polymerase chain reaction of extracted RNA.ResultsNine of 10 nodules contained transcripts for IFNγ. We observed no evidence for the expression of IL‐2, IL‐4, or IL‐5 among the lymphokine genes analyzed. Transcripts for TNFα, IL‐1β, IL‐10, IL‐15, and IL‐18 were present in all 10 nodules. Transcripts for IL‐12 were present in all but one nodule. Expression of IL‐13 messenger RNA was observed in only 5 nodules.ConclusionThe cytokine profile within the rheumatoid nodule (i.e., presence of IFNγ but not IL‐2, and prominent expression of IL‐1β and TNFα together with IL‐12, IL‐18, IL‐15, and IL‐10) is similar to the profile of cytokines in the synovial lesion of rheumatoid arthritis, which is generally accepted as being attributable to a Th1‐mediated inflammatory mechanism. Our results suggest that damage to affected synovial membrane or subcutaneous tissue is caused by the same inflammatory mechanisms, and that the nodule is a Th1 granuloma.
Safety and efficacy of long‐term intraarticular steroid injections in osteoarthritis of the knee: A randomized, double‐blind, placebo‐controlled trial
Authors: Raynauld Jean‐Pierre , Buckland‐Wright Chris , Ward Rupert , Choquette Denis , Haraoui Boulos , Martel‐Pelletier Johanne , Uthman Imad , Khy Visithan , Tremblay Jean‐Luc , Bertrand Carole , Pelletier Jean‐Pierre 
Published: February 2003

AbstractObjectiveTo evaluate the safety and efficacy of long‐term intraarticular (IA) steroid injections for knee pain related to osteoarthritis (OA).MethodsIn a randomized, double‐blind trial, 68 patients with OA of the knee received IA injections of triamcinolone acetonide 40 mg (34 patients) or saline (34 patients) into the study knee every 3 months for up to 2 years. The primary outcome variable was radiologic progression of joint space narrowing of the injected knee after 2 years. Measurements of minimum joint space width were performed by an automated computerized method on standardized fluoroscopically guided radiographs taken with the patient standing and with the knee in a semiflexed position. The clinical efficacy measure of primary interest was the pain subscale from the Western Ontario and McMaster Universities OA Index (WOMAC). Efficacy measures of secondary interest were the total score on the WOMAC, physician's global assessment, patient's global assessment, patient's assessment of pain, range of motion (ROM) of the affected knee, and 50‐foot walking time. Clinical symptoms were assessed just before each injection.ResultsAt the 1‐year and 2‐year followup evaluations, no difference was noted between the two treatment groups with respect to loss of joint space over time. The steroid‐injected knees showed a trend toward greater symptom improvement, especially at 1 year, for the WOMAC pain subscale, night pain, and ROM values (P = 0.05) compared with the saline‐injected knees. Using area under the curve analyses, knee pain and stiffness were significantly improved throughout the 2‐year study by repeated injections of triamcinolone acetonide, but not saline (P < 0.05).ConclusionOur findings support the long‐term safety of IA steroid injections for patients with symptomatic knee OA. No deleterious effects of the long‐term administration of IA steroids on the anatomical structure of the knee were noted. Moreover, long‐term treatment of knee OA with repeated steroid injections appears to be clinically effective for the relief of symptoms of the disease.
Geldanamycin inhibits the production of inflammatory cytokines in activated macrophages by reducing the stability and translation of cytokine transcripts
Authors: Wax Stephen , Piecyk Monica , Maritim Beatrice , Anderson Paul 
Published: February 2003

AbstractObjectiveHeat‐shock protein 90 (Hsp90) is critical in the intracellular signaling pathways that promote inflammatory cytokine production. Geldanamycin (GD) is a benzoquinone ansamycin that inhibits the function of Hsp90. GD inhibits the production of tumor necrosis factor α (TNFα) in activated macrophages and suppresses the progression of adjuvant‐induced arthritis and experimental allergic encephalomyelitis in rodents. GD has been used to investigate the mechanisms by which Hsp90 regulates inflammatory cytokine production.MethodsThe macrophage cell line RAW264.7 (or primary peritoneal macrophages) was activated with lipopolysaccharide in the absence or presence of GD. The effect of GD on the transcription, stability, and translation of inflammatory cytokine messenger RNA (mRNA) was determined using nuclear run‐on assays, mRNA decay assays, and sucrose gradient polysome profiles, respectively.ResultsOur data revealed that GD potently inhibits the production of TNFα, interleukin‐6 (IL‐6), and IL‐1β in activated macrophages. Although GD did not significantly reduce the transcription of inflammatory cytokine mRNA, it significantly decreased the stability of these transcripts. Polysome profiles indicated that GD also inhibited the translation of TNFα and IL‐6 transcripts. These effects may be due, in part, to inhibition of p38 mitogen‐activated protein kinase, a kinase known to regulate the stability and translation of inflammatory cytokine transcripts.ConclusionThese results indicate that the function of Hsp90 is important in the posttranscriptional control of inflammatory cytokine production.
Mapping and functional characterization of rat chromosome 4 regions that regulate arthritis models and phenotypes in congenic strains
Authors: Bäckdahl Liselotte , Ribbhammar Ulrica , Lorentzen Johnny C. 
Published: February 2003

AbstractObjectiveDA rats are highly susceptible to experimental models of rheumatoid arthritis (RA). Linkage analyses in different models have identified several quantitative trait loci (QTLs) within a 70‐cM region of DA rat chromosome 4 (C4). We produced congenic strains for these QTLs in order to map and characterize their impact on arthritis development.MethodsSelective breeding was used to transfer C4 intervals from arthritis‐resistant PVG.1AV1 rats onto DA rats. These congenic strains were evaluated for susceptibility to arthritis induced by intradermal injection of rat type II collagen, pristane (a well‐defined synthetic adjuvant oil), mycobacteria, or squalene (an endogenous adjuvant oil used in human vaccine).ResultsRats congenic for PVG.1AV1 genes in the 70‐cM region were less susceptible than DA rats to collagen‐induced arthritis (CIA), pristane‐induced arthritis, adjuvant‐induced arthritis, and squalene‐induced arthritis (SIA). Experiments in subcongenic strains indicated a gene regulating arthritis in males located in a 20‐cM interval overlapping the QTL Pia5. A second gene, located in a 10‐cM interval harboring the QTL Oia2, attenuated SIA and CIA. The latter caused a change in anticollagen antibody isotype levels toward a pattern similar to that seen in PVG.1AV1 rats.ConclusionThe QTL Oia2 regulates arthritis induced both by the nonimmunogenic immunostimulant squalene and by cartilage collagen. In CIA, it also skews anticollagen isotype profiles, suggesting qualitative regulation of autoimmunity. Interestingly, the homologous human chromosome region 12p12–p13 has also been linked to RA, suggesting that genetic and functional dissection of this locus will provide clues to disease pathways that lead to joint inflammation.