bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlates of community resource information needs of arthritis patients
Authors: Hull Alan L. , Liebman Judith J. , Moskowitz Roland W.
Published: February 2007

One hundred eighty‐nine ambulatory arthritis patients were interviewed to assess needs for information about community resource services. Participants were asked how frequently they needed 66 specific information items. Three categories of resource needs in arthritis care were identified: general information, personal care and medical services, and assistive devices and equipment. In the first category, results indicated that the greater the impairment in functional ability, the greater the need for general information about arthritis. When functional ability was held constant, younger patients with lower family income displayed a greater need for arthritis resource information. Lower functional ability and family income were associated with a greater need for personal care and medical service information. Lower functional ability contributed the most to the need for information about assistive devices and equipment. We suggest that, as an essential component of the long‐term care of patients with rheumatic diseases, individuals who provide educational counseling should clearly understand the community resource needs of patients, and should be able to match articulated needs with the existing services. Health professionals should be aware that certain patient characteristics (specifically, family income, functional ability, and age) are related to a need for this type of information. The large percentage of patients who could not name their rheumatic disease diagnosis (65%) presents a major concern and challenge to patient educators.
Detection of anticentromere antibodies using cloned autoantigen cenp‐Bl
Authors: Rothfield N. , Whitaker D. , Bordwell B. , Weiner E. , Senecal J.‐L. , Earnshaw W.
Published: February 2007

A solid‐phase enzyme‐linked immunosorbent assay has been established using a cloned fusion protein, Cterm CENP‐B [β‐gal], as antigen. The fusion protein carries the major epitope of CENP‐B, the major centromeric autoantigen. The enzyme‐linked immunosorbent assay was more sensitive than immunofluorescence techniques in detecting anticentromere antibodies in patients with scleroderma or Raynaud'S disease, and was weakly positive in 3% of normal controls and in 3% of 70 patients with other connective tissue diseases.
A dr4‐associated dr‐dq haplotype is significantly associated with rheumatoid arthritis
Authors: Wallin Johan , Carlsson BjöUrn , Ströum HÅRkan , Möuller Erna
Published: February 2007

Forty‐three patients with seropositive, erosive rheumatoid arthritis (RA) and 24 members of 5 RA multicase families were studied for HLA class II gene polymorphism, using restriction fragment analysis with complementary DNA probes for DRβ and DQβ chains. This method generates HLA‐DR‐DQ haplotypes that are highly correlated with HLA‐DR serology. Thirty‐five of the 43 RA patients (81%) were positive for one or for both of the DR4‐associated DR‐DQ haplotypes, 4.1 and 4.2. Among these patients, the 4.1 haplotype was found significantly more often than in DR4 + controls (P < 0.01). The haplotype segment C3;B15;DR4 was present in all RA patients in 4 of the 5 families, and included the DR‐DQ4.1 haplotype.
Inhibition of in vitro proliferative response of cultured t lymphocytes to interleukin‐2 by gold sodium thiomalate
Authors: Wolf Robert E. , Hall Vicky C.
Published: February 2007

Gold sodium thiomalate (GST), in concentrations attainable during chrysotherapy for rheumatoid arthritis, significantly inhibited the proliferative responses of cultured T cells stimulated by interleukin‐2 (IL‐2). The observed suppression was not related to altered kinetics, cell death, or interference with the binding of IL‐2 to cell surface receptors. It appeared that GST affected an early step in the proliferative process, since maximum inhibition was obtained by the addition of GST within 4 hours of stimulation; progressive reduction of suppression was observed when GST was added later. Significant inhibition occurred when cultured T cells were preincubated for 24 hours with GST and washed prior to IL‐2 stimulation, although the degree of suppression was decreased. Thus, inhibitory activity was not dependent on the continued presence of GST throughout culture. These findings suggest that there is a direct inhibition of T lymphocytes by GST, which may be important in immunomodulation by gold compounds.
An enzymatically induced structural transformation in articular cartilage. its significance with respect to matrix breakdown
Authors: Broom Neil D.
Published: February 2007

It was demonstrated in this study that the 3‐dimensional, “pseudo‐random” architecture of collagen in the general matrix of normal cartilage can be transformed enzymatically into a radial array of fibril aggregates or fibers. By first degrading the proteoglycans and then attacking the collagen, it is possible to produce a collagenous structure almost identical to that observed in matrices exhibiting both nonprogressive softening and osteoarthritic changes, and in matrices subjected to dynamic overloading. This structural transformation is explained as a breakdown in the fibril interlinking system.
Anti–ro (ss‐a) antibodies from ro (ss‐a)–immunized mice
Authors: Rosario Myra O. , Fox Owen F. , Koren Eugen , Harley John B.
Published: February 2007

Immunization of BALB/c mice with immuno‐affinity‐purified bovine or human Ro (SS‐A) induces the production of antibodies reactive with Ro (SS‐A). Fusion of spleen cells from the hyperimmunized mice to SP2/0 cells resulted in hybridoma cell lines that produced anti–Ro (SS‐A) antibodies. Anti–Ro (SS‐A) binding was established by solid‐phase immunosorbent assay, immunoblotting, or RNA immunoprecipitation. Most of the anti–Ro (SS‐A) antibodies bound to both human and bovine Ro (SS‐A) in the solid phase, but only one of the monoclonal antibodies selectively bound to human Ro (SS‐A); this suggests that there are species differences between the bovine and human Ro (SS‐A) antigens. Indirect immunofluorescence studies demonstrated that most anti–Ro (SS‐A) antibodies bound to cytoplasmic or nuclear HEp‐2 cellular antigens, whereas others did not bind to fixed HEp‐2 tissue culture cells. Nuclear staining of mouse substrates by one of the sera containing anti–Ro (SS‐A) demonstrated that autoantibodies were induced by immunization with human Ro (SS‐A).
Antibodies to types i, ii, ix, and xi collagen in the serum of patients with rheumatic diseases
Authors: Charríre Guyĺne , Hartmann Daniel J. , Vignon Eric , Ronzíre Marie‐Claire , Herbage Daniel , Ville G´rard
Published: February 2007

Antibodies to native types I, II, IX, and XI collagen were measured, using a 125I‐solid‐phase radio‐immunoassay, in serum from 104 patients with rheumatic diseases (rheumatoid arthritis, osteoporosis, Paget's disease, or osteoarthritis). In all disease groups, antibodies to type II collagen occurred with greater frequency than antibodies to type I collagen (11–35% versus 5–23%). Antibodies to type XI collagen were the most frequent: They were present in ˜50% of the patients in the rheumatoid arthritis, Paget's disease, and osteoporosis groups. Antibodies to type IX collagen were found at a high frequency in the rheumatoid arthritis group only (44%). Analysis of the clinical data suggested that the presence of antibodies to collagen was associated with disease that was less severe or of shorter duration.
Interstitial pneumonitis in antinuclear antibody–negative systemic lupus erythematosus: a new clinical manifestation and possible association with anti–ro (ss‐a) antibodies
Authors: Hedgpeth Madelaine T. , Boulware Dennis W.
Published: February 2007

The clinical manifestations of patients with systemic lupus erythematosus (SLE) and negative fluorescent antinuclear antibody have been well documented. This report describes 2 cases of antinuclear antibody–negative SLE with antibodies only to Ro (SS‐A) and the previously unreported clinical manifestation of lupus interstitial pneumonitis. A review of all SLE patients from 1984–1986 with interstitial pneumonitis revealed that 10 of the 12 patients had antibodies to Ro (SS‐A). The frequency of anti–Ro (SS‐A) with interstitial pneumonitis in SLE patients suggests a possible association between the two.
Increase in levels of serum keratan sulfate following cartilage proteoglycan degradation in the rabbit knee joint
Authors: Williams James M. , Downey Colleen , Thonar EUGENE J.‐M. A.
Published: February 2007

Following injection of chymopapain into a single knee joint in rabbits, serum keratan sulfate levels rose sharply and remained elevated for at least 48 hours before returning to preinjection levels. These changes were accompanied by depletion of proteoglycans from articular cartilage in the injected joint. We conclude that serum keratan sulfate levels rise predictably following acute loss of proteoglycan from a single joint.
Frequency of infection among patients with rheumatoid arthritis versus patients with osteoarthritis or soft tissue rheumatism
Authors: van Albada‐Kuipers G. A. , Linthorst J. , Peeters E. A. J. , Breedveld F. C. , Dijkmans B. A. C. , Hermans J. , Vandenbroucke J. P. , Cats A.
Published: February 2007

We compared the frequencies and types of infections that occurred in 448 patients with rheumatoid arthritis (RA) versus those occurring in 185 control patients who had osteoarthritis or soft tissue rheumatism. At least 1 infection developed in 23% of the RA patients and in 27% of the control patients. Using a series of risk factors, we found no substantial difference in the risk of infection in RA patients compared with that in control patients. Some of these factors, such as being female, having poor functional capacity, and receiving glucocorticoid treatment, were associated with different levels of risk for infection, but the levels were similar in RA patients and control patients.
A model of health status for rheumatoid arthritis. a factor analysis of the arthritis impact measurement scales
Authors: Mason John H. , Anderson Jennifer J. , Meenan Robert F.
Published: February 2007

Health status is a key aspect of quality of life that may be addressed and affected by health care. The measurement of this construct requires the identification of unique and relevant components of health status that can be operationally defined by specific scales or scale groupings. We explored the components of health status that are operationalized by the Arthritis Impact Measurement Scales (AIMS). Prior testing has shown that the AIMS measures delineate at least 3 components of health status: Physical Function, Psychological Status, and Pain. This 3‐component model, however, can be theoretically and empirically restrictive. Using AIMS responses from a rheumatoid arthritis (RA) patient population, our investigation, through factor analyses, identifies 5 components of health status in this chronic disease: Lower Extremity Function, Upper Extremity Function, Affect, Symptom, and Social Interaction. It is proposed that these intuitively reasonable and measurable components constitute the core of the health status construct for individuals with RA. These 5 components could also prove central to the assessment of health status in other rheumatic diseases. Future studies of health status in RA should include tested measures to assess these 5 components.
What are we measuring? an examination of self‐reported functional status measures
Authors: Spiegel Jane Sinden , Leake Barbara , Spiegel Timothy M. , Paulus Harold E. , Kane Robert L. , Ward Nancy B. , Ware John E.
Published: February 2007

Functional status questionnaires are being used in various types of studies. To determine factors related to self‐reported functional ability for rheumatoid arthritis patients, we examined the relationship between a functional and mental health questionnaire and objective disease‐specific measures. Using 3–5 predictor variables, we explained 43–57% of the variance in patients' self‐reported functioning. Mental and physical health perceptions were significant predictors for each self‐reported functional measure. The relationships among mental health and self‐reported functioning should be considered when interpreting studies that use functional status questionnaires.
Aminobisphosphonate inhibition of interleukin‐1—induced bone resorption in mouse calvariae
Authors: Tan Paul L. J. , Katz June M. , Ames Ruth , Caughey David E. , Gray Harley D. , Ibbertson H. Kaye , Watson James D.
Published: February 2007

Interleukin‐1 (IL‐1) is probably an important lymphokine mediator of inflammation and bone resorption. IL‐1 derived from mononuclear cells, a melanoma cell line (MM96 cells), and recombinant human IL‐1 (rHuIL‐1β) increased in vitro bone resorption, as measured by the release of 45Ca from cultured mouse calvariae. The 50% maximum active resorption was observed with 0.125 ng/ml or approximately 10−11M rHuIL‐1β. The resorptive action of IL‐1 was not entirely dependent on prostaglandin mediation, since its effect was evident when prostaglandin synthesis was inhibited in the cultures by indomethacin. IL‐1—induced resorption has been shown to be inhibited by 10−5M 3‐amino‐1‐hydroxypropylidene‐1‐1‐bisphosphonate (APD). This inhibition was partially reversed by increasing doses of IL‐1. In vitro toxicity studies showed that at concentrations of 10−4M, APD inhibited the growth of cultured MM96, murine myelomonocytic P388D1, and rat osteosarcoma UMR 106 cells, but not other mast and lymphoid cell lines. These in vitro observations may have relevance to the use of APD in bone and joint diseases in which inflammation and bone resorption are prominent.
Interleukin‐6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides
Authors: Houssiau Frédéric A. , Devogelaer Jean‐Pierre , Damme Jo Van , Deuxchaisnes Charles Nagant De , Snick Jacques Van
Published: February 2007

Interleukin‐6 (IL‐6), also called 26‐kd protein, hybridoma plasmacytoma growth factor, β2‐interferon, or B cell stimulatory factor 2, is a recently described human cytokine with multiple growth and differentiation activities. Using a very sensitive bioassay based on the growth factor activity of this protein for B cell hybridomas, we found that IL‐6 activity was significantly elevated in synovial fluid from patients with rheumatoid arthritis (RA) or other inflammatory arthritides, as compared with that in a group of patients with osteoarthritis. Moreover, IL‐6 was detected in about one‐third of the serum samples from patients with RA. In the latter group, we found a significant correlation between serum IL‐6 activity and serum levels of C‐reactive protein, α1‐acid glycoprotein, α1‐antitrypsin, fibrinogen, and haptoglobin, which indicates that IL‐6 is related to disease activity in patients with RA.
Costochondral involvement in systemic candidiasis in heroin addicts: clinical, scintigraphic, and histologic features in 26 patients
Authors: Miro J. M. , Brancos M. A. , Abello R. , Lomena F. , Bisbe J. , Ribalta T. , Rotes‐Querol J.
Published: February 2007

We studied the clinical, scintigraphic, and histopathologic characteristics of 26 intravenous drug abusers with costochondral involvement secondary to systemic infection with Candida albicans. The clinical findings were of a mass appearing in the anterior region of the thorax. In general, signs of inflammation were absent. Histopathologic study of this costochondral mass in 12 patients showed perichondritis in 100% and myositis in 87%, with secondary involvement of cartilage in 43% and of bone in 75%. Results of bone scintigrams using 99mTc‐methylene diphosphonate were positive in only 7 of 15 patients (47%), with a correlation between positive uptake and osteitis. Gallium scintigraphy findings were positive in 9 of 10 patients (90%). The greater sensitivity of 67Ga was probably because the invariably present pericartilaginous inflammatory mass was not always accompanied by secondary cartilage and bone involvement.
Network regulation in rheumatoid arthritis. studies of dr+ t cells, anti‐dr, antiidiotypic antibodies, and clinical disease activity
Authors: Searles Robert P. , Savage Susan M. , Broz̈ek Celestyn M. , Marnell Lorraine L. , Hoffman Charles L.
Published: February 2007

We prospectively studied rheumatoid arthritis patients with various degrees of clinical disease activity, for the presence of DR+ T cells by flow cytometry, for anti‐DR using immunoblot analysis, and for antiidiotypic (anti‐id) antibodies by enzyme‐linked immunosorbent assay using F(ab′)2 monoclonal antibody anti‐DR L243 as idiotype. DR+ T cells correlated positively with anti‐DR, and anti‐id correlated negatively with both DR+ T cells and anti‐DR. Active clinical disease correlated positively with both DR+ T cells and anti‐DR, and correlated negatively with anti‐id. This DR antigen/anti‐DR/anti‐id network may control disease activity in rheumatoid arthritis patients.
The effects of leucovorin (folinic acid) on methotrexate therapy in rheumatoid arthritis patients
Authors: Tishler Moshe , Caspi Dan , Fishel Beno , Yaron Michael
Published: February 2007

High‐dose leucovorin (folinic acid) supplementation was tested in a prospective, unblinded manner for 4 weeks in 7 rheumatoid arthritis patients who were being treated successfully with low‐dose methotrexate (MTX). Nausea caused by MTX disappeared; however, the underlying rheumatic disease worsened in all patients. Subjective clinical assessment, Ritchie articular index, grip strength, erythrocyte sedimentation rate, and levels of C‐reactive protein showed statistically significant deterioration. All these parameters improved after the leucovorin was stopped. This is the first direct clinical evidence implying folate antagonism in the action of low‐dose MTX therapy in rheumatoid arthritis patients.
Complement c4b–null alleles in felty's syndrome
Authors: Thomson Wendy , Sanders Paul A. , Davis Martin , Davidson Judith , Dyer Philip A. , Grennan David M.
Published: February 2007

C4A and C4B allotypes were compared in 20 patients with Felty's syndrome (FS), 52 patients with rheumatoid arthritis (RA), and 55 control subjects. Nineteen of the FS patients had HLA–DR4. A C4B‐null allele was more frequent in the patients with FS (60%) than in either the RA patients (15%) or the control subjects (26%). Only the differences between patients with FS and those with RA remained statistically significant when DR4 positive subjects were compared. The C4B null allele may identify individuals within the rheumatoid population who are at risk of developing particular systemic complications.
Psoriatic arthritis and acquired immunodeficiency syndrome
Authors: Espinoza Luis R. , Berman Alberto , Vasey Frank B. , Cahalin Cay , Nelson Robert , Germain Bernard F.
Published: February 2007

We describe 2 patients who developed psoriatic arthritis during the course of acquired immunodeficiency syndrome. Both patients developed skin and articular involvement characteristic of psoriatic arthritis; these manifestations were refractory to conventional therapy. Our findings suggest that psoriatic arthritis should be added to the expanding spectrum of musculoskeletal manifestations of the acquired immunodeficiency syndrome.
Modulation of urokinase‐type plasminogen activator messenger rna levels in human synovial fibroblasts by interleukin‐1, retinoic acid, and a glucocorticoid
Authors: Vitti Gerard , Hamilton John A.
Published: February 2007

Previous studies have shown that mononuclear cell–conditioned medium (MCCM), interleukin‐1 (IL‐1), and all‐trans‐retinoic acid rapidly stimulate, while glucocorticoids lower, the urokinase‐type plasminogen activator (u‐PA) activity of human synovial fibroblastlike cells. It is now reported that MCCM, recombinant human IL‐1α (rHuIL‐1α), rHuIL‐1β, and all‐trans‐retinoic acid elevate the u‐PA messenger RNA (mRNA) levels to a steady‐state value within 2 hours, while dexamethasone (10−7M) inhibits this increase. For both situations, when the u‐PA activity is either stimulated or reduced, the changes in the u‐PA mRNA levels parallel the changes in the u‐PA activity, and it is suggested that modulation of gene transcription plays an important role.
Demonstration and characterization of a transient arthritis in rats following sensitization of synovial mast cells with antigen‐specific ige and parenteral challenge with specific antigen
Authors: Malone Daniel G. , Metcalfe Dean D.
Published: February 2007

We have developed a model of IgE‐dependent, mast cell–mediated arthritis in rats. One knee joint (test joint) of a Sprague‐Dawley rat was injected with 1 μg of a monoclonal IgE specific for dinitrophenol, and the contralateral (control) joint was injected with the same amount of an irrelevant monoclonal IgE in phosphate buffered saline or with phosphate buffered saline alone. Within 5 minutes of intravenous injection of antigen, an acute, transient arthritis occurred in the test joints only, with swelling and extravasation of intravascular blue dye and 125I‐labeled albumin, decreased numbers of stainable mast cells, and decreased histamine content of the joint synovium. Pretreatment of experimental animals with H1 and H2 antihistamines did not completely block the reaction. These data show that IgE‐dependent synovial mast cell degranulation causes a transient, nondestructive arthritis, reminiscent of lupus arthritis and intermittent hydrarthrosis.
Serum and plasma inhibit neutrophil stimulation by hydroxyapatite crystals. evidence that serum αl2‐hs glycoprotein is a potent and specific crystal‐bound inhibitor
Authors: Terkeltaub Robert A. , Santoro Denise A. , Mandel Gretchen , Mandel Neil
Published: February 2007

Tissue deposits of basic calcium phosphate (BCP) crystals are associated with various clinical manifestations of inflammation. We addressed the possibility that native proteins modify the ability of hydroxyapatite (HA) crystals to stimulate human inflammatory cells. Neutrophil superoxide release and chemiluminescence in response to HA crystals (0.3–4.0 mg/ml) were blunted by serum and plasma. Inhibitory activity was progressively removed from serum by sequential adsorption with HA crystals, suggesting that the inhibitors were crystal‐bound proteins. Thus, we characterized HA crystal‐bound plasma proteins by O'Farrell gels: Fibronectin, transferrin, albumin, α2−HS glycoprotein (AHSG), α1−proteinase inhibitor, α1−acid glycoprotein, Gc globulin, haptoglobin, and high density lipoprotein apolipoproteins were major bound species. Of these, AHSG was the most active inhibitor of HA‐induced neutrophil superoxide release, and this glycoprotein partially (60%) restored inhibitory activity to HA‐adsorbed serum. AHSG also bound in vitro to the related BCP crystal, octacalcium phosphate, but only minimally to calcium pyrophosphate dihydrate crystals and monosodium urate crystals. Suppressive effects on neutrophil stimulation exhibited by AHSG were also specific for BCP crystals. AHSG was present in noninflammatory synovial fluids bound to synthetic HA crystals in vitro, and AHSG could be detected on native synovial fluid HA crystals. We conclude that the binding of AHSG may modulate the inflammatory potential of BCP crystals.
High‐affinity interleukin‐2 receptors on blood lymphocytes are decreased during active rheumatoid arthritis
Authors: Emery Paul , Wood Nigel , Gentry Kay , Stockman Alex , Mackay Ian R. , Bernard Ora
Published: February 2007

The expression of receptors for interleukin‐2 (IL‐2R) was examined in patients with active or inactive rheumatoid arthritis (RA) and in control subjects. Unstimulated blood lymphocytes from patients with active RA had increased levels of total IL‐2R, as measured by Tac‐positive cells, compared with the levels found in the other 2 groups. Mitogen‐stimulated cells from patients with active RA expressed less IL‐2R per cell, but the most striking feature was the failure to express high‐affinity IL‐2R. These changes could reflect persistent antigenic stimulation and explain the defective cell‐mediated immunity in RA patients.
Giant cell inflammation compared with amyloidosis of the internal elastic lamina in temporal arteries
Authors: Muckle Thos. J.
Published: February 2007

Close examination of a series of temporal artery biopsy specimens provided histologic and statistical evidence that any association between the occurrence of giant cell arteritis and senile amyloidosis of the temporal artery internal elastic lamina is not direct, but is associated incidentally with old age. Substantial demographic differences between the 2 conditions were found; the prevalence of giant cell arteritis first waxed and then waned with increasing age, while rates for senile amyloidosis of the temporal artery progressed steadily toward 100% in the ninth decade of life.
Temporal patterns of response to d‐penicillamine, hydroxychloroquine, and placebo in juvenile rheumatoid arthritis patients
Authors: Kerckhove Catherine Van , Giannini Edward H. , Lovell Daniel J.
Published: February 2007

We calculated the time required for therapeutic benefit to become apparent following initiation of treatment with D‐penicillamine (DP), hydroxychloroquine (HCQ), or placebo (each administered concomitantly with a nonsteroidal antiinflammatory drug) using data from a double‐blind, randomized 12‐month trial in 162 patients with juvenile rheumatoid arthritis. Using previously published criteria to classify the outcome, we found that 60% of the HCQ group, 46% of the DP group, and 39% of the placebo group responded favorably after 12 months of therapy. Data from examinations between the initial and final assessments were used to determine when the response first occurred. Approximately 50% of all patients who showed improvement at 12 months had already done so by 2 months. After 6 months, 96% of the DP group, 88% of the HCQ group, and 85% of the placebo group responders had met the criteria for response. The average time until response was attained was 105 days for the DP group, 129 days for the HCQ group, and 140 days for the placebo group. Our results indicate that a favorable response to these slow‐acting antirheumatic drugs is unlikely if improvement has not occurred within the first 6 months of therapy.
Low‐dose gold compounds inhibit fibroblast proliferation and do not affect interleukin‐1 secretion by macrophages
Authors: Matsubara Tsukasa , Saegusa Yasuhiro , Hirohata Kazushi
Published: February 2007

We examined the effect of low concentrations of gold compounds on the proliferation of human fibroblasts. Gold sodium thiomalate (GST) inhibited both basal and interleukin‐1‐induced tritiated thymidine incorporation into fibroblasts in a dose‐ and time‐dependent manner. Significant inhibition was observed at the level of 5 m̈g/ml GST, and >50% inhibition was attained at 10 m̈g/ml. These concentrations are attainable in the serum of treated patients. Similar inhibition was observed when <1 m̈g/ml auranofin, which is also within a serum‐attainable range, was added. Low concentrations of GST (0–10 m̈g/ml) did not affect interleukin‐1 secretion from lipopolysaccharide‐stimulated human mononuclear phagocytes (Mϕ) when assessed by both human fibroblast and C3H/HeJ mouse thymocyte proliferation assays. When Mϕ precultured for 48 hours with GST (0–10 m̈g/ml) were added to the fibroblast culture in the presence or absence of lipopolysaccharide, there was no significant inhibition of Mϕ‐induced DNA synthesis of fibroblasts. In contrast, when fibroblasts were precultured with GST (0–10 m̈g/ml) for 48 hours and freshly separated Mϕ were added, significant inhibition was observed in Mϕ‐induced fibroblast proliferation at 5 m̈g/ml. These results suggest that low concentrations of GST directly cause a reduction of fibroblast proliferation, but do not affect the capability of Mϕ for induction of fibroblast proliferation. Therefore, gold compounds may play a role in the inhibition of the growth of rheumatoid pannus by direct inhibition of fibroblast proliferation.
Stimulation of the hyaluronic acid levels of human synovial fibroblasts by recombinant human tumor necrosis factor α, tumor necrosis factor β (lymphotoxin), interleukin‐1α, and interleukin‐1β
Authors: Butler Debra M. , Vitti Gerard F. , Leizer Tali , Hamilton John A.
Published: February 2007

Monocyte/macrophage polypeptides (monokines) alter the properties of synovial cells. This interaction could explain some of the properties of the inflamed synovium in rheumatic disease. Only recently has it been possible to test the action of purified monokines on the target synovial cells. We report here that recombinant human tumor necrosis factor α, tumor necrosis factor β (lymphotoxin), interleukin‐1α, and interleukin‐1β stimulate the hyaluronic acid (HA) levels of human synovial fibroblast‐like cells. The effect of monokines was generally inhibited by indomethacin, suggesting the involvement of an endogenous cyclooxygenase product in the stimulation, and by the glucocorticoid, dexamethasone. In contrast, all‐trans‐retinoic acid stimulated synovial cell plasminogen activator activity but did not increase the HA levels. These findings could help to explain the raised HA levels found in the joint fluids and in the circulation of patients with rheumatic disease.
Serum immunoreactive erythropoietin in rheumatoid arthritis: impaired response to anemia
Authors: Hochberg Marc C. , Arnold Cynthia M. , Hogans Beth B. , Spivak Jerry L.
Published: February 2007

Serum immunoreactive erythropoietin (EP) levels were measured in 116 patients with rheumatoid arthritis (RA) and 20 control patients with iron deficiency anemia. Serum EP levels were significantly higher in the 46 anemic RA patients than in the 70 nonanemic RA patients (mean ± 1 SD 31.0 ± 19.8 mU/ml versus 16.8 ± 12.4 mU/ml; P < 0.0001). Furthermore, although a significant inverse correlation between the serum EP level and the hemoglobin value was present in the anemic RA patients (r = −0.57, P < 0.0001), the regression coefficient describing the relationship between serum EP and hemoglobin was significantly lower for the anemic RA patients than for patients with iron deficiency anemia (F = 6.01, P < 0.025).
Effect of inhibitors of eicosanoid metabolism in murine collagen‐induced arthritis
Authors: Griswold Don E. , Hillegass Leonard M. , Meunier Paul C. , Dimartino Michael J. , Hanna Nabil
Published: February 2007

The dual inhibitors of arachidonic acid metabolism, Smith Kline & French (SK&F) 86002, SK&F 104351, and phenidone; the corticosteroid, dexamethasone; and the selective cyclooxygenase inhibitors, ibuprofen, indomethacin, naproxen, and piroxicam were evaluated for their antiarthritic potency in the murine, collagen‐induced arthritis model. The ability of these compounds to alter the severity of arthritic lesions and to reduce serum levels of the acute‐phase reactant, serum amyloid P component (SAP) were monitored. Serum concentrations of SAP were found to correlate strongly (r = 0.985) with disease severity at day 35 postimmunization. Treatment with SK&F 86002, SK&F 104351, phenidone, or dexamethasone significantly reduced disease severity, as judged by clinical score (55%, 72%, 41%, and 45% inhibition, respectively) and SAP levels (62%, 94%, 52%, and 94% inhibition, respectively) in arthritic mice. This profile of activity was not shared by the selective cyclooxygenase inhibitors, which did not uniformly inhibit disease activity by both parameters. The results suggest that dual inhibitors of 5‐lipoxygenase and cyclooxygenase may prove more effective than selective cyclooxygenase inhibitors as antiarthritic agents.
Interleukin‐1 stimulation of phospholipase activity in rat synovial fibroblasts
Authors: Godfrey Richard W. , Johnson William J. , Hoffstein Sylvia T.
Published: February 2007

Tritiated arachidonic acid (3H‐AA)—labeled rat synovial fibroblasts stimulated with human recombinant interleukin‐1β (rIL‐1β) released incorporated radiolabel in a time‐dependent and dose‐dependent manner, with labeled prostaglandins representing 29% of the released radiolabel. Treatment of the cells with dibutyryl cAMP or prostaglandin E2 enhanced both spontaneous and rIL‐1β‐induced 3H‐AA release; treatment with indomethacin or naproxen inhibited the response. The effects of these cyclooxygenase inhibitors on 3H‐AA release were not reversed by the addition of prostaglandin E2. The activities of phospholipase A, phospholipase C, and diglyceride lipase were detected in the homogenates of rat synovial fibroblasts. Pretreatment of synovial cells with rIL‐1β resulted in a threefold stimulation of phospholipase A activity and a slight increase in phospholipase C activity in cell homogenates. These data show that rIL‐1β stimulates phospholipase activities in rat synovial fibroblasts and that at least one of these activities may be regulated by either prostaglandins or cAMP.
Lipid microspherules in synovial fluid of patients with pigmented villonodular synovitis
Authors: Ugai Kazuhiro , Kurosaka Masahiro , Hirohata Kazushi
Published: February 2007

We describe 2 patients with pigmented villonodular synovitis. In both patients, synovial fluids (SF) were characterized by the presence of abundant, strongly birefringent lipid microspherules, which appeared as Maltese crosses and were found both inside foam cells and free in the SF. Histologically, the synovial membranes showed pigmented villonodular synovitis, with aggregation of foam cells containing abundant lipid microspherules in their cytoplasm. Observation of numerous birefringent lipid microspherules and foam cells in SF may be a clue to the diagnosis of pigmented villonodular synovitis.
Evaluation of clinical competence in rheumatology training programs
Authors: Harris Edward D. , Benson John A. , Blank Linda L.
Published: February 2007

To ensure that members of the public and the medical profession can identify physicians who have demonstrated excellence in the field of rheumatology, the American Board of Internal Medicine has called upon directors of rheumatology training programs to establish systems to evaluate, document, and substantiate those components of overall clinical competence that are considered essential for certification. Many of these abilities can be assessed only by repeated, direct observations.
Hepatic ultrastructure after methotrexate therapy for rheumatoid arthritis
Authors: Bjorkman David J. , Hammond Elizabeth H. , Lee Randall G. , Clegg Daniel O. , Tolman Keith G.
Published: February 2007

Twenty‐six patients receiving long‐term oral methotrexate (MTX) therapy for rheumatoid arthritis (24 patients) or psoriasis (2 patients) were prospectively evaluated for alterations in liver morphology by light microscopy, electron microscopy, and immunofluorescence microscopy. Although only 4 MTX‐treated patients had light microscopic evidence of mild fibrosis, all had evidence of collagen deposition in the space of Disse near Ito cells and changes in hepatocyte lysosomes on electron microscopy. These findings were absent from control livers. Fibrinogen, fibronectin, and type IV collagen were identified by immunofluorescence in both MTX‐treated patients and controls. We conclude that long‐term MTX therapy for rheumatoid arthritis is associated with alterations in hepatic ultrastructure, including collagen deposition in the space of Disse and changes in hepatocyte lysosomes.
Prostaglandin e2 modulation of rheumatoid factor synthesis
Authors: Alvarellos Alejandro , Lipsky Peter E. , Jasin Hugo E.
Published: February 2007

We examined the influence of prostaglandin E2 (PGE2) on the in vitro synthesis of rheumatoid factor (RF) by purified human B and T lymphocytes stimulated with Staphylococcus aureus Cowan 1 or pokeweed mitogen (PWM). Supernatants were assayed for total IgM and RF. PGE2 at concentrations of 10−7M to 10−9M significantly inhibited RF and IgM secretion stimulated by S aureus Cowan 1, a cross‐linker of B cell surface Ig. The magnitude of inhibition of RF production was significantly greater than that of total IgM at low PGE2 concentrations (P < 0.05). In contrast, PWM‐stimulated cultures were only minimally inhibited by PGE2 at all concentrations tested. Since cross‐linking of surface Ig renders B cells more susceptible to inhibition by PGE2, heat‐aggregated IgG (HAIgG) was added to the PWM‐stimulated cultures in an attempt to increase the sensitivity of precursors of RF‐secreting cells to the inhibitory effects of PGE2. Addition of HAIgG markedly increased PGE2‐mediated inhibition of RF synthesis without significantly affecting IgM production. Inhibition could not be overcome by the addition of soluble T helper cell factors, indicating that PGE2‐mediated suppression was not the result of an inhibitory action of T helper cells. When lymphocytes from patients with rheumatoid arthritis were examined, HAIgG was found to be unable to induce sensitivity to PGE2‐mediated inhibition of responsiveness. These results suggest that down‐regulation of RF synthesis requires both cross‐linking of surface Ig and the influence of PGE2. Abnormalities in this immunoregulatory mechanism may explain the ongoing production of RF in patients with rheumatoid arthritis.
Structure of t cell antigen receptor β chain in synovial fluid cells from patients with rheumatoid arthritis
Authors: Keystone E. C. , Minden M. , Klock R. , Poplonski L. , Zalcberg J. , Takadera T. , Mak T. W.
Published: February 2007

We attempted to identify a clonal proliferation of T cells from synovial fluid samples from patients with rheumatoid arthritis, using techniques of restriction fragment length polymorphism. We used probes for the β chain of the T cell receptor to analyze restriction fragments prepared from the genomic DNA of synovial fluid mononuclear cells from 10 patients and synovial fluid T cell preparations from 5 additional patients. The results demonstrated unarranged (germline) T cell receptor gene fragments of DNA in all cell preparations, indicating the lack of clonality of rheumatoid arthritis synovial fluid T cells.
Arthritogenicity of minor cartilage collagens (types IX and XI) in mice
Authors: Boissier Marie‐Christophe , Chiocchia Gilles , Ronziere Marie‐Claire , Herbage Daniel , Fournier Catherine
Published: February 2007

Native type II collagen, the major cartilage collagen, is immunogenic and arthritogenic in rodents. To investigate whether minor cartilage collagens are arthritogenic, we immunized DBA/1 mice with the pepsin‐soluble fractions of type IX or type XI collagen emulsified in Freund's complete adjuvant. Both collagens were arthritogenic in DBA/1 mice after only 1 injection. However, the incidence of the polyarthritis was lower and the severity was lesser than with that induced by bovine type II collagen, even when a booster injection was administered. All mice developed a humoral response to the immunizing antigen, without any relationship to the arthritic status. Interestingly, competition experiments showed that antibodies raised against type XI collagen also bound with high avidity to type II collagen. In contrast, sera from type IX collagen‐immunized mice did not react with either type II or type XI collagen. We conclude that types IX and XI minor cartilage collagens are both arthritogenic and immunogenic in DBA/1 mice. Whether the recognition of epitopes common to different collagens is relevant to the articular pathology remains to be elucidated.
Correlation of serologic indicators of inflammation with effectiveness of nonsteroidal antiinflammatory drug therapy in rheumatoid arthritis
Authors: Cush John J. , Lipsky Peter E. , Postlethwaite Arnold E. , Schrohenloher Ralph E. , Saway Anthony , Koopman William J.
Published: February 2007

Forty‐seven patients with rheumatoid arthritis (mean duration 5.7 years) who were receiving neither disease‐modifying drugs nor corticosteroids were enrolled in a 12‐week, multicenter study of the relationship between clinical and serologic measures of disease activity in patients taking nonsteroidal antiinflammatory drugs. After a 2‐week drug washout period, patients received flurbiprofen (200 mg/day) or sustained‐release ibuprofen (2,400 mg/day) for a 10‐week trial. Clinical response was assessed biweekly using standard clinical parameters, including 50‐foot walk time, tender joint score, duration of morning stiffness, and global assessment of disease activity and pain (by both the patient and the physician). Patients were classified as responders if there was ⩾30% improvement in at least 3 of the 4 clinical measures of disease activity. Thirty patients completed at least 8 weeks of therapy; there were 12 responders and 18 nonresponders. Of the laboratory parameters examined, the responders, but not the nonresponders, demonstrated significant reductions (from postwashout values) in levels of IgM rheumatoid factor and C‐reactive protein (CRP), along with significant increases in the number of circulating lymphocytes and decreases in the number of circulating granulocytes (P ⩽ 0.05). In contrast, the nonresponders demonstrated either no change or worsening of the laboratory correlates of disease activity. The responders also appeared to have more aggressive disease at baseline, with significantly more painful joints, greater 50‐foot walk times, elevated CRP values, and elevated erythrocyte sedimentation rates (P ⩽ 0.05). These data suggest that there is a subset of rheumatoid arthritis patients in whom clinical improvement with nonsteroidal antiinflammatory drug therapy is associated with significant reductions in IgM rheumatoid factor and CRP levels.
Abnormal t suppressor cell function in juvenile rheumatoid arthritis
Authors: Silverman Earl D. , Somma Catherine , Khan Manzoor M. , Melmon Kenneth L. , Engleman Edgar G.
Published: February 2007

The purpose of this study was to analyze T suppressor cell function in juvenile rheumatoid arthritis (JRA). JRA is a chronic inflammatory childhood disease of unknown etiology that is characterized by arthritis and immunoregulatory abnormalities. T suppressor cell precursors (CD8+, CD28−) were purified from the peripheral blood of 24 JRA patients, using a combination of monoclonal antibodies. These cells were treated with histamine or concanavalin A, agents that are known to induce suppressor activity. They were also tested for their ability to inhibit the proliferative response of autologous T cells to phytohemagglutinin. In some experiments, the accumulation of intracellular cAMP following histamine treatment was also measured. Twelve of 13 patients with clinically active JRA showed abnormal histamine‐inducible T suppressor cell function, characterized by the failure of CD8+, CD28− T cells to mediate any detectable suppression. The failure of these cells to accumulate intracellular cAMP after histamine treatment was observed in 5 of 5 patients tested who had active disease. In contrast, 11 of 11 patients with clinically inactive JRA, 5 of 5 patients with cystic fibrosis, and 9 of 9 pediatric control subjects had normal histamine‐and concanavalin A‐inducible T suppressor cell function, and a normal cAMP response to histamine. These results suggest that patients with clinically active JRA have a reversible defect in T suppressor cell function that is associated with a failure of T suppressor cell precursors to accumulate intracellular cAMP following their exposure to selected immune stimuli.
Subsequent behavior of users of an arthritis information telephone service
Authors: Maisiak Richard , Koplon Sandra , Heck Louis W.
Published: February 2007

Followup telephone interviews were conducted with a stratified random sample of 305 users of a prototype telephone information service for arthritis 2–4 months after their initial contact with the service. The percentage of respondents who reported taking at least 1 positive action for their arthritis because of service usage was 79%. The most frequently reported actions of users were asking their doctor more questions and greater compliance with their doctor's orders. About one‐half of the respondents felt more in control of their arthritis because of service usage. Both the taking of at least 1 action and the taking of certain specific actions were significantly correlated with feeling more in control of the arthritis (P > 0.01). Respondents who were less than 60 years old, black, or symptomatic were significantly more likely to take an action and took significantly more actions (P > 0.01). This minimal intervention may stimulate positive behaviors for individuals with arthritis.
Accuracy of creatinine clearance in measuring glomerular filtration rate in patients with systemic lupus erythematosus without clinical evidence of renal disease
Authors: Ratain Jill S. , Petri Michelle , Hochberg Marc C. , Hellmann David B.
Published: February 2007

We sought to determine whether creatinine clearance (Ccr) gives an accurate measurement of the glomerular filtration rate in patients with systemic lupus erythematosus (SLE) with no clinical evidence of renal disease. Eighteen such SLE patients underwent measurement of Ccr and 99mtechnetium‐DTPA clearance (CDTPA). The mean ± SD Ccr:CDTPA ratio was 1.12 ± 0.15 (95% confidence interval 1.04–1.20). These results indicate that Ccr gives an accurate measurement of the glomerular filtration rate in the majority of SLE patients who do not have clinical evidence of renal disease.
Auranofin in the treatment of juvenile rheumatoid arthritis
Authors: Giannini Edward H. , Brewer Earl J. , Kuzmina Nina , Shaikov Alexandr , Wallin Bruce
Published: February 2007

A 6‐month double‐blind, parallel, randomized, placebo‐controlled multicenter trial of auranofin (0.15–0.20 mg/kg/day) was conducted in 231 children with juvenile rheumatoid arthritis (JRA) in the United States and in the Union of Soviet Socialist Republics. Approximately 80% of the children had polyarticular disease. The auranofin‐treated patients showed greater mean decreases from baseline in 11 of the 12 articular disease indices measured than did the placebo‐treated subjects after 3 months of therapy, and in 9 of the 12 indices after 6 months. However, the actual intergroup mean differences were relatively small and were not statistically significant. According to the physician's global assessment, 69% of the auranofin‐treated patients and 61% of the placebo‐treated patients demonstrated clinically significant improvement from baseline after 6 months (P = 0.24). Children whose disease onset occurred less than 2 years prior to entry improved more than did those who had arthritis for a longer period. In addition, those with polyarticular involvement at baseline improved more than did patients with mild disease. However, these relationships were observed in both the auranofin‐ and placebo‐treated groups, and again, there were no significant intergroup differences. Diarrhea was the most common adverse effect of auranofin. We conclude that the clinical efficacy of auranofin is modestly higher than that of placebo in the treatment of JRA, as evidenced by the consistent trends observed in the data. However, the magnitude of the individual intergroup differences is not statistically significant. Auranofin appears to be very safe in children with JRA.