bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional studies of soluble low‐affinity interleukin‐2 receptors in rheumatoid synovial fluid
Authors: Miossec Pierre , Elhamiani Majida , Edmonds‐Alt Xavier , Sany Jacques , Hirn Michel 
Published: February 2007

AbstractSince abnormal regulation of interleukin‐2 (IL‐2) has been demonstrated in rheumatoid arthritis (RA), the functional role of low‐affinity soluble IL‐2 receptors (sIL‐2R) purified from RA synovial fluids (SF) was studied. Picomolar levels of sIL‐2R were detected in RA SF using an enzyme‐linked immunosorbent assay. Levels were higher in serum and SF from RA patients than in controls (P < 0.001) and higher in RA SF than in paired RA serum (P < 0.01). Soluble IL‐2R from RA SF had estimated molecular weights of 40‐50 kd and 80–100 kd by gel filtration analysis. The 80–100‐kd peak is likely to be a dimer of the 40–50‐kd peak, since a single 45‐kd peak was found after elution from sodium dodecyl sulfate‐polyacrylamide gels. Since inhibitory activity for lymphocyte proliferation was found in the 80–100‐kd range, the sIL‐2R were purified with an anti‐CD25 affinity column and further analyzed. The purified fractions did not interfere with the proliferation of mitogen‐stimulated lymphocytes or with the binding of radiolabeled IL‐2 to CTLL‐2 cells, although direct binding of IL‐2 was demonstrated. The affinity of sIL‐2R from RA SF for binding IL‐2 was in the range of 25 nM, which is similar to the affinity of sIL‐2R purified from a human T cell clone, indicating that both sIL‐2R are low‐affinity receptors for IL‐2. We conclude that the concentration and binding affinity of low‐affinity sIL‐2R purified from RA SF render them unable to interfere with IL‐2‐related activities.
Inhibition of interleukin‐1‐induced collagenase production in human articular chondrocytes in vitro by recombinant human interferon‐gamma
Authors: Andrews H. J. , Bunning R. A. D. , Plumpton T. A. , Clark I. M. , Russell R. G. G. , Cawston T. E. 
Published: February 2007

AbstractThe production of collagenase by human articular chondrocytes in response to interleukin‐1β is inhibited in a dose‐dependent manner by interferon‐γ (1–1,000 units/ml). The analysis of culture medium samples by Western blotting and the measurement of levels of tissue inhibitor of metalloproteinases suggest that the decrease in measurable collagenase activity is primarily due to the inhibition of procollagenase production. These results provide evidence of a role for interferon‐γ in limiting connective tissue degradation.
Yersinia Enterocolitica In the synovial membrane of patients with Yersinia‐induced Arthritis
Authors: Hammer Michael , Zeidler Henning , Klimsa Silvia , Heesemann JÜRgen 
Published: February 2007

AbstractUsing a monospecific rabbit antibody against Yersinia enterocolitica outer membrane protein 1, we examined synovial biopsy specimens from 7 patients with Yersinia‐induced arthritis. Yersinia were demonstrated in the synovial membrane by indirect immunofluorescence in 4 patients with Yersinia‐induced arthritis, but not in 6 control patients with Salmonella‐induced arthritis or with rheumatoid arthritis. These findings suggest the persistence of Yersinia in the joints of patients with Yersinia‐induced arthritis.
Catabolic effects of muramyl dipeptide on rabbit chondrocytes
Authors: Ikebe Tetsuro , Iribe Hideaki , Hirata Masato , Yanaga Fumi , Koga Toshitaka 
Published: February 2007

AbstractMuramyl dipeptide, an essential structure for the diverse biologic activities of bacterial cell wall peptidoglycan, inhibited the synthesis of glycosaminoglycan/proteoglycan in cultured rabbit costal chondrocytes in a dose‐dependent manner. Muramyl dipeptide, as well as lipopolysaccharide and interleukin‐1α, also enhanced the release of 35S‐sulfate—prelabeled glycosaminoglycan/proteoglycan from the cell layer, which seems to reflect, at least partially, the increasing degradation of glycosaminoglycan/proteoglycan. Five synthetic analogs of muramyl dipeptide known to be adjuvant active or adjuvant inactive were tested for their potential to inhibit synthesis of glycosaminoglycan/proteoglycan and to enhance the release of glycosaminoglycan/proteoglycan in chondrocytes. The structural dependence of these synthetic analogs on chondrocytes was found to parallel that of immunoadjuvant activity. These results suggest that muramyl dipeptide is a potent mediator of catabolism in chondrocytes.
Inhibition of 5‐lipoxygenase product formation and polymorphonuclear cell degranulation by tenidap sodium in patients with rheumatoid arthritis
Authors: Blackburn Warren D. , Heck Louis W. , Loose Leland D. , Eskra J. D. , Carty T. J. 
Published: February 2007

AbstractWe studied the effect of tenidap sodium, a new antiinflammatory/antirheumatic drug (120 mg/day for 7 days), on eicosanoid production and neutrophil degranulation in patients with rheumatoid arthritis. Endogenous prostaglandin E2 levels and ex vivo production of leukotriene B4 (LTB4) were measured in synovial fluid samples obtained at baseline and 1 week later. We measured peripheral blood polymorphonuclear cell (PMN) degranulation following surface‐bound IgG stimulation, a possible 5‐lipoxygenase product–mediated event, by determining lactoferrin and elastase release into the culture fluid. We found decreased levels of endogenous prostaglandin E2 as measured by radioimmunoassay, and decreased ex vivo production of LTB4 by PMN as measured by high performance liquid chromatography, in synovial fluid samples from patients who took tenidap. Release of the granule proteins lactoferrin and elastase was decreased in PMN obtained from patients receiving tenidap, as well as in the PMN incubated in vitro with tenidap. Improvement in clinical measures paralleled the biochemical changes. The unique 5‐lipoxygenase inhibitory property of tenidap, as measured by LTB4 production and degranulation, suggests that it may have clinical activity which differentiates it from nonsteroidal antiinflammatory drugs.
Tenidap, in contrast to several available nonsteroidal antiinflammatory drugs, potently inhibits the release of activated neutrophil collagenase
Authors: Blackburn Warren D. , Heck Louis W. , Loose Leland D. , Chatham W. Winn 
Published: February 2007

AbstractNeutrophils contain a collagenase that is stored in a latent form within the specific granule. With cellular activation, the latent enzyme is activated in association with the production of a variety of oxidants, including hypochlorous acid. We evaluated 4 nonsteroidal antiinflammatory drugs (NSAIDs) currently on the market and the new antiinflammatory/antirheumatic drug tenidap for their effects on the release of activated collagenase. In contrast to the 4 NSAIDs, tenidap profoundly inhibited the release of activated collagenase. This inhibition was predominantly due to interference with activation of the latent enzyme, rather than interference with enzyme release. The inhibition of collagenase activation was associated with a profound reduction in myeloperoxidase activity and in hypochlorous acid production. These observations demonstrate that tenidap has properties that set it apart from conventional NSAIDs and suggest that it may be a particularly useful agent in the treatment of inflammatory rheumatic disorders.
In vivo leukocyte migration in arthritis
Authors: Jones Anthony K. P. , Al‐Janabi Mazim A. , Solanki Kishor , Sobnack Ravin , Greenwood Allison , Doyle David V. , Britton Keith E. , Huskisson Edward C. 
Published: February 2007

AbstractWe quantitated in vivo migration of neutrophils into the knees of patients with rheumatoid arthritis (RA) and osteoarthritis, using 99mtechnetium–hexamethyl‐propylene‐amineoxime–labeled leukocytes and gamma scintigraphy. Significant neutrophil migration occurred in patients with RA irrespective of disease duration, and it was reduced by 60% following intraarticular steroid injection. The reduction in neutrophil migration correlated with reduction in pain. Leukocyte migration into osteoarthritic joints was also demonstrated, although it was much less than that seen in rheumatoid joints. No significant leukocyte migration into the joints of patients without arthritis was demonstrated. This technique appears to provide a sensitive method for quantitatively assessing the neutrophil component of inflammation in individual joints of patients with arthritis.
Amelioration of lapine osteoarthritis by treatment with glycosaminoglycan–peptide association complex (Rumalon)
Authors: Dean David D. , Muniz Ofelia E. , Rodriquez Ivette , Carreno Manuel R. , Morales Sara , Agundez Agueda , Madan Maria Elena , Altman Roy D. , Annefeld Marliese , Howell David S. 
Published: February 2007

AbstractThe chondroprotective potential of glycosaminoglycan–peptide association complex (GP‐C) was examined in the medial meniscectomy model of lapine osteoarthritis (OA). Prophylactic treatment with increasing doses of intramuscular GP‐C (0.05–0.5 ml/kg) caused a significant reduction in OA lesion area and histologic scores, and the effect on disease activity appeared to be dose related. The DNA and uronic acid contents of OA tissue were unaffected by prophylactic treatment with GP‐C. However, levels of hydroxyproline in OA cartilage increased to near control levels with prophylactic treatment. Cartilage levels of active and total metalloproteinases that digest proteoglycans were elevated in rabbits with OA; prophylactic treatment with low‐dose GP‐C (0.05 ml/kg) produced a significant reduction in active, but not total, enzyme. Cartilage levels of tissue inhibitor of metalloproteinases in animals with OA were comparable with control levels, but rose with increasing doses of GP‐C. We also investigated GP‐C as a therapeutic treatment in animals that had already developed OA lesions. Carbon black retention and histologic score returned to near‐normal after therapeutic treatment with GP‐C. Uronic acid and hydroxyproline levels were decreased in OA cartilage. Therapeutic treatment with GP‐C had no statistically significant effect on uronic acid levels, but was associated with increased hydroxyproline content in the cartilage. The changes in metalloproteinase and metalloproteinase inhibitor were similar to those found in the studies of prophylactic treatment. The findings in this animal model may help explain some of the beneficial effects of GP‐C in human OA.
Restricted diversity of the variable region nucleotide sequences of the heavy and light chains of a human rheumatoid factor
Authors: Ezaki Ichiko , Shingu Masao , Nobunaga Masashi , Kanda Hidetoshi , Watanabe Takeshi , Sakai Kouko , Fukui Nobunori 
Published: February 2007

AbstractThe complete nucleotide sequences of the variable region genes of the heavy and light polypeptide chains of a human monoclonal rheumatoid factor (RF) produced from a human–mouse heterohybridoma were determined. The antibody, designated YES8c, contained V κIII, Jκ2, VH1, JH4, and a D gene segment of 9 amino acids. The nucleotide sequences and the deduced amino acid sequences of the light chain variable region were remarkably homologous (97–98%) to previously described RF of the Wa idiotypic family (PAY, GLO, CUR, FLO, and GAR) and to that of a VκIII germline gene (Humkv325). The YES8c heavy chain variable region gene was most closely related to the VH1 gene of the restricted human fetal repertoire, designated 51p1, and also to 3 rearranged VH1 genes that were recently isolated from patients with chronic lymphocytic leukemia. These results suggest that variable region genes of RFs are highly conserved and that YES8c VH, as well as Vκ, may be identical to heavy and light chains expressed during early B cell development.
A double‐blind randomized controlled trial of ketotifen versus placebo in early diffuse scleroderma
Authors: Gruber Barry L. , Kaufman Lee D. 
Published: February 2007

AbstractTo determine the efficacy of the mast cell‐stabilizing drug ketotifen in scleroderma, we conducted a 6‐month, randomized, prospective, double‐blind, placebo‐controlled trial in 24 patients. No significant improvement in the clinical paramenters, pulmonary function, global assessments, and mast cell releasability was noted. Pruritus tended to improve in the group taking the active drug. Six months of treatment with ketotifen (6 mg/day), therefore, produced no apparent benefit in patients with early scleroderma. We were unable to address the role of mast cells in scleroderma since mast cell suppression was not achieved.
Relationship between arthroscopic evidence of cartilage damage and radiographic evidence of joint space narrowing in early osteoarthritis of the knee
Authors: Fife Rose S. , Brandt Kenneth D. , Braunstein Ethan M. , Katz Barry P. , Shelbourne K. Donald , Kalasinski Lorrie A. , Ryan Sarah 
Published: February 2007

AbstractWe examined the relationship between articular cartilage degeneration, as visualized arthroscopically, and joint space narrowing (JSN) in standing anteroposterior knee radiographs of 161 patients with chronic knee pain. The majority of these patients had radiographic findings of mild osteoarthritis. Twenty‐five (33%) of the 76 patients in the series whose radiographs showed tibiofemoral JSN had grossly normal articular cartilage in both tibiofemoral compartments at arthroscopy (false‐positive). The specificity of medial JSN for the presence of medial compartment articular cartilage degeneration was 0.61, i.e., only 61% of patients with normal (grade 0) medial compartment cartilage had a normal medial joint space. Of 22 patients with >50% medial JSN, 9 (41%) had normal articular cartilage in the medial compartment at arthroscopy. Of 6 patients with >50% lateral JSN, 3 (50%) had normal lateral compartment articular cartilage at arthroscopy. Among 36 patients with >25% JSN who had neither medial nor lateral compartemnt articular cartilage degeneration, JSN was associated with articular caartilage degeneration, JSN was associated with articular cartilage degeneration in the patellofemoral compartemnt in 8 (22%), with meniseus degeneration in 18 (50%), and with both in 8 (22%). Thus, in these patients with chronic knee pain, radiographic evidence of JSN in the tibiofemoral compartment did not permit confident prediction of the status of the articular cartilage.
T cell proliferation induced by Borrelia burgdorferi in patients with lyme borreliosis. Autologous serum required for optimum stimulation
Authors: Krause Andreas , Kalden Joachim R. , Burmester Gerd R. , Brade Volker , Schoerner Christoph , Solbach Werner 
Published: February 2007

AbstractThe cellular immune response to Borrelia burgdorferi was studied in 24 patients with seropositive and seronegative Lyme borreliosis, 30 patients with arthritides of different origin (non‐Lyme arthritides), and 20 normal blood donors. By far, the strongest T cell stimulation was induced by incubation with autologous serum; there was a significantly lower response or no response after incubation with allogeneic or heterologous sera. In patients with Lyme borreliosis, including seronegative patients, there was a strikingly elevated proliferation in response to whole B burgdorferi bacteria (mean 64,750 dpm) compared with that of normal donors (mean 19,700 dpm; P < 0.0001) and especially that of non‐Lyme arthritis patients (mean 11,600 dpm; P <0.0001). Levels of proliferation declined significantly in patients with Lyme borreliosis after successful antibiotic treatment. Parallel cultures using B burgdorferi and Treponema phagedenis as antigens showed that cells from patients with Lyme borreliosis responded significantly more to B burgdorferi than to T phagedenis, but this did not occur with cells from individuals with non‐Lyme arthritides. There was no correlation between disease stages and proliferation values. These data indicate that lymphocyte proliferation assays may provide an important tool for the diagnosis of Lyme borreliosis, most notably in patients with arthritides and in those who are seronegative. Conversely, the lack of reactivity appears to be a strong indicator of the absence of active Lyme disease. It seems to be crucial, howeveer, to use autologous sera in these assays.
The effects of cyclosporin a on eicosanoid excretion in patients with rheumatoid arthritis
Authors: Weinblatt M. , Helfgott S. , Coblyn J. , Spragg J. , Tumeh S. , Sperling R. , Maier A. , Uedelhoven W. M. , Lorenz R. , Weber P. 
Published: February 2007

AbstractAlterations in renal eicosanoid levels have been postulated as a factor in cyclosporin A (CSA) nephro‐toxicity. The effects of CSA on renal eicosanoid excretion in rheumatoid arthritis were studied over a 24‐week period, during which treatment with nonsteroidal anti‐inflammatory drugs was discontinued. The initial dosage of CSA was 4 mg/kg/day; at week 24, the mean dosage of CSA was 3.9 mg/kg/day. At week 24, the mean (±SD) serum creatinine level (1.04 ± 0.24 mg/dl) was 32% above the baseline value; renal blood flow had decreased by 21% (P < 0.03) and the glomerular filtration rate had decreased by 16%. There was a significant increase (P < 0.03) in the 2,3‐dinor thromboxane B2 level at week 2, but there was no significant change in the levels of the other eicosanoids. This study demonstrates that after CSA treatment, there is a selective increase in a thromboxane metabolite that parallels an increase in renal vascular resistance, even in the absence of nonsteroidal antiinflammatory drugs, and with unimpaired formation of other vasodilator eicosanoids.
Morphologic and morphometric changes in synovial membrane associated with mechanically induced osteoarthrosis
Authors: Boyd R. D. , Walker E. R. , Wu D. D. , Lukoschek M. , Burr D. B. , Radin E. L. 
Published: February 2007

AbstractWe sought to determine whether synovial leukocytic inflammation is a primary event in mechanically induced osteoarthrosis. Repetitive impulse loading (50 ms duration at 60 Hz for 40 minutes each day) was applied to the right hindlimbs of 24 New Zealand white rabbits for 3, 6, or 9 weeks. The synovial membrane from the medial suprapatellar area was examined qualitatively using transmission electron microscopy and quantitatively using light microscopic morphometry. The results indicate that synovial inflammation is not a primary event in this mechanically induced osteoarthrosis, but synovial hyperplasia occurs prior to histologically evident cartilage destruction at 6–9 weeks.
Evidence for autoimmunity in the tight skin mouse model of systemic sclerosis
Authors: Bocchieri Maureen H. , Henriksen Paul D. , Jimenez Sergio A. , Kasturi Kuppuswamy N. , Muryoi Tai , Bona Constantin A. 
Published: February 2007

AbstractThe tight skin mouse strain has been proposed for use as an animal model of systemic sclerosis because this animal exhibits a condition that has biochemical and pathologic similarities to the human disease. To date, however, evidence of inflammatory and immunologic changes in the tight skin mouse has been scarce. We demonstrated the presence of antinuclear antibodies in approximately half of these mice ages 8 months and older. This suggests that there is an autoimmune component in their disease process. The antibodies were identified as anti–topoisomerase I by a characteristic staining pattern on HEp‐2 cells and by Western blot analysis. Except for a low incidence of anti‐DNA antibodies, none of the other parameters tested, including mitogen responses, lymphokine production, and anti‐erythrocyte antibodies, was indicative of immune system dysregulation.
T lymphocyte–synovial fibroblast interactions induced by mycobacterial proteins in rheumatoid arthritis
Authors: Holoshitz Joseph , Kosek Jon , Sibley Richard , Brown Daniel A. , Strober Samuel 
Published: February 2007

AbstractAn in vitro system was established in which single‐cell suspensions of lymphocytes and synovial cells from the joints of patients with rheumatoid arthritis were cultured and produced an outgrowth of an organized inflammatory tissue with an extracellular matrix and capsule. The tissue outgrowth, which had histologic features of pannus, required the addition of mycobacterial antigen and interleukin‐2 to the tissue culture medium and was dependent upon the presence of T lymphocytes and their interaction with synovial fibroblasts.
Autosomal dominant arthropathy in a french family
Authors: Gaucher Alain , Weryha Georges , Perrier Pascale , Moreau Paul , Pere Patrice , Gillet Pierre , Vu Vincent Dang 
Published: February 2007

AbstractWe studied a French family in which 18 adult members had destructive arthropathy and enthesopathic changes. In 16 patients, the diagnosis was verified radiologically, and in the 2 other patients, the clinical history was consistent with familial arthropathy. The disease predominantly affects the wrists, fingers, shoulders, and peripheral entheses, and its onset occurs after age 18. Genetic transmission is autosomal dominant, with 100% penetrance, and is not related to the HLA system. The clinical and radiologic features are strikingly similar in all patients in successive generations and different branches of the genealogic tree, and this suggests monogenic transmission.
Neutrophil chemotactic factors in synovial fluids of patients with lyme disease
Authors: Georgilis Kostis , Noring Richard , Steere Allen C. , Klempner Mark S. 
Published: February 2007

AbstractWe examined synovial fluid samples from 14 patients with Lyme arthritis for the presence of neutrophil chemotactic factors. Thirteen of the synovial fluids stimulated chemotaxis of normal human neutrophils. The chemotactic activity was heat‐sensitive and was not inhibited by antibody to C5a or antibody to interleukin‐8, or by a competitive inhibitor of the chemotactic peptide f‐Met‐Leu‐Phe. A culture supernatant of Borrelia burgdorferi also contained neutrophil chemoattractants. Chromatography demonstrated that the chemoattractants in the synovial fluid samples were different from those in the B burgdorferi culture supernatant. One of the major chemotactic factors in Lyme disease synovial fluid had a calculated molecular weight of 13,900. We conclude that a novel, host‐derived chemoattractant is present in the synovial fluid of patients with Lyme disease.
Expression of large quantities of rheumatoid factor major cross‐reactive idiotype in the serum of adults with seropositive rheumatoid arthritis
Authors: Wedgwood Josiah F. , Hatam Lynda , Bonagura Vincent R. 
Published: February 2007

AbstractWe quantified rheumatoid factor cross‐reactive idiotype (RF‐CRI) in whole serum from RF+ rheumatoid arthritis (RA) patients, using an inhibition enzymelinked immunosorbent assay which is not affected by the presence of IgG. Serum from 16 RF+ RA patients contained 2–252 μg/ml RF‐CRI (geometric mean */÷ SD 20.8 */÷ 5.2), while serum from 11 normal adults contained 1–16 μg/ml RF‐CRI (geometric mean */÷ SD 3.9 */÷ 2.3). Serum from 8 of the RF+ RA patients contained RF‐CRI at concentrations more than 2 standard deviations above the geometric mean in the normal subjects (>21 μg/ml). Our results indicate that some RF+ RA patients express high concentrations of RF‐RCRI and immunoglobulin molecules that express the RF‐CRI may not be RF.