bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth factor responsiveness of human articular chondrocytes in aging and development
Authors: Guerne Pierre‐andré , Blanco Francisco , Kaelin André , Desgeorges Alain , Lotz Martin 
Published: February 2007

AbstractObjective. To examine growth factor responses of human articular chondrocytes in aging and development. We have previously established a growth factor response profile for adult human articular chondrocytes and shown that transforming growth factor β (TGFβ) is the most potent mitogen among a variety of factors tested.Methods. Chondrocytes were isolated from human articular cartilage obtained from donors ages 11–83 years and tested in primary culture for proliferative responses to serum and recombinant preparations of the major chondrocyte growth factors. Proliferation was measured by 3H‐thymidine incorporation and cell counting. Skeletal maturity of the young donors was determined by radiographic assessment of Risser's index.Results. Chondrocytes showed a continuous age‐related decline in the proliferative response to serum. Analysis of recombinant growth factors showed that with increasing donor age, there was a decrease in the levels of DNA synthesis in response to all factors tested. In chondrocytes from adult donors, there was no change in the relative potencies of the different growth factors. The decrease in the levels of DNA synthesis as measured by 3H‐thymidine incorporation corresponded to a reduced rate of in vitro cell replication with increasing donor age. In addition to the quantitative changes in the proliferative responses of chondrocytes with increasing age, there was a qualitative change in the pattern of growth factor responses during development. Cells from young donors (ages 10–20) responded better to platelet‐derived growth factor, AA chain homodimer (PDGF‐AA) than to TGFβ1, while the inverse pattern was seen in cells from adult donors. This decrease in the response to PDGF‐AA was significantly correlated with increasing skeletal maturity.Conclusion. Chondrocyte growth factor responsiveness shows qualitative changes during development, and after skeletal maturity, there is a profound decline in the levels of DNA synthesis and cell replication in response to the known chondrocyte growth factors.
Increased levels of stromelysin‐1 and tissue inhibitor of metalloproteinases–1 in sera from patients with rheumatoid arthritis
Authors: Yoshihara Yasuo , Obata Ken'ichi , Fujimot Noboru , Yamashita Kyoko , Hayakawa Taro , Shimmei Masayuki 
Published: February 2007

AbstractObjective. To evaluate the efficacy of stromelysin‐1 (matrix metalloproteinase–3 [MMP‐3]) and tissue inhibitor of metalloproteinases–1 (TIMP‐1) in serum as markers for joint inflammation in rheumatoid arthritis (RA).Methods. Levels of both macromolecules in sera from 97 healthy controls, 109 patients with RA, and 47 patients with osteoarthritis (OA) were measured by respective 1‐step sandwich enzyme immunoassays. In the patients with RA, serum levels of MMP‐3 and TIMP‐1 were investigated in relation to laboratory and clinical measures of disease activity. In addition, the relationships between serum and synovial fluid (SF) levels in paired samples from individual patients were examined.Results. Serum levels of both MMP‐3 and TIMP‐1 in RA patients were significantly higher than those in OA patients and in healthy controls (P < 0.001), and were shown to correlate with traditional systemic markers of inflammation including the erythrocyte sedimentation rate and C‐reactive protein level, and with the Lansbury articular index. In addition, it was noted that serum levels of MMP‐3 correlated with the corresponding values in paired SF samples obtained concurrently from patients with RA (rs = 0.588, P < 0.001), while such correlations were not found for TIMP‐1 levels.Conclusion. Our results support the notion that levels of both MMP‐3 and TIMP‐1 in RA patient sera are increased in association with inflammation. Furthermore, the level of MMP‐3 in serum provides a particularly useful marker of inflammatory activity in the joints of patients with RA.
Comparative analysis of cathepsin l, cathepsin d, and collagenase messenger rna expression in synovial tissues of patients with rheumatoid arthritis and osteoarthritis, by in situ hybridization
Authors: Keyszer Gernot M. , Heer Andreas H. , Kriegsmann JÖRg , Geiler Thomas , Trabandt Andreas , Keysser Martin , Gay Renate E. , Gay Steffen 
Published: February 2007

AbstractObjective. To compare the expression of cathepsin L, cathepsin D, and collagenase messenger RNA (mRNA) in synovial specimens from patients with rheumatoid arthritis (RA) and osteoarthritis (OA).Methods. The expression of cathepsins L and D as well as collagenase mRNA in synovial tissues from 8 patients with RA, 6 patients with OA, and 2 patients with noninflamed joints was evaluated using in situ hybridization with digoxigenin‐labeled RNA probes.Results. Both RA and OA synovial tissue expressed cathepsins L and D as well as collagenase mRNA. The expression of the cathepsins was markedly higher in interstitial regions and, to some extent, in perivascular infiltrates of RA synovial tissue compared with OA specimens.Conclusion. Cathepsins L and D mRNA are expressed differently in RA and OA synovial tissues, supporting the concept that these enzymes may contribute to the influx of mononuclear cells into RA synovium. Moreover, the data reveal that the expression of collagenase and cathepsins in RA and OA synovial lining is otherwise largely similar, and suggest that the adhesion of synovial cells to cartilage mediates the invasive destructive process in RA.
Amplification of plasmid and chromosome chlamydia dna in synovial fluid of patients with reactive arthritis and undifferentiated seronegative oligoarthropathies
Authors: Bas Sylvette , Griffais Rémy , Kvien Tore K. , Glennås Anne , Melby Kjetil , Vischer Thomas L. 
Published: February 2007

AbstractObjective. To investigate the hypothesis that whole bacteria might be found in the joints of patients with Chlamydia‐associated reactive arthritis.Methods. The presence of 2 plasmid‐ and 2 chromosome‐specific sequences of Chlamydia DNA was investigated by amplification with the polymerase chain reaction, in synovial fluid (SF) samples from 71 patients with various arthropathies.Results. Chlamydia DNA was found in SF samples from 22 patients.Conclusion. Whole chlamydiae are likely present in the SF of patients with Chlamydia‐associated reactive arthritis.
The antiinflammatory effects of an adenosine kinase inhibitor are mediated by adenosine
Authors: Cronstein Bruce N. , Naime Dwight , Firestein Gary 
Published: February 2007

AbstractObjective. The acute antiinflammatory effects of methotrexate are mediated, at least in part, by increased extracellular adenosine concentrations at inflamed sites. This observation suggests that other agents that increase extracellular adenosine concentrations might also reduce inflammation. Since adenosine can be rapidly taken up by cells, phosphorylated by adenosine kinase, and maintained intracellularly as adenine nucleotides, we investigated whether a potent inhibitor of adenosine kinase, GP‐1–515, could increase exudate adenosine concentration and thereby diminish inflammation in the murine air pouch model of inflammation.Methods. We studied the effect of various oral doses of GP‐1–515 on carrageenan‐induced inflammation in air pouches induced on BALB/c mice. Adenosine concentration in pouch exudates was determined by high performance liquid chromatography, and intensity of inflammation was determined by leukocyte counts in the exudate fluid.Results.There was a greater concentration of adenosine in the pouch exudates of animals treated with GP‐1–515 than of those treated with saline (P < 0.002). GP‐1‐515 inhibited, in a dose‐dependent manner (P < 0.01), leukocyte accumulation in the murine air pouch in response to carrageenan. Inhibition of inflammation by GP‐1‐515 in this model depended upon increased adenosine concentration in the inflamed pouch since injection of adenosine deaminase into the air pouch with the carrageenan completely reversed the antiinflammatory effects of GP‐1‐515 at all doses of GP‐1‐515 tested. Moreover, as previously demonstrated, the antiinflammatory effects of adenosine were mediated via occupancy of adenosine A2 receptors, since the specific adenosine A2 receptor antagonist 3,7‐dimethyl‐1‐propargylxanthine, but not the A1 receptor antagonist 8‐cyclopentyl‐dipropylxanthine, completely reversed the antiinflammatory effects of GP‐1–515. GP‐1–515 also decreased tumor necrosis factor α levels in the air pouch exudates by 51%, most likely as a result of the direct action of adenosine on macrophages.Conclusion. These results indicate that the antiinflammatory actions of GP‐1–515 are mediated by adenosine. The development of agents that promote adenosine release at sites of inflammation is a novel strategy for the treatment of inflammatory diseases such as rheumatoid arthritis.
Biased t cell receptor vβ gene usage during specific stages of the development of autoimmune sialadenitis in the mrl/lpr mouse model of Sjögren's syndrome
Authors: Hayashi Yoshio , Hamano Hironori , Haneji Norio , Ishimaru Naozumi , Yanagi Kumiko 
Published: February 2007

AbstractObjective. To analyze the repertoire of T cell receptor (TCR) Vβ genes transcribed and expressed within the autoimmune lesions of the salivary gland in the MRL/lpr mouse model of Sjögren's syndrome.Methods. Monoclonal antibodies (MAb) were used to determine the prevalence of selected V gene elements on T cell infiltrates from salivary glands of MRL/lpr mice. To analyze TCR Vβ gene usage, we used reverse‐transcriptase polymerase chain reaction (RT‐PCR) and single‐strand conformational polymorphism (SSCP) analyses.Results. A predominance of Vβ 8+ T cells was detected within the inflammatory lesions during development of autoimmune disease (confirmed by flow cytometry). RT‐PCR analysis revealed that in autoimmune sialadenitis, the predominant expression of the Vβ 8 gene segment began in the early stages of disease (2‐month‐old mice) and increased over time. Extensive age‐related diversity of TCR Vβ gene usage was also observed. SSCP analysis demonstrated a distinct and common binding pattern of the Vβ 8 gene PCR product from the cell infiltrates during the course of the disease.Conclusion. Our data suggest that in the MRL/lpr mouse model of Sjögren's syndrome, there is restricted usage of TCR Vβ elements according to the stage of the disease, and that Vβ 8 are probably used preferentially in the recognition of a single unknown self antigen in the salivary gland.
Even low‐grade synovitis significantly accelerates the clearance of protein from the canine knee: implications for measurement of synovial fluid “markers” of osteoarthritis
Authors: Myers Stephen L. , Brandt Kenneth D. , Eilam Oron 
Published: February 2007

AbstractObjective. In recent studies, the synovial fluid concentration of molecules derived from the extracellular matrix of articular cartilage has been used to deduce the magnitude of cartilage destruction or repair in osteoarthritic (OA) joints. Because low‐grade synovitis is often present in such joints, we assessed the effect of synovial inflammation on the clearance of a prototypical protein, albumin, from synovial fluid.Methods. 131‐labeled albumin (RISA) was injected into 1 (control) knee of each of 14 dogs. The concentration of RISA in synovial fluid aspirated 7 hours after the injection and serial measurements of surface radioactivity were used to calculate the volume of distribution (Vd) and clearance of RISA. One week later, synovitis was induced in the contralateral knee by intraarticular injection of various quantities of calcium pyrophosphate dihydrate (CPPD) crystals, after which RISA was injected into that joint and these measurements were repeated.Results. Intraarticular injection of 500 μg of CPPD crystals produced intense synovitis, with a mean synovial fluid white blood cell (WBC) count of 43,200 cells/mm3, and values for RISA Vd and RISA clearance (36.5 ml and 33.7 μl/minute) were much higher than those for saline‐injected control knees (2.7 ml and 1.5 μl/minute, respectively). Injection of 0.5 μg of CPPD also produced marked synovitis and values for Vd and RISA clearance that were 2–3‐fold greater than those in the contralateral knee. The low‐grade synovitis produced by only 0.05 μg of CPPD, which resulted in synovial fluid WBC counts as low as 1,000–2,000 cells/mm3, was accompanied by increases in the clearance and Vd of RISA to levels ˜40% and ˜80% higher, respectively, than those for the contralateral knee.Conclusion. Even mild synovitis, as seen in OA, may significantly increase the clearance of a protein from the joint. Synovitis is a significant variable which must be considered in studies of putative chondroprotective drugs if conclusions about the effects of drugs on cartilage metabolism are to be drawn from changes in the synovial fluid concentration of a “marker” protein.
Suppression of antigen‐induced arthritis in lewis rats by oral administration of type ii collagen
Authors: Yoshino Shin , Quattrocchi Emilia , Weiner Howard L. 
Published: February 2007

AbstractObjective. To assess the effect of orally administered type II collagen (CII) in antigen‐induced arthritis (AIA).Methods. Arthritis was induced in Lewis rats by immunization with methylated bovine serum albumin (mBSA) in Freund's complete adjuvant, followed by an intraarticular injection of mBSA 2 weeks later. Different doses of CII, mBSA, and an unrelated control protein, keyhole limpet hemocyanin (KLH), were orally administered 5 times over several days prior to the induction of arthritis. Ankle joint swelling and delayed‐type hypersensitivity (DTH) responses were measured.Results. Joint swelling was significantly reduced at a dose of 3 μg and 30 μg of CII, but not at 300 μg. The most prominent suppression of AIA was observed when rats were fed 10 mg of mBSA, whereas oral KLH had no effect. DTH responses were significantly reduced in the mBSA‐fed rats, but not in rats that were fed CII or KLH.Conclusion. Oral CII can suppress arthritis in an animal model in which immunity to collagen does not play a role. The effect is dose dependent and occurs at lower doses of CII. These results demonstrate the biologic relevance of bystander suppression associated with oral tolerance, and the potential use of this approach to treat human inflammatory joint disease.
Effects of high‐dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs clinical and immune correlates
Authors: Kremer Joel M. , Lawrence David A. , Petrillo Gayle F. , Litts Laura L. , Mullaly Patrick M. , Rynes Richard I. , Stocker Ralph P. , Parhami Nourollah , Greenstein Neal S. , Fuchs Betsy R. , Mathur Anupum , Robinson Dwight R. , Sperling Richard I. , Bigaouette Jean 
Published: February 2007

AbstractObjective. To determine the following: 1) whether dietary supplementation with fish oil will allow the discontinuation of nonsteroidal antiinflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA); 2) the clinical efficacy of high‐dose dietary ω3 fatty acid fish oil supplementation in RA patients; and 3) the effect of fish oil supplements on the production of multiple cytokines in this population.Methods. Sixty‐six RA patients entered a double‐blind, placebo‐controlled, prospective study of fish oil supplementation while taking diclofenac (75 mg twice a day). Patients took either 130 mg/kg/day of ω3 fatty acids or 9 capsules/day of corn oil. Placebo diclofenac was substituted at week 18 or 22, and fish oil supplements were continued for 8 weeks (to week 26 or 30). Serum levels of interleukin‐1β (IL‐1β), IL‐2, IL‐6, and IL‐8 and tumor necrosis factor α were measured by enzyme‐linked immunosorbent assay at baseline and during the study.Results. In the group taking fish oil, there were significant decreases from baseline in the mean (±SEM) number of tender joints (5.3 ± 0.835; P < 0.0001), duration of morning stiffness (−67.7 ± 23.3 minutes; P = 0.008), physician's and patient's evaluation of global arthritis activity (−0.33 ± 0.13; P = 0.017 and −0.38 ± 0.17; P = 0.036, respectively), and physician's evaluation of pain (−0.38 ± 0.12; P = 0.004). In patients taking corn oil, no clinical parameters improved from baseline. The decrease in the number of tender joints remained significant 8 weeks after discontinuing diclofenac in patients taking fish oil (−7.8 ± 2.6; P = 0.011) and the decrease in the number of tender joints at this time was significant compared with that in patients receiving corn oil (P = 0.043). IL‐1β decreased significantly from baseline through weeks 18 and 22 in patients consuming fish oil (−7.7 ± 3.1; P = 0.026).Conclusion. Patients taking dietary supplements of fish oil exhibit improvements in clinical parameters of disease activity from baseline, including the number of tender joints, and these improvements are associated with significant decreases in levels of IL‐1β from baseline. Some patients who take fish oil are able to discontinue NSAIDs without experiencing a disease flare.
Usefulness of the american college of rheumatology recommendations for liver biopsy in methotrexate‐treated rheumatoid arthritis patients
Authors: Erickson Alan R. , Reddy Vishnu , Vogelgesang Scott A. , West Sterling G. 
Published: February 2007

AbstractObjective. To test the usefulness and cost savings resulting from application of the new American College of Rheumatology (ACR) guidelines for assessing the risk for the development of clinically significant liver disease in rheumatoid arthritis (RA) patients treated with methotrexate (MTX).Methods. One‐hundred twelve MTX‐treated RA patients were prospectively followed up for MTX hepatotoxicity and underwent liver biopsies according to modified guidelines of the Psoriatic Task Force (PTF). All biopsies were graded according to the Roenigk classification. The new ACR recommendations were then retrospectively applied to test their usefulness and cost‐effectiveness in this cohort.Results. Based on the PTF guidelines, 66 patients underwent liver biopsies; a total of 110 liver biopsies were performed. Two patients had biopsy‐related complications. Five patients were found to have Roenigk grade IIIB or IV histologic abnormalities. The total cost for this group was $111,380. Applying the new ACR criteria, only 15 patients would have undergone liver biopsies; there would have been a total of 18 biopsies, with no complications. Four of the 5 patients with Roenigk grade IIIB or IV liver abnormalities would have been identified. One patient with insulin‐dependent diabetes mellitus (IDDM) who was found to have cirrhosis (Roenigk grade IV) on liver biopsy as a result of use of the PTF guidelines would have been missed with use of the ACR guidelines. The total cost for the group receiving biopsies based on the ACR guidelines would have been $16,956. Overall, the new ACR guidelines had 80% sensitivity and 82% specificity and resulted in a cost savings of $1,430 per patient.Conclusion. The new ACR guidelines on MTX monitoring and biopsy surveillance appear to be clinically useful and result in considerable cost savings. However, 1 IDDM patient with significant liver histologic abnormalities would have been missed. We suggest that IDDM be added to the ACR guidelines as a risk factor for MTX hepatotoxicity.
Access to medical care among persons with musculoskeletal conditions
Authors: Yelin Edward , Bernhard Gerson , Pflugrad Diane 
Published: February 2007

AbstractObjective. To study access to medical care services, including subspecialty care, among persons with musculoskeletal conditions.Methods. In early 1993, a random sample of households in San Mateo County, California, was screened for the presence of household members with musculoskeletal conditions, and a member of each household so identified was administered a structured survey about access to medical care and other related subjects.Results. Eighty‐six percent of all persons with a musculoskeletal condition had ever seen at least one physician for the condition, but only 6.5% had ever seen a rheumatologist. Those without health insurance were only 82% as likely as those with health insurance to have ever seen a physician.Conclusion. Most persons with a musculoskeletal condition have seen a physician for the condition, but lack of health insurance significantly reduces the proportion who have done so.
Incidence of symptomatic hand, hip, and knee osteoarthritis among patients in a health maintenance organization
Authors: Oliveria Susan A. , Felson David T. , Reed John I. , Cirillo Priscilla A. , Walker Alexander M. 
Published: February 2007

AbstractObjective. To quantify the incidence of symptomatic hand, hip, and knee osteoarthritis (OA) among members of the Fallon Community Health Plan, a health maintenance organization located in central Massachusetts.Methods. Incident OA was defined as the first evidence of OA by radiography (grade ≥2 on the Kellgren‐Lawrence scale of 0–4) plus joint symptoms at the time the radiograph was obtained or up to 1 year before the radiograph was obtained.Results. The age‐ and sex‐standardized incidence rate for hand OA was 100/100,000 person‐years (95% confidence interval [95% CI] 86, 115), for hip OA 88/100,000 person‐years (95% CI 75, 101), and for knee OA 240/100,000 person‐years (95% CI 218, 262). The incidence of hand, hip, and knee OA increased with age, and women had higher rates than men, especially after age 50. A leveling off or decline occurred for both groups around the age of 80.Conclusion. In a large study of symptomatic OA we observed incidence rates that increased with age. In women ages 70‐89, the incidence of knee OA approached 1% per year.and women had higher rates than men, especially after age 50. A leveling off or decline occurred for both groups around the age of 80.
Photoexacerbation of cutaneous lupus erythematosus due to ultraviolet a emissions from a photocopier
Authors: Klein Laura R. , Elmets Craig A. , Callen Jeffrey P. 
Published: February 2007

AbstractThis report describes a woman with systemic lupus erythematosus (LE) who worked as a photocopy technician and developed cutaneous LE of the hands, neck, face, and chest. Her skin lesions improved when she discontinued her employment. Testing of several photocopy devices showed emission of small quantities of ultraviolet A (UVA), but no UVB. Phototesting of the patient with UVA and UVB induced skin lesions that were clinically and histopathologically consistent with LE. Thus, the action spectrum of cutaneous LE may be within the UVB range, the UVA range, or both ranges of the solar spectrum, and repeated exposure to short bursts of light may induce clinical disease. This case suggests that occupational sources of UV light should be considered as possible exacerbating factors in LE.