bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of l‐tryptophan and an illness resembling eosinophilic fasciitis: clinical and histopathologic findings in four patients with eosinophilia‐myalgia syndrome
Authors: Bulpitt Ken J. , Verity M. Anthony , Clements Philip J. , Paulus Harold E.
Published: February 2007

The Centers for Disease Control has recently reported an association between the use of oral L‐tryptophan preparations and a disease marked by severe myalgia, peripheral eosinophilia, and neuromuscular and cutaneous abnormalities. They have labeled the condition eosinophilia‐myalgia syndrome. We report here the clinical and histopathologic findings in 4 patients who developed an illness resembling eosinophilic fasciitis following the initiation of oral L‐tryptophan supplementation.
The in vitro effects of methotrexate on peripheral blood mononuclear cells: Modulation by methyl donors and spermidine
Authors: Nesher Gideon , Moore Terry L.
Published: February 2007

The mode of action of low‐dose methotrexate (MTX) in rheumatoid arthritis (RA) is unclear. The effects of MTX are mediated primarily through inhibition of dihydrofolate reductase, resulting in a dose‐dependent inhibition of purine and pyrimidine synthesis. Other folate‐dependent metabolic pathways might be secondarily affected. One such pathway is the regeneration of methionine from homocysteine, with subsequent formation of the methyl donor S‐adenosylmethionine (SAM) and polyamines, which are important in cell‐mediated immune reactions. To assess whether MTX inhibits SAM and polyamine synthesis in lymphocytes, pokeweed mitogen‐stimulated mononuclear cells from healthy donors were incubated with MTX. This resulted in decreased proliferation and IgG, IgM, and IgM rheumatoid factor synthesis. However, addition of folinic acid, methionine, SAM, or spermidine resulted in reversal of the MTX‐mediated inhibition. These data suggest that MTX inhibits the folate‐dependent pathway of methionine regeneration, thereby inhibiting SAM and polyamine synthesis. Since RA lymphocytes have increased concentrations of polyamines, the beneficial effects of MTX in RA may be related to its potential ability to reduce polyamine synthesis.
Antibody to signal recognition particle in polymyositis
Authors: Targoff Ira N. , Johnson Arthur E. , Miller Frederick W.
Published: February 2007

Using immunoprecipitation, we identified 13 patients with antibodies to the signal recognition particle (SRP) from a collection of sera representing 265 poly‐myositis/dermatomyositis (PM/DM) patients. Antibody reactivity with SRP was confirmed by enzyme‐linked immunosorbent assay and immunoprecipitation with isolated dog pancreas SRP. The antibody was present in the serum of 4% of PM/DM patients, and 18% of PM/ DM patients with anticytoplasmic antibodies other than anti‐Jo‐1, but not in patients with other conditions who had anticytoplasmic antibodies. Anti‐SRP was associated with classic adult PM, and some of these cases were unusually severe and/or of rapid onset; it was not found in patients with overlap syndromes or with DM involvement. Unlike patients with antibodies to aminoacyl‐transfer RNA synthetases, patients with anti‐SRP had a low frequency of pulmonary fibrosis, as well as of arthritis and Raynaud's phenomenon. Anti‐SRP antibodies may serve as a marker for a second, distinct subgroup of adult PM.
Cartilage proteoglycan‐induced arthritis in BALB/c mice. Antibodies that recognize human and mouse cartilage proteoglycan and can cause depletion of cartilage proteoglycan with little or no synovitis
Authors: Dayer Eric , Mathai Lalitha , Glant T. T. , Mikecz K. , Poole A. Robin
Published: February 2007

Human fetal cartilage proteoglycan (PG) induces the development of an erosive polyarthritis and spondylitis in BALB/c mice. We have examined the properties of 3 monoclonal antibodies (MAb) to human fetal cartilage PG isolated from immunized mice that cross‐react with mouse cartilage PG. Compared with sera from arthritic mice, which contain antibodies reactive with keratan sulfate, MAb 202 (IgG1) reacted only with a protein‐related epitope that is distributed on both hyaluronic acid‐binding and chondroitin sulfate‐attachment regions. MAb 813 (IgG1) reacted with the same fragments and recognized an epitope with the immunologic characteristics of keratan sulfate. MAb 945 (IgM) remains to be further characterized. Introduction of hybridomas secreting MAb 202 and MAb 945 into irradiated mice resulted in the loss of PG from articular cartilage and from growth plate cartilage (with MAb 202 only), as revealed by a loss of staining with toluidine blue. There was no synovial hyperplasia with MAb 202, but some hyperplasia and mononuclear cell infiltration was seen with MAb 945. This was accompanied by the binding of immunoglobulins to articular cartilage, as demonstrated by immunofluorescence. The hybridoma secreting MAb 813 produced no cartilage changes or synovitis, and there was no immunoglobulin binding to cartilage. Polymorphonuclear leukocyte infiltration was never observed with these antibodies. These studies indicate that MAb reactive with mouse cartilage PG can cause the depletion of PG from hyaline cartilage by mechanisms that may be both complement dependent and complement independent. Antibodies may serve to release and expose PG antigen to immune cells, as well as causing a loss of the mechanical properties of cartilage that are PG dependent.
Binding of anti‐DNA antibodies and inhibition of glomerulonephritis in MRL‐lpr/lpr mice by heparin
Authors: Naparstek Yaakov , Ben‐Yehuda Arie , Madaio Michael P. , Bar‐Tana Ruth , Schuger Lucy , Pizov Galina , Neeman Zvi , Cohen Irun R.
Published: February 2007

Heparin was found to inhibit the DNA binding of antibodies eluted from kidneys of both humans and MRL‐lpr/lpr mice with systemic lupus erythematosus. Treatment of MRL‐lpr/lpr mice with low doses of heparin significantly inhibited renal damage. These results suggest that low‐dose heparin might be useful in preventing renal damage in patients with lupus nephritis.
Human immunodeficiency virus‐associated psoriasis, psoriatic arthritis, and Reiter's syndrome: A disease continuum?
Authors: Reveille John D. , Conant Marcus A. , Duvic Madeleine
Published: February 2007

The presence of peripheral arthritis and HLA‐A, B, C, DR, and DQ antigens was evaluated prospectively in 18 Caucasian men with human immunodeficiency virus‐associated psoriasis. An asymmetric polyarthritis occurred in 32% of the patients and correlated with the presence of HLA‐B27. Extensive clinical overlap between psoriatic arthritis, psoriasis, and Reiter's syndrome was noted. No significant excess of the HLA antigens previously found to be associated with psoriasis was seen, which suggests that human immunodeficiency virus‐associated psoriasis per se may instead constitute another form of spondylarthropathy that is more closely related to Reiter's syndrome.
Intravenous pulse cyclophosphamide therapy in myositis and Sjögren's syndrome
Authors: Leroy J. P. , Drosos A. A. , Yiannopoulos D. I. , Youinou P. , Moutsopoulos H. M.
Published: February 2007

We describe a patient with primary Sjögren's syndrome who developed myositis. The results of muscle pathologic analysis before and after treatment with monthly pulses of cyclophosphamide (intravenously), are presented.
Interleukin‐1‐induced interleukin‐6 is required for the inhibition of proteoglycan synthesis by interleukin‐1 in human articular cartilage
Authors: Nietfeld J. J. , Wilbrink B. , Helle M. , Roy J. L. A. M. Van , Otter W. Den , Swaak A. J. G. , Huber‐Bruning O.
Published: February 2007

Cartilage from normal controls, patients with osteoarthritis, and patients with rheumatoid arthritis produced no interleukin‐6 (IL‐6) in culture. However, IL‐1 induced massive production of IL‐6 (up to 135 ng/ml) in cartilage from all 3 sources, in a dose‐dependent manner (in some cases, a peak value was reached). The levels of induced IL‐6 were similar to those found in rheumatoid arthritis synovial fluid. At IL‐1 concentrations that induced almost complete inhibition of proteoglycan (PG) synthesis, IL‐6 production could still be increased considerably. Exogenous IL‐6 inhibited PG synthesis by up to 25%. IL‐1‐induced inhibition of PG synthesis was reversed by antibodies against recombinant human IL‐6. These results suggest that IL‐6 is required for the IL‐1‐induced inhibition of PG synthesis.
Pregnancy and the risk of developing rheumatoid arthritis
Authors: Hazes J. M. W. , Dijkmans B. A. C. , Vandenbroucke J. P. , Vries R. R. P. De , Cats A.
Published: February 2007

There have been conflicting reports on, and no plausible biologic explanation for, a protective effect of oral contraceptive (OC) use on the development of rheumatoid arthritis (RA). Therefore, we investigated aspects of behavior related to OC use that could explain the preventive effect of OC on the onset of RA. In the present case—control study, past pregnancy, age at first pregnancy, and pregnancies with adverse outcome were studied as possible risk factors for RA. Interview information on reproductive variables was obtained from 135 young adult women with confirmed definite or classic RA of recent onset, and from 378 control patients with soft tissue rheumatic disorders or osteoarthritis. All patients had at least 2 years of followup to confirm the consistency of the diagnosis. We found a decreased risk of RA in women who had been pregnant. The risk of RA in women who had ever been pregnant compared with women who had never been pregnant was 0.49 (95% confidence interval 0.27–0.91). The earlier the first pregnancy, the lower the risk of RA. Pregnancy with adverse outcome (i.e., gestation <25 weeks) did not substantially change the risk of RA (relative risk 0.73, 95% confidence interval 0.50–1.07). The protective effect of pregnancy was independent of OC use, the presence of HLA–DR4, or a family history of RA. Immune modulation by female hormonal influences could be an explanation for the results of the present study.
Role of cytokines in inflammatory synovitis
Authors: Chin Jia En , Winterrowd Greg E. , Krzesicki Raymond F. , Sanders Martin E.
Published: February 2007

This study was undertaken in an effort to understand the role of cytokines in T lymphocyte trafficking into inflamed synovium and in the potential enhancement of antigen presentation by human synovial fibroblasts. We found that interleukin‐1β (IL‐1β), tumor necrosis factor α (TNFα), and interferon‐γ (IFNγ) each increased the cell surface expression of intercellular adhesion molecule 1 (ICAM‐1) on human synovial fibroblasts in a dose‐ and time‐dependent manner. Maximal ICAM‐1 expression occurred within 8 hours of induction, with the following order of efficacy: IFNγ > TNFα > IL‐1β. The number of cells bearing the ICAM‐1 antigen also increased, from a basal level of ∼30% to more than 83% after cytokine induction (for all 3 cytokines). ICAM‐1 expression rapidly decreased following cytokine removal. The expression of lymphocyte function‐associated antigen 3 was also examined, but it was not changed by any of the 3 cytokines. Class I major histocompatibility complex antigen expression was increased modestly by all 3 cytokines, and expression was maximal by 24 hours after treatment. Only IFNγ induced HLA class II antigen expression, and this expression persisted for up to 6 days following removal of the lymphokine. IL‐6 and granulocyte‐macrophage colony‐stimulating factor had no effect on any of the parameters examined. Our data support an interactive role for inflammatory cytokines and the expression of adhesion ligands and HLA antigens by human synovial fibroblasts in the pathogenesis of synovial inflammation in rheumatoid arthritis.
Antihistone antibodies in antinuclear antibody—positive juvenile Arthritis
Authors: Monestier Marc , Losman Julie A. , Fasy Thomas M. , Debbas Michael E. , Massa Margherita , Albani Salvatore , Bohm Lothar , Martini Alberto
Published: February 2007

The binding of antinuclear antibody—positive juvenile arthritis (JA) sera to bovine thymus histones H1, H2A, H2B, H3, and H4 was studied by an enzyme‐linked immunosorbent assay. Seventy‐five percent of the JA patients tested positive for at least 1 antibody specificity. Antihistone antibodies were predominantly IgM, while IgG antibodies were less common and were restricted to histones H1 or H3. In the group of patients with JA of pauciarticular onset, antihistone antibodies were significantly more elevated in patients with past or present uveitis than in patients without a history of uveitis. Anti‐H1 antibodies in JA patients were found to react mostly with determinants located in the carboxylterminal domain of the H1 molecule. Sera were also reactive with human histone H1° or chicken histone H5, which are H1 variants found only in nondividing cells.
Adrenal insufficiency in two women with anticardiolipin antibodies
Authors: Levy Ernesto N. , Ramsey‐Goldman Rosalind , Kahl Leslie E.
Published: February 2007

We describe 2 women with anticardiolipin antibodies and a lupus‐like disorder who developed acute adrenal insufficiency. We also review 5 similar cases reported previously. Anticardiolipin antibodies appear to be a risk factor for this vascular complication.
Increased expression of intercellular adhesion molecule 1 on the fibroblasts of scleroderma patients
Authors: Needleman Barbara White
Published: February 2007

The surface expression of intercellular adhesion molecule 1 (ICAM‐1) and class I and class II major histocompatibility complex molecules on cultured dermal fibroblasts from 7 scleroderma patients and 6 control donors was compared. Scleroderma fibroblast lines contained 41.0 ± 3.0% (mean ± SEM) cells with high levels of ICAM‐1 expression (ICAM‐1—high), whereas 26.9 ± 1.5% of control fibroblasts were ICAM‐1—high (P = 0.0003). There were no differences in the expression of class I and class II molecules. ICAM‐1—high and ICAM‐1—low fibroblasts produced equal amounts of total protein and procollagen. The increase in the number of ICAM‐1—high fibroblasts in scleroderma patients may facilitate T cell activation and lymphokine production, and thus indirectly contribute to the fibrotic process.
Double‐blind, placebo‐controlled study of three‐month treatment with lymecycline in reactive arthritis, with special reference to Chlamydia arthritis
Authors: Lauhio Anneli , Leirisalo‐Repo Marjatta , Lähdevirta Juhani , Saikku Pekka , Repo Heikki
Published: February 2007

We conducted a double‐blind, placebo‐controlled, randomized study of 3‐month treatment with lymecycline, a form of tetracycline, in reactive arthritis (ReA). Lymecycline therapy significantly decreased the duration of the illness in patients with Chlamydia trachomatis‐triggered ReA, but not in other ReA patients. In 2 ReA patients, C trachomatis was found in the throat, an uncommon locale for this organism. Our results suggest that it is important to verify the triggering microbe and that it is beneficial to treat Chlamydia arthritis patients with a prolonged course of tetracycline.
Chondrons from articular cartilage. III. Morphologic changes in the cellular microenvironment of chondrons isolated from osteoarthritic cartilage
Authors: Poole C. Anthony , Matsuoka Akira , Schofield Jennifer R.
Published: February 2007

Chondrons were isolated from human and canine osteoarthritic cartilage using low‐speed homogenization techniques. Changes in chondron morphology were evaluated using differential interference–contrast microscopy, phase‐contrast microscopy, and histochemical and ultrastructural methods. Chondrocyte viability was assessed using fluorescein diacetate staining, and chondron metabolism was investigated using autoradiography. The results suggest that initial changes in the collagen and proteoglycan distribution within the chondron are followed by chondrocyte proliferation to form clusters. These techniques offer the potential to study cell matrix interactions in degenerative osteoarthritis.
Induction of arthritis in rats by aqueous suspensions of mycobacteria without the use of oil
Authors: Levine Seymour , Saltzman Arthur
Published: February 2007

We report for the first time the induction of arthritis by an aqueous, rather than an oil, suspension of killed tubercle bacilli. This was accomplished in the highly susceptible dark Agouti strain of rats, by intraperitoneal injection during the healing phase of chemically induced peritonitis. The same procedure (injection after the induction of peritonitis) augmented the incidence of arthritis produced by bovine type II collagen and Freund's complete adjuvant. Enhanced delivery of antigen from the peritoneal cavity to regional lymph nodes in the postinflammatory state was responsible for this increase in the induction of arthritis.
Complete heart block and severe aortic incompetence in relapsing polychondritis: Clinicopathologic findings
Authors: Bowness Paul , Hawley Ian C. , Morris Tom , Dearden Andrew , Walport Mark J.
Published: February 2007

We describe a patient with relapsing polychondritis who developed fatal cardiac involvement comprising complete heart block, acute aortic incompetence, and cardiovascular collapse. Pathologic studies showed fibrosis of the cardiac conducting system and necrotizing inflammation of the aortic valve, features not previously described in relapsing polychondritis, as well as evidence of coronary artery vasculitis.
HLA–D region antigens in patients with rheumatoid arthritis
Authors: McCusker Christine T. , Reid Barbara , Green Donna , Gladman Dafna D. , Buchanan W. Watson , Singal Dharam P.
Published: February 2007

We studied the distribution of HLA–D region antigens in 2 groups of rheumatoid arthritis (RA) patients: those with mild, nonprogressive disease, and those with severe disease. The results demonstrate that DR4 was significantly increased in both RA patient populations. The frequencies of DR1 and DR4‐associated DQw7 alleles, howevever, were different in these 2 groups of patients. DR1 was significantly increased only in patients with mild RA, and DR4‐associated DQw7 was significantly increased only in patients with severe disease. The results of the present study, together with previous data from our laboratory and from other investigators on the incidence of HLA–D region antigens in RA, suggest that both DR and DQ (A and B) genes may be important in conferring susceptibility to RA; DR in the mild forms of the disease, and DQ in severe RA.
Rheumatic symptoms and human immunodeficiency virus infection. The influence of clinical and laboratory variables in a longitudinal cohort study
Authors: Calabrese Leonard H. , Kelley Dennis M. , Myers Andrew , O'Connell Michelle , Easley Kirk
Published: February 2007

The present study was designed to prospectively evaluate the frequency of rheumatic symptoms in a cohort of patients infected with the human immunodeficiency virus (HIV), to examine the relationship between such findings and a variety of clinical and epidemiologic variables, and to evaluate the impact of rheumatic symptoms on the natural history of the HIV infection. One hundred seventeen patients were evaluated over a mean of 24.6 months (range 0.5–85 months). Cumulatively, 1.7% had Reiter's syndrome, 1.7% had psoriatic arthritis, and 11.1% had various forms of oligoarticular/monarticular or polyarticular arthritis. The majority of the rheumatic symptoms developed during the longitudinal evaluation and predominantly affected patients with clinically advanced HIV infection. Patients with articular disease tended to have more progressive HIV infection and were more likely to experience disease progression to clinical acquired immunodeficiency syndrome or death. Our data suggest that the occurrence of rheumatic symptoms in the presence of HIV infection is not uncommon and tends to develop over time, in the setting of clinically advanced retroviral infection. Furthermore, the presence of rheumatic symptoms may be a sign of a poor prognosis for patients with HIV infection.
Interactions between interleukin‐1 and basic fibroblast growth factor on articular chondrocytes. Effects on cell growth, prostanoid production, and receptor modulation
Authors: Chin Jia En , Hatfield Cheryl A. , Krzesicki Raymond F. , Herblin William F.
Published: February 2007

The interactions of interleukin‐1β (IL‐1β) and basic fibroblast growth factor (bFGF) with monolayer cultures of rabbit articular chondrocytes were examined. Both agonists resulted in a synergistic increase in prostanoid production, to levels higher than the maximal level for either protein alone. The synergy was time‐and dose‐dependent, was augmented in serum‐free medium, and was blocked by indomethacin or a polyclonal antibody to IL‐1β. The proteins had opposite effects on cell growth, and IL‐1β completely blocked the mitogenic effect of bFGF. Pretreatment of cells with IL‐1β induced a down‐regulation in the number of the bFGF high‐affinity receptors. Pretreatment of cells with bFGF increased the number of IL‐1 receptors, which was dependent on messenger RNA synthesis.
Severe fibromyalgia after hypophysectomy for cushing's disease
Authors: Disdier Patrick , Harle Jean‐Robert , Chambourlier Pierre , Weiller Pierre‐Jean , Brue Thierry , Jaquet Philippe , Grisoli François
Published: February 2007

We report a case of fibromyalgia occurring after hypophysectomy for Cushing's disease. Clinical examination revealed tender points at 12 of the 18 tender point sites described in the American College of Rheumatology 1990 criteria for the classification of fibromyalgia. The cause of fibromyalgia remains unknown. In our patient, hypophysectomy may have played a role by disturbing endorphin secretion and pain modulation.
Nonsteroidal antiinflammatory drug therapy in rheumatoid arthritis patients. Lack of association between clinical improvement and effects on sleep
Authors: Lavie P. , Nahir M. , Lorber M. , Scharf Y.
Published: February 2007

Thirteen patients with rheumatoid arthritis (mean ± SD age 55.8 ± 10.5 years) received 20 mg of tenoxicam daily for 90 days following a 3–7‐day “washout” period and 4 days of placebo treatment. Clinical evaluations were conducted at the end of the washout period and at monthly intervals thereafter. All‐night polysomnography was performed in a sleep laboratory during the last 2 days of placebo treatment and on days 13, 14, 89, and 90 of tenoxicam treatment. Although there was improvement in the patients' clinical condition, there were no treatment‐related changes in any of the sleep parameters. Eight of the 13 patients, however, were found to have primary sleep disorders. Four had periodic leg movements during sleep, 3 had sleep apneas, and 1 had a combination of both disorders. The implications of these findings in the treatment of sleep disorders in patients with rheumatoid arthritis are discussed.
The impact of rheumatoid arthritis on the household work performance of women
Authors: Allaire Saralynn H. , Meenan Robert F. , Anderson Jennifer J.
Published: February 2007

We conducted a study to assess whether and to what degree household work disability exists in women with rheumatoid arthritis (RA) and to examine the role of health versus family and personal factors as predictors of household work disability. In addition, the participation of other family members and paid employees in household work was evaluated. One hundred forty‐two women with RA and 58 female friends/neighbors completed questionnaires which assessed household work performance and health, family, and personal variables. Performance was measured in 4 ways: the current amount of time spent on household work, the proportion of the household work done, and the changes in time and proportion since just before the onset of RA. Functional status was measured via the Health Assessment Questionnaire. Pain, anxiety and depression, and general health perception were measured via the Arthritis Impact Measurement Scales. The results indicate that household work disability exists in women with RA, but is substantial only in women with moderate‐to‐severe disease. In families in which the wife/mother has moderate‐to‐severe RA, the other family members spend 7 hours more per week on household work than in control families, but there was no increase in the use of paid household employees. Health factors were the strongest predictors of household work disability, but family and personal factors also had significant effects. Household work disability in women with moderate or severe RA merits more attention because of the importance of household work to family functioning and the negative effects that changes in this area can produce.
Identification and characterization of opsonic fibronectin in synovial fluids of patients with active rheumatoid arthritis
Authors: Kay Jonathan , Austen K. Frank , Czop Joyce K.
Published: February 2007

A cofactor that selectively opsonizes particulate activators of the human alternative complement pathway and enhances their phagocytosis by human monocytes was identified in synovial fluids of patients with rheumatoid arthritis. The active material was present in fluids treated with protease inhibitors, was heat stable, and was unaffected by incubation with hyaluronidase. Chromatographic isolation of synovial fluid fibronectin by gelatin affinity and by immunoaffinity on antifibronectin monoclonal antibody BD4 yielded similar quantities of protein for each of 3 fluids. Synovial fluid proteins with the BD4 fibronectin epitope accounted for essentially all of the phagocytosis‐enhancing activity and expressed this activity by opsonizing target activators. Additional chromatographic analyses of synovial fluid fibronectin with the BD4 epitope were carried out using Sepharose‐bearing gelatin and 4 additional antifibronectin monoclonal antibodies. The opsonic materials were characterized as having 2 distinct fibronectin epitopes, which always mapped from the cell adhesive domain to the carboxyl‐terminus of plasma fibronectin, but only rarely contained the gelatin binding domain.
SWR mice are resistant to collagen‐induced arthritis but produce potentially arthritogenic antibodies
Authors: Reife Robert A. , Loutis Nikolous , Watson William C. , Hasty Karen A. , Stuart John M.
Published: February 2007

SWR mice are resistant to collagen‐induced arthritis but produce antibodies to type II collagen. To determine if these antibodies have arthritogenic potential, serum from collagen‐immunized mice was concentrated and passively transferred to DBA/1 mice. The recipients developed severe arthritis within 72 hours. To evaluate the role of complement, SWR mice were bred with congenic inbred B10.D2/oSn (complement deficient) and B10.D2/nSn (complement normal) mice. Collagen‐immunized (SWR × B10.D2/nSn)F1 mice had high levels of C5 and were susceptible to arthritis, while (SWR × B10.D2/oSn)F1 mice were deficient in C5 and were resistant to arthritis.
Elevated plasma levels of hyaluronate in patients with osteoarthritis and rheumatoid arthritis
Authors: Goldberg Ronald L. , Huff John P. , Lenz Mary Ellen , Glickman Paul , Katz Robert , Thonar EUgene J.‐M. A.
Published: February 2007

Plasma levels of hyaluronate (HA) in patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA), measured by enzyme‐linked immunosorbent assay, were compared with levels in a healthy, age‐matched non‐arthritic control group, in a retrospective study. Compared with the controls, the mean level of plasma HA was sevenfold higher in the RA group and twofold higher in the OA group. There was no statistically significant correlation between HA levels and 7 other clinical and biochemical parameters in patients with RA. In the OA group, however, plasma HA levels were found to correlate with an objective functional capacity score and with an articular index based on the total amount of cartilage in involved joints. In a retrospective longitudinal study of 6 patients with RA, plasma levels of HA did not show a significant correlation with plasma levels of elastase or with the erythrocyte sedimentation rate. These data support in part the contention that plasma HA may be unique as a marker, in that it may be a reflection of synovial involvement and inflammation, rather than only of inflammation, in arthritis.
Selective expansion of t cells bearing the γ/δ receptor and expressing an unusual repertoire in the synovial membrane of patients with rheumatoid arthritis
Authors: Andreu Jose L. , Trujillo Angeles , Alonso Jose M. , Mulero Juan , Martínez‐A Carlos
Published: February 2007

In a study of 7 patients with rheumatoid arthritis (RA), we characterized the T cell population present in the synovial membrane, thought to be the location where T cells trigger the disease. Synovial membrane lymphocytes from the RA patients were found to have a selective expansion of γ/δ T cells (8.8% in synovial membrane versus 4% in peripheral blood). Expansion of the γ/δ T cell subset was not found in the synovial membrane of patients with osteoarthritis. We characterized the γ/δ T cell repertoire using monoclonal antibodies TiγA, BB3, and δTCS1, which recognize the gene products encoded by Vγ9, Vδ2, and Vδ1‐Jδ1, respectively. The majority of the synovial γ/δ T cells did not express the repertoire encoded by these genes, which is found in nearly 100% of the peripheral blood γ/δ T cells of healthy volunteer donors and in the thymus at early stages of development. We conclude that the synovial membrane of patients with RA displays a selective expansion of a specific population of γ/δ T cells expressing a clonotypic receptor not yet serologically defined, which might be implicated in the development of the disease.
Subclass distribution and size of human IgA rheumatoid factor at mucosal and nonmucosal sites
Authors: Otten Henny G. , Daha Mohamed R. , Van Laar Jacob M. , De Rooy Hennie H. , Breedveld Ferdinand C.
Published: February 2007

Elevated serum levels of IgA, IgA1, and IgA2 rheumatoid factors (RF) were demonstrated by enzymelinked immunosorbent assay in 69%, 73%, and 36%, respectively, of 100 patients with rheumatoid arthritis (RA), whereas fewer than 5% of 100 healthy donor sera contained elevated levels of these RFs. In serum samples from 125 controls with 4 different chronic diseases (systemic lupus erythematosus, ankylosing spondylitis, bronchial asthma, and polyarteritis nodosa), levels of IgA‐, IgA1‐, and IgA2‐RF were found to be increased in 7%, 7%, and 8%, respectively. Comparison of RF levels in samples of serum, synovial fluid (SF), and saliva from RA patients indicated local production of both IgA‐RF subclasses in salivary glands and in synovial tissue. Significant positive correlations were found between levels of IgA‐RF subclasses in SF and serum, but not in serum and saliva or in SF and saliva. Fractionation of serum, SF, and saliva from patients with RA (by high performance liquid chromatography under acidic conditions) demonstrated that both IgA subclasses with RF activity occur mainly in fractions that also contain IgM. The results of this study show that 1) IgA‐RF in serum and SF is mainly of IgA1 subclass, 2) both IgA‐RF subclasses are produced locally in salivary glands and in synovial tissue, 3) the production of both IgA‐RF subclasses at mucosal and nonmucosal sites is independent from each other, and 4) both IgA‐RF subclasses occur predominantly in polymeric form in serum, SF, and saliva in RA patients.
Endothelin, an endothelial‐dependent vasoconstrictor in scleroderma. Enhanced production and profibrotic action
Authors: Kahaleh M. Bashar
Published: February 2007

The vascular endothelium is an important functional unit in the regulation of the vascular and perivascular environment. Various chemical and physical stimuli mediate an endothelial‐dependent vasoconstriction through the release of endothelial soluble factors, such as the recently recognized endothelium‐derived vasoconstrictor peptide called endothelin. The presence of circulating endothelin and the effect of cold exposure on plasma endothelin levels were investigated in patients with scleroderma and in healthy control subjects. Radioimmunoassay demonstrated a mean ± SD plasma level of 10.7 ± 7.3 pg/ml in the patients (n = 19) and 3.7 ± 2 in the control subjects (n = 16) (P < 0.005). These levels were also assessed in 5 control subjects and 5 scleroderma patients before and after 30 minutes of total body cooling (to 15°C). The endothelin level did not change significantly in either group; however, 2 scleroderma patients showed a significant increase after cooling. The effects of endothelin on fibroblast proliferation and collagen synthesis were evaluated in order to assess the impact of released endothelin on the interstitium. A significant mitogenic effect and a collagen synthesis–enhancing effect, which were dose‐dependent, were seen. The strong, characteristically prolonged, vasoconstrictor activity coupled with the profibrotic effect demonstrated here make it likely that disturbances in the control of endothelin production can contribute to the pathogenesis of scleroderma.
Treatment of refractory chronic Lyme arthritis with arthroscopic synovectomy
Authors: Schoen Robert T. , Aversa John M. , Rahn Daniel W. , Steere Allen C.
Published: February 2007

Of 20 patients who underwent arthroscopic synovectomy for refractory chronic Lyme arthritis of the knee, 16 (80%) had resolution of joint inflammation during the first month after surgery or soon thereafter, and they have remained well during the 3–8‐year followup period. Three of these 16 patients who were more disabled preoperatively, still had mild functional limitation at long‐term followup. The remaining 4 patients (20%) had persistent or recurrent synovitis. We conclude that arthroscopic synovectomy is effective in treating chronic Lyme arthritis in patients in whom the disease does not respond to antibiotic therapy.
Familial Erythema Nodosum
Authors: Elkayam Ori , Caspi Dan , Segal Rafael , Brautbar Chaim , Ben‐Chetrit Eldad , Yaron Michael
Published: February 2007

Erythema nodosum (EN) is a hypersensitivity reaction associated with many diseases. We describe a family in which 4 sisters had acute or recurrent EN. HLA typing showed a common haplotype in the affected members of the family. A review of familial EN and HLA distribution in EN is presented.
Strategies for Reducing Excess Morbidity and Mortality in Blacks With Systemic Lupus Erythematosus
Authors: Liang Matthew H. , Partridge Alison J. , Daltroy Lawren H. , Straaton Karin V. , Galper Sharon R. , Holman Halsted R.
Published: February 2007

The epidemiology of systemic lupus erythematosus suggests that the excess morbidity and mortality in blacks with the disease is related to lower socioeconomic status. Poverty and factors associated with poverty are powerful predictors of poor outcome in a variety of chronic diseases, and lupus appears to be no exception. A body of studies in other illnesses suggests ways to neutralize, at least partially, the disadvantages of lower socioeconomic status, even though the root causes of poverty may be insurmountable. These include improving access to quality health care; targeting educational programs to promote recognition and understanding of the disease and the comorbid conditions that affect outcome; implementing programs to improve self‐monitoring and adherence to medical regimens; developing opportunities to facilitate homemaking, childrearing, and working outside the home; and applying psychosocial interventions to enhance self‐confidence and social support. Improved access to quality health care may actually lead to a decrease in health care costs.
Allopurinol Sensitivity in a Patient With Chronic Tophaceous Gout: Success of Intravenous Desensitization After Failure of Oral Desensitization
Authors: Walz‐Leblanc Barbara A. E. , John Reynolds W. , Macfadden Douglas K.
Published: February 2007

Sensitivity to allopurinol, which occurs in 10–15% of patients, can seriously limit the drug's use in chronic tophaceous gout. Oral allopurinol desensitization has been advocated for sensitive patients in whom use of the drug is warranted. We report the successful use of intravenous allopurinol desensitization in a patient with chronic tophaceous gout in whom oral desensitization had previously failed.
Generation and Characterization of two Monoclonal Self‐Associating IgG Rheumatoid Factors from a Rheumatoid Synovium
Authors: Lu Edward W. , Deftos Michael , Tighe Helen , Carson Dennis A. , Chen Pojen P.
Published: February 2007

Objective. To study IgG rheumatoid factor (RF) from rheumatoid synovium.

Methods. We fused the K6H6/B5 human—mouse heterohybridoma with unstimulated rheumatoid synovial B cells to generate IgG‐RF—secreting hybridomas.

Results. The RFs from 2 such hybridomas bound specifically to the Fc fragment of human IgG and self‐associated to form immune complexes. Such immune complexes are a major characteristic of the pathogenic IgG‐RFs in rheumatoid synovium.

Conclusion. IgG‐RF—secreting hybridomas have been obtained. Analyses may reveal the underlying mechanisms of the induction of IgG‐RF.
Decreased Accessory Cell Function and Costimulatory Activity BY 1, 25‐Dihydroxyvitamin D3—Treated Monocytes
Authors: Rigby WILLIAM F. C. , Waugh Mary G.
Published: February 2007

To characterize the mechanism(s) by which 1,25‐dihydroxyvitamin D3 (calcitriol) modulates the costimulatory capacity of monocytes, we examined the effect of calcitriol pretreatment of monocytes on their capacity to promote T cell proliferation (accessory cell function). Correlation of calcitriol‐dependent changes in monocyte accessory cell function and alterations in phenotype and cytokine production, and the dependence of these changes on cell viability, were studied. Calcitriol pretreatment induced a defect in accessory cell function that was evident with fixed monocytes, suggesting a cell‐surface—associated mechanism. Altered accessory cell function did not correlate with changes in HLA—DR antigen expression and was unaffected by concurrent treatment with interferon‐γ. Calcitriol treatment did not alter either the expression of adhesion molecules or monocytic production of interleukin‐1β (IL‐1β) or IL‐6. Exogenous IL‐1 or IL‐6 did not overcome the impaired costimulatory activity of calcitriol‐treated monocytes. Thus, calcitriol treatment reduces the capacity of monocytes to promote lectin‐induced T cell activation at the level of the plasma membrane, perhaps through altered expression of an uncharacterized molecule important in monocyte—T cell interactions. At chronically inflamed sites, elaboration of calcitriol by activated macrophages may regulate the ability of monocytes to induce both antigen‐dependent and antigen‐independent T cell proliferation.
Anti—Ro/SS‐a Antibodies in the Pathophysiology of Congenital Heart Block in Neonatal Lupus Syndrome, An Experimental Model
Authors: Alexander Elaine , Buyon Jill P. , Provost Thomas T. , Guarnieri Thomas
Published: February 2007

Objective. To determine whether anti—Ro/SS‐A antibodies selectively bind to neonatal cardiac cells and alter membrane repolarization.

Methods. An in vitro electrophysiologic and immunocytochemical experimental model contrasting neonatal and rabbit cardiac tissue was employed.

Results. Sera and IgG‐enriched fractions from anti—Ro/SS‐A antibody—positive mothers of infants with neonatal lupus erythematosus and congenital heart block bind to neonatal, rather than adult, rabbit cardiac tissue and alter the transmembrane action potential (i.e., inhibit repolarization). The additional presence of anti—La/SS‐B antibodies was not additive or synergistic for these immunocytochemical and electrophysiologic features. Sera containing other antibody specificities (i.e., anti—native DNA, cardiolipin, Sm, and nuclear RNP) failed to stain the neonatal cardiac tissue or produce alterations in membrane repolarization.

Conclusion. Anti—Ro/SS‐A antibodies may play a pathophysiologic role in the development of congenital heart block in neonatal lupus.
Low levels of somatomedin C in patients with the fibromyalgia syndrome. A possible link between sleep and muscle pain
Authors: Bennett Robert M. , Clark Sharon R. , Campbell Stephen M. , Burckhardt Carol S.
Published: February 2007

Objective. Fibromyalgia is a common syndrome of musculoskeletal pain and fatigue. Lacking distinctive tissue or laboratory correlations, it has often been considered a form of “psychogenic rheumatism.” In the present study, the notion that the stage‐4 sleep anomaly typically seen in the fibromyalgia syndrome may disrupt growth hormone secretion was tested. Because growth hormone has a very short half‐life, serum levels of somatomedin C were measured; somatomedin C is the major mediator of growth hormone's anabolic actions and is a prerequisite for normal muscle homeostasis.

Methods. Serum levels of somatomedin C were measured in 70 female fibromyalgia patients and 55 healthy controls, using a peptide‐specific radioimmunoassay.

Results. Significantly lower levels of somatomedin C were observed in the fibromyalgia patients compared with controls (mean ± SD 124.7 ± 47 ng/ml versus 175.2 ± 60 ng/ml; P = 0.000001). These results could not be explained by concomitant therapy or by weight, and in a subset of 21 patients in whom this was investigated, there was no correlation with various indices of disease activity.

Conclusion. These findings indicate that there is a distinctive disruption of the growth hormone‐somatomedin C neuroendocrine axis in a majority of fibromyalgia patients. It is hypothesized that this abnormality may explain the link between disturbed sleep and predisposition to muscle pain.
High‐dose immunoglobulin therapy as an immunomodulatory treatment of rheumatoid arthritis
Authors: Tumiati Bruno , Casoli Patrizia , Veneziani Maura , Rinaldi Gabriele
Published: February 2007

Objective. To investigate the efficacy of high‐dose intravenous immunoglobulin (IVIg) in the treatment of refractory rheumatoid arthritis (RA).

Methods. Ten patients with active, severe RA that was unresponsive to first‐ and second‐line agents were administered IVIg monthly, for 6 months.

Results. Following IVIg treatment, there was significant improvement in both subjective and objective parameters of disease activity in all 9 patients who completed the protocol. This improvement was noted to occur as early as after the second infusion of IVIg. After discontinuation of the treatment, all patients had a relapse of the disease within a few weeks.

Conclusion. Since the reduction in clinical activity paralleled a decrease in the CD4+CDw29+: CD4+CD45RA+ cell ratio, some of the therapeutic benefits associated with IVIg may be due to a direct influence on the CD4+CD45RA+ subset. Although the possibility of carrying out further controlled studies on a larger scale is limited by the high cost of the treatment, IVIg appears to be an effective therapy for refractory RA.
Methotrexate treatment of recalcitrant childhood dermatomyositis
Authors: Miller L. C. , Sisson B. A. , Tucker L. B. , Denardo B. A. , Schaller J. G.
Published: February 2007

Objective. To review the clinical course of 16 children with recalcitrant dermatomyositis (DM), who were treated with oral methotrexate (MTX) in addition to prednisone.

Methods. Sixteen patients with recalcitrant DM who were treated with MTX in addition to prednisone were followed between 1984 and 1990. The patients' clinical responses to treatment, including alterations in muscle strength and muscle enzyme levels, changes in prednisone dosage, and development of toxicity or complications were reviewed retrospectively.

Results. All 12 patients who received MTX for at least 8 months regained normal muscle strength. In 11 of the 12, the prednisone dosage could eventually be tapered to ⩽5 mg/day. Complications during MTX treatment required discontinuation of MTX in 5 patients, and were unrelated to the cumulative dose of the drug. Active disease recurred in 5 patients in whom MTX had been discontinued after apparent clinical remission had been achieved.

Conclusion. MTX, in combination with prednisone, is a useful adjunct in the treatment of recalcitrant childhood DM. However, recurrence of disease after withdrawal of MTX suggests that the drug may have a suppressive, rather than a remittive, effect.
Localization of tumor necrosis factor receptors in the synovial tissue and cartilage‐pannus junction in patients with rheumatoid arthritis. Implications for local actions of tumor necrosis factor α
Authors: Deleuran Bent W. , Chu Cong‐Qiu , Field Max , Brennan Fionula M. , Mitchell Tracey , Feldmann Marc , Maini Ravinder N.
Published: February 2007

Objective. We have previously described the location of tumor necrosis factor α (TNFα)–producing cells in synovial tissue and cartilage–pannus junction in rheumatoid arthritis (RA). To further understand the local actions of TNFα, we investigated the expression of TNF receptors (TNF‐R) on cells in the same compartments in patients with RA.

Methods. The expression of both p55 TNF‐R and p75 TNF‐R was determined using alkaline phosphatase–conjugated mouse anti–alkaline phosphatase (APAAP) and double immunofluorescence staining techniques with monoclonal antibodies.

Results. In RA synovial membrane, both p55 TNF‐R and p75 TNF‐R were detectable in up to 90% of the cells in the lining layer, and were demonstrated on cells in deeper layers of the membrane, including vascular endothelial cells. Cells in lymphoid aggregates expressed both TNF‐R, but with a predominant expression of p75 receptor. At the cartilage–pannus junction, the majority of pannus cells, especially those invading cartilage, expressed both the p55 and the p75 TNF‐R. Sequential section and double immunofluorescence staining showed that the TNF‐R–expressing cells were in the vicinity of TNFα‐containing cells, and some TNFα‐containing cells also expressed TNF‐R. TNF‐R–expressing cells were also detected in osteoarthritic and normal synovial tissue, but in smaller numbers and at a lower intensity.

Conclusion. These results provide histologic evidence that both p55 TNF‐R and p75 TNF‐R are expressed by a variety of cell types in RA synovial tissue, reflecting the fact that a wide range of cells are potential targets for TNFα in this tissue. This study further supports the hypothesis that TNFα plays a major role in the pathogenesis of RA.
Expression of human tenascin in synovitis and its regulation by interleukin‐1
Authors: McCachren S. Spence , Lightner Virginia A.
Published: February 2007

Objective. Tenascin is an extracellular matrix glycoprotein with effects on cell adhesion, cell migration, and lymphocyte activation. We proposed to identify the expression of human tenascin messenger RNA (mRNA) and protein in inflammatory synovitis and in normal synovium, and to identify potential regulatory cytokines.

Methods. Immunohistochemistry and in situ hybridization were used to identify the expression of tenascin in synovium. Northern blot analysis of RNA and both immunoblot analysis and enzyme‐linked immunosorbent assay of proteins were used to identify tenascin in synovial cell cultures.

Results. Tenascin was found along the synovial lining layer and in perivascular areas of normal synovium. In inflammatory synovitis, tenascin protein and mRNA expression were shown to be increased in the synovial lining layer, in perivascular areas, in lymphoid aggregates, and in areas of fibrosis. Interleukin‐1, a major mediator of tissue injury in inflammatory synovitis, induced tenascin expression and deposition in primary synovial fibroblast cultures.

Conclusion. Tenascin mRNA and protein are increased in inflammatory synovitis, and interleukin‐1 is an inducer of tenascin in synovial fibroblasts. This identifies a new pathway by which interleukin‐1 alters the extracellular matrix composition in synovitis. Since tenascin has effects on lymphocyte activation and cell adhesion, the induction of tenascin in inflammatory synovitis may play a role in the pathophysiology of arthritis.