bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibronectin in acute and chronic inflammation
Authors: Stecher Vera J. , Kaplan John E. , Connolly Kevin , Mielens Zigurd , Saelens Jeffrey K.
Published: February 2007

Recent evidence suggests that fibronectin (Fn), a high molecular weight glycoprotein, may be used as an indicator protein in rats with adjuvant‐induced arthritis. Rocket immunoelectrophoresis, using purified goat anti‐rat Fn, provided a specific and sensitive means of measuring plasma Fn in rats during the development of various inflammatory disease states. It was shown that normal rat plasma Fn levels of approximately 400 μg/ml double within 24 hours after injection of adjuvant. Plasma Fn levels in this model of chronic systemic inflammatory joint disease were tracked for more than 4 months and remained significantly higher than normal. On the other hand, a carrageenan‐induced inflammatory response in the pleural cavity of rats resulted in a large local accumulation of leukocytes, but no change in plasma Fn levels. A carrageenan‐induced model of acute inflammation resulted in increased paw swelling within 6 hours and enhanced plasma Fn levels within 24 hours; plasma Fn levels returned to normal within 1 week. Quantitation of plasma Fn levels in the rat may provide a useful biochemical parameter for the study of chronic systemic inflammatory diseases.
A multicenter study of annual health service utilization and costs in rheumatoid arthritis
Authors: Lubeck Deborah P. , Spitz Patricia W. , Fries James F. , Wolfe Frederick , Mitchell Donald M. , Roth Sanford H.
Published: February 2007

The economic impact of chronic illness has important implications for medical practice and health policy. To determine the yearly costs of illness for those who have rheumatoid arthritis, a detailed, self‐administered questionnaire was developed. The questionnaire was completed by 940 patients. Direct costs (recorded as charges) include the average annual expenditures by all patients and third party payers for: hospital care ($913), physician costs ($206), other health professional visits ($71), medications ($436), laboratory tests ($217), radiographs ($116), assistive devices ($24), and nontraditional therapies ($22). The total annual medical costs per patient were $2,533. In a multivariate analysis that controlled for age, sex, education, and disease duration, the outpatient costs, inpatient costs, and total costs were all positively related to the Health Assessment Questionnaire Disability Index (P f < 0.01) and global health (P f < 0.01), but were not associated with self‐reported pain.
Induction of lupus inclusions by sera from patients with systemic lupus erythematosus
Authors: Rich Steven A. , Owens Timothy R. , Anzola M. Cristina , Bartholomew Lee E.
Published: February 2007

A sensitive in vitro bioassay for the α‐interferon induction of lupus‐type inclusions (LI) has been established with the human B lymphoblastoid cell line, Daudi. Sera from 11 patients with systemic lupus erythematosus (SLE) were evaluated with this assay. LI induction by these sera increased in proportion to their antiviral activity on Madin‐Darby bovine kidney (MDBK) cells. Two of these sera did not induce LI; they showed no antiviral activity on the MDBK cell assay. Clinically and serologically, their donors were in remission. Two sera induced the formation of LI that exceeded the maximum frequencies obtained with 3 α‐interferon preparations. These sera had the greatest antiviral activities, and their donors had the greatest disease activities. Antisera to α‐interferons prevented the induction of LI with the pure and homogeneous recombinant human leukocyte interferon, IFLrA, and SLE sera. Together, these results provide evidence that the α‐interferon endogenous to SLE patients has a great ability to induce LI, and the SLE serum induction of LI corresponds well to the patient's disease activity.
Bronchiolitis in a rheumatoid arthritis patient receiving auranofin
Authors: O'Duffy J. Desmond , Luthra Harvinder S. , Unni K. Krishnan , Hyatt Robert E.
Published: February 2007

A patient with severe rheumatoid arthritis and sicca symptoms was treated with auranofin. During auranofin therapy, she developed irreversible airways obstruction due to bronchiolitis. Whereas this complication could have been due to her underlying disease, we discuss here the possibility of its being related to the auranofin therapy.
Adult sporadic hypophosphatemic osteomalacia presenting as regional migratory osteoporosis
Authors: Gerster Jean‐C. , Jaeger Philippe , Gobelet Charles , Boivin Georges
Published: February 2007

Osteoarticular manifestations associated with adult sporadic renal phosphate diabetes have previously been reported. We describe a 36‐year‐old man with phosphate diabetes who presented with migratory regional osteoporosis of the lower limbs. Our data suggest a cause‐effect relationship between regional migratory osteoporosis and adult phosphate diabetes.
Liposome‐induced synovitis in rabbits: Light and electron microscopic studies
Authors: Choi Sung Jae , Schumacher H. Ralph , Clayburne Gilda , Rothfuss M. Susan , Sieck Marie
Published: February 2007

A solution containing synthetic liposomes was injected into rabbit knee joints. This induced light and electron microscopic findings very similar to those seen in acute or chronic arthritis, not attributable to any mechanism other than to spherulites, in humans. Synovial fluid studies revealed leukocytosis and abundant extracellular, and/or intracellular positively birefringent spherulites, which appeared as Maltese crosses. Histologic studies of synovial membranes showed infiltration with polymorphonuclear neutrophils or mononuclear cells. Examination of the synovial fluids and synovial membranes by electron microscopy revealed intracellular multilayered membranous arrays of varying shapes. These observations suggest that further consideration should be given to a phlogistic role for similar spherulites found in some patients.
Reflex sympathetic dystrophy syndrome: An unusual mode of presentation of osteomalacia
Authors: Huaux J. P. , Malghem J. , Maldague B. , Devogelaer J. P. , Esselinckx W. , Withofs H. , De Deuxchaisnes C. Nagant
Published: February 2007

We report 2 patients with reflex sympathetic dystrophy syndrome (RSDS) associated with renal tubular osteomalacia. In both patients, RSDS was the presenting manifestation. Treatment of the underlying condition with calcitriol resulted in healing in both patients. These cases prompted us to undertake a retrospective study of 24 consecutive patients with osteomalacia (6 of renal tubular origin, 18 related to vitamin D deficiency), and of 259 consecutive patients with RSDS. Among those with osteomalacia, radiologic lesions strongly suggestive of RSDS were found in 5 patients (21%), 4 of whom had renal tubular defects, and only 1 had vitamin D deficiency. In the group with RSDS, 1 patient (0.4%) was found to have osteomalacia of renal tubular origin. Thus, radiologic findings suggestive of RSDS are frequent in patients with osteomalacia, especially that of renal tubular origin. On rare occasions, the full‐blown clinical picture of RSDS may obscure the diagnosis of osteomalacia.
Cost‐effectiveness of total joint arthroplasty in osteoarthritis
Authors: Liang Matthew H. , Cullen Karen E. , Larson Martin G. , Thompson Mark S. , Schwartz Julie A. , Fossel Anne H. , Roberts William N. , Sledge Clement B.
Published: February 2007

Although total joint replacement (TJR) is a major advance in the treatment of patients with osteoarthritis, its cost‐effectiveness has been questioned. We report the results of a study of the costs and benefits of TJR in consecutive osteoarthritis patients, 6 months after the surgery. Health status was measured by the Index of Well‐Being. Costs of services for arthritis were determined by interview and billing records. Six months after TJR, significant improvements were seen in global health and in functional status. The average cost of care for the 6 months prior to TJR was $933. The average cost during the 6 months beginning with the TJR was $22,730 per patient—due almost entirely to costs of surgery. In general, the surgery did not change work status, probably because the mean age of the patients was 66.4 years. There were large effectiveness/cost differential, (the larger the effectiveness/cost differential, the higher the degree of cost‐effectiveness [CE]). At 6 months, for all patients, the CE was associated with initial health status. The highest CE was observed in 10 patients who initially had the poorest health. TJR is more cost‐effective for patients with the most to gain and less effective for those with better preoperative health status.
HLA‐DP antigens in patients with pauciarticular juvenile rheumatoid arthritis
Authors: Hoffman Robert W. , Shaw Stephen , Francis Lynn C. , Larson Martin G. , Petersen Robert A. , Chylack Leo T. , Glass David N.
Published: February 2007

The distribution of the recently described HLA‐DP antigens was examined in a population of patients with pauciarticular juvenile rheumatoid arthritis and iridocyclitis, in an attempt to further characterize the immunogenetically determined susceptibility to this disease. There was a significantly increased frequency of the HLA‐DPw2 antigen in the patients compared with the controls (67% versus 34%; odds ratio 3.9, P = 0.003 by Fisher's exact test). Population studies and family studies showed that this association with HLA‐DPw2 was not secondary to linkage disequilibrium with the previously defined HLA‐D region markers of disease (HLA‐DR5 and HLA‐DRw8) in these patients. These data raise the possibility that susceptibility to this form of juvenile rheumatoid arthritis may be regulated by more than one HLA‐linked gene.
Evidence that interleukin‐1 induction of synovial cell plasminogen activator is mediated via prostaglandin E2 and cAMP
Authors: Mochan Eugene , Uhl Joanne , Newton Robert
Published: February 2007

Addition of the cyclooxygenase inhibitor indomethacin to human synovial cells in culture, at concentrations which completely block prostaglandin E2 (PGE2) synthesis, reversibly inhibited the interleukin‐1 (IL‐1) stimulation of cell‐associated and extracellular plasminogen activator (PA) production. Results of mixing experiments suggested that the inhibition by indomethacin was not due to stimulation of production and/or activation of a PA inhibitor, but reflected inhibition of PA synthesis. Simultaneous addition of PGE2 or dibutyryl cAMP prevented the inhibition by indomethacin. Addition of the phosphodiesterase inhibitor, theophylline, the adenylate cyclase stimulator, forskolin, or dibutyryl cAMP caused an enhancement of the IL‐1 induction of synovial cell PA. These results suggest that the IL‐1 induction of synovial cell PA occurs via generation of endogenous PGE2 and cAMP.
Wegener's granulomatosis in the elderly
Authors: Weiner Steven R. , Paulus Harold E. , Weisbart Richard H.
Published: February 2007

Wegener's granulomatosis is a systemic necrotizing granulomatous vasculitis in which the average age at onset is in the forties. The disease has an excellent response to treatment with cyclophosphamide. We proposed that the tendency to accept multisystem disease in elderly patients (≥60 years old) and a reluctance to administer aggressive therapy would be reflected in the diagnosis and treatment of Wegener's granulomatosis in the elderly, and that as a consequence, the delay in diagnosis and implementation of therapy could result in a needlessly higher morbidity and mortality rate for this population of patients.
Development of severe limited scleroderma in complicated Raynaud's phenomenon after limb immobilization: Report of two cases and study of collagen biosynthesis
Authors: Varga John , Jimenez Sergio A.
Published: February 2007

We describe 2 patients with Raynaud's phenomenon who developed severe sclerodermatous changes after immobilization. The scleroderma was confined to the immobilized limb. Histologic examination of tissue samples of the affected skin showed mononuclear cell infiltrates and marked collagen deposition in the dermis and subcutaneous adipose tissue. In vitro biosynthetic studies demonstrated a dramatic increase in collagen production by cultures of involved skin from one of the patients. These results suggest that immobilization resulted in activation of dermal fibroblasts (perhaps mediated by inflammatory cells) and in the subsequent development of fibrosis in both of these patients.
Rat cytomegalovirus infection enhances type II collagen arthritis in rats
Authors: Smith Charles B. , Griffiths Marie M. , Wei Lian S.
Published: February 2007

The effect of rat cytomegalovirus (RCMV) infection on type II collagen‐induced arthritis was studied in DA rats. Rats were infected with RCMV 5 days before, simultaneously with, or 5 days after immunization with calf type II collagen. Control rats were either given type II collagen alone or were injected with normal rat salivary gland (NRSG) simultaneously with collagen immunization. Severity of arthritis in each limb was graded on a scale of 1–4 (maximum score 16). In 5 experiments, peak arthritis scores in the RCMV groups were twice those of the control groups which received NRSG or collagen only (8–9 versus 4–6). Radiographs of involved joints showed greater destruction of cartilage and articular bone in the RCMV rats than in the NRSG control group. Repeated attempts to culture RCMV from joint tissues were unsuccessful. Our results indicate that RCMV infection enhances the arthritic process in this experimental model of an autoimmune arthritis.
Complement activation in synovial fluid and tissue from patients with juvenile rheumatoid arthritis
Authors: Mollnes Tmo Eirik , Paus Albert
Published: February 2007

Synovial fluid (SF) and synovial tissue from 10 patients with juvenile rheumatoid arthritis were examined. The SFs were heterogeneous with respect to the degree of complement activation. Quantification of C3dg and the terminal complement complex revealed a positive correlation between activation of the early and the late parts of the cascade in all patients. The amount of C‐reactive protein and the number of white blood cells in the SF correlated significantly with the degree of complement activation. Weak deposits of C3, C3dg, or terminal complement complex were observed in a few vessels in the synovial tissue from 5 of the patients. There was no correlation between complement activity in SF and in the corresponding tissue. Furthermore, there was no correlation between clinical activity in the joints and the degree of complement activation. It is concluded that there is a discrepancy between synovial tissue and synovial fluid with respect to complement activation. C‐reactive protein may, to some extent, be responsible for activation in SF, and the accumulation of white blood cells may be due to complement activation products.
A double‐blind, placebo‐controlled trial
Authors: Pinals Robert S. , Kaplan Stanley B. , Lawson Jeffrey G. , Hepburn Bonnie
Published: February 2007

Sulfasalazine (SSZ), 3 gm daily, was compared with placebo for treatment of rheumatoid arthritis, in a 15‐week randomized, parallel, double‐blind trial. Joint tenderness and swelling, morning stiffness, grip strength, and pain score all showed significantly more improvement with SSZ than with placebo. Adverse effects, particularly gastrointestinal reactions, led to withdrawal from the study of 28% of the patients who had been receiving SSZ, but these effects were all readily reversible and not life‐threatening. These results confirm previous findings that suppression of rheumatoid synovitis may be induced by SSZ, within 2 months after full maintenance doses are reached.
Modulation of spontaneous immunoglobulin production by natural killer cells in rheumatoid arthritis
Authors: Tovar Zair , Pope Richard M. , Talal Norman
Published: February 2007

Synovial fluid (SF) mononuclear cells obtained from patients with rheumatoid arthritis (RA) spontaneously produce large amounts of immunoglobulin. In the rheumatoid joint, natural killer (NK) cell activity is reduced in comparison with that in the peripheral blood (PB). We examined the ability of SF NK cells to modulate the spontaneous production of Ig in RA SF, and we contrasted this with the activity in PB from RA patients and from normal subjects. We found that the spontaneous production of IgG was greater in RA SF than in RA or normal PB. The baseline NK activity was significantly lower in RA SF than in RA or normal PB (P < 0.005). Incubation with anti‐Leu‐11b and complement reduced NK activity in PB, but not in SF, and it significantly (P ⩽ 0.021) increased IgG production in both RA SF and RA PB. Lysis of NK cells in this manner also resulted in a significant increase (P < 0.02) in IgM production in RA SF. These results suggest that NK cells with a Leu‐11b phenotype down‐regulate the ongoing synthesis of IgG and IgM in the rheumatoid joint.
Linkage studies of hla and rheumatoid arthritis in multicase families
Authors: Walker D. J. , Burn J. , Griffiths I. D. , Roberts D. F. , Stephenson A. M.
Published: February 2007

The linkage of rheumatoid arthritis (RA) to the HLA–DR locus was investigated in 17 families with multiple cases of RA. Log odds scores were computed using the Liped program; sibship associations were examined by 2 methods. The results showed a trend toward linkage which was short of significance. The results were similar for patients with classic or definite RA, with or without the inclusion of probable RA patients. The finding of strong association and weak linkage would suggest that it is DR4, itself, that is important in RA.
Inhibitor of interleukin‐2 in rheumatoid synovial fluid
Authors: Miossec Pierre , Kashiwado Takamichi , Ziff Morris , Smith Ashbel
Published: February 2007

Although large numbers of T cells infiltrate the synovium of patients with rheumatoid arthritis (RA), the responses of these cells, as present in the blood and synovial fluid (SF), to exogenous interleukin‐2 (IL‐2) and their production of IL‐2 are diminished. To investigate this functional defect, RA SF were examined for the presence of inhibitors of IL‐1 and IL‐2. A factor was found which inhibited the IL‐2–induced proliferation of mitogen‐stimulated human T cells and the IL‐1–induced proliferation of C3H/Hej mouse thymocytes, but not IL‐1–induced fibroblast proliferation. On AcA 54 Ultrogel filtration, the inhibitory activity resided in a fraction with an apparent molecular weight of >70 kd and a major pI of 6.8. The inhibitory effect of RA SF on lymphocyte proliferation was partially corrected with IL‐2, but not with IL‐1. In the presence of RA SF, normal lymphocytes showed not only a decreased response to exogenous IL‐2, but also a decreased production of IL‐2. The presence of an inhibitor of IL‐2 in RA SF could contribute to the IL‐2–related T cell defects observed in RA.
Assessment of kininases in rheumatic diseases and the effect of therapeutic agents
Authors: Sheikh Iftikhar A. , Kaplan Allen P.
Published: February 2007

Bradykinin is degraded in human plasma by a carboxypeptidase to yield desArg9‐bradykinin (DBK) which is then digested by angiotensin‐converting enzyme (ACE) to the pentapeptide Arg‐Pro‐Pro‐Gly‐Phe and the tripeptide Ser‐Pro‐Phe. We have studied the rate of kinin degradation by each of these enzymes in patients with rheumatoid arthritis (RA) and with systemic lupus erythematosus (SLE), compared with the degradation rate in degenerative joint disease and normal subjects. Carboxypeptidase activity was the same in all individuals, but ACE activity was increased in the RA and SLE patients. We examined the effects of aspirin, sodium salicylate, auranofin, penicillamine, and corticosteroids on kinin metabolism, and all of these were marked inhibitors of ACE; however, only penicillamine had any demonstrable inhibition of carboxypeptidase. These observations suggest rapid degradation of DBK in patients with untreated RA and SLE, whereas drugs utilized in therapy have the opposite effects. Studies to examine the role of DBK in disease manifestations are in progress.
Adult‐onset still's disease
Authors: Cush John J. , Medsger Thomas A. , Christy Wallace C. , Herbert David C. , Cooperstein Lawrence A.
Published: February 2007

We reviewed the long‐term natural history of 21 adult‐onset Still's disease patients. Patient subsets were identified according to clinical course patterns. These included monocyclic systemic disease in 4, polycyclic systemic disease in 2, chronic articular monocyclic systemic disease in 10, and chronic articular polycyclic systemic disease in the remaining 5 patients. Functional outcome differed according to course patterns and the extent of articular involvement. Systemic manifestations, per se, did not contribute to poor functional prognosis. Chronic articular disease had the worst outcome: 27% evolved to functional class III status, compared with none in the cyclic systemic groups. Those patients who had a chronic articular pattern or a polyarticular onset and course were at higher risk to develop disabling arthritis. An aggressive approach to therapy, including the early use of remittive agents, should be considered in these patient subsets.
Drug‐induced peripheral neuropathy in a patient with psoriatic arthritis
Authors: Rothenberg Ralph J. , Sufit Robert L.
Published: February 2007

A patient with psoriatic arthritis developed a peripheral neuropathy while taking hydroxychloroquine and naproxen. Although it was initially suspected that hydroxychloroquine was responsible for the neuropathy, subsequent rechallenge with naproxen demonstrated that clinical and electrophysiologic findings were related to routine pharmacologic doses of naproxen.
Airways disease in rheumatoid arthritis patients
Authors: Radoux V. , Méanard H. A. , Béagin R. , Déacary F. , Koopman W. J.
Published: February 2007

Airflow limitation is a frequent finding in patients with rheumatic diseases. We have previously suggested that it is associated with autoimmune exocrinopathy in Sjögren's syndrome. To compare clinical features of patients with and without airways dysfunction and to further test the hypothesis of a link between airways disease and exocrinopathy, we prospectively studied 2 groups of 15 lifetime nonsmoker female patients with seropositive rheumatoid arthritis (RA). The 2 groups were similar in their clinical and immunologic features, but differed in terms of airways function. Salivary, lacrimal, and sweat gland dysfunction were significantly more prevalent or severe in the group with airways disease. Antinuclear antibodies were also more prominent in the patients with airways disease, but antibodies against RNP, SS‐A, SS‐B, and double‐stranded DNA were not present in these patients. HLA‐DR4 was found in 80% of the RA patients with airways disease and in 57% of those without airways disease. HLA–B8 and DR3 were equivalently distributed in both groups. This prospective study further documents the existence of small airways disease in RA and supports the view that autoimmune exocrinopathy predisposes to its expression.
IgM rheumatoid factor plaque‐forming cells in juvenile rheumatoid arthritis
Authors: Moore Terry L. , El‐Najdawi Eva , Dorner Robert W.
Published: February 2007

Using a direct, plaque‐forming cell (PFC) assay with sensitized sheep erythrocytes, lymphocytes that secrete IgM rheumatoid factors (RF) have been detected in the peripheral blood of patients with juvenile rheumatoid arthritis. Of 15 juvenile rheumatoid arthritis patients tested, 8 were seropositive and 7 were seronegative, but 6 of the seronegative patients had hidden 19S IgM‐RF. Ten patients (5 seropositive and 5 with hidden 19S IgM‐RF) demonstrated RF‐PFC in their peripheral blood (range 15 to >200 RF‐PFC/106 mononuclear cells). Of 11 patients who had active disease, 10 had RF‐PFC, and the 4 patients who had inactive disease had no PFC in their peripheral blood. HLA typing of all 15 patients revealed no correlation between the presence of RF‐PFC and HLA type.
Mseleni disease serum is not harmful to cultured chondrocytes
Authors: Changlong Yu , Fincham John E. , Wright George C. , Taljaard Joshua J. F. , Sokoloff Leon
Published: February 2007

The origins of Mseleni disease, an acquired polyarticular degenerative joint disease, are unknown. We examined sera from 12 patients with the disease, 5 unaffected Mseleni residents, and 5 Durban residents. The effects of sera from the 12 patients with Mseleni disease on DNA or sulfated proteoglycan synthesis by cultured rabbit or human infant articular chondrocytes were no different from those of control sera. Cells derived from 2 children contained no stainable DR antigens; coculture had no impact on either of the above measures of cell function.
Procollagen gene expression by scleroderma fibroblasts in culture. inhibition of collagen production and reduction of proα(i) and proα1(III) collagen messenger RNA steady‐state levels by retinoids
Authors: Ohta Akihide , Uitto Jouni
Published: February 2007

Recent studies have demonstrated that retinoids (synthetic vitamin A analogs) can modulate connective tissue metabolism in human skin fibroblast cultures. In this study, we examined the effects of 3 retinoids, all‐trans‐retinoic acid (RA), 13‐cis‐RA, and an aromatic retinoid, RO‐10–9359, on collagen gene expression in scleroderma fibroblast cultures and matched control fibroblast cultures. The results indicated that all‐trans‐RA and 13‐cis‐RA significantly reduced procollagen production both in control and scleroderma fibroblast cultures in a dose‐dependent manner. The reduction in procollagen production was paralleled by a similar decrease in steady‐state levels of type I and type III procollagen messenger RNAs, which suggests that there is coordinate inhibition on the transcriptional level. In contrast, RO‐10–9359 elicited only limited effects on collagen production, and such effects were variable. The results suggest that further development of retinoids might provide an effective means to counteract tissue deposition of collagen in scleroderma and other fibrotic diseases.
Successful joint arthroplasty following proteus morganii (morganella morganii) septic arthritis: a four‐year study
Authors: Katz Linda M. , Lewis Randall J. , Borenstein David G.
Published: February 2007

Proteus morganii (Morganella morganii) is an uncommon cause of septic arthritis. We describe a 53‐year‐old woman with severely deforming rheumatoid arthritis, who developed an indolent septic arthritis secondary to infection with this organism. She was treated with antibiotics and closed drainage, and subsequently, underwent successful arthroplasty. She continues to do well 4.5 years later. This patient's disease course shows that gram‐negative septic arthritis, effectively treated, does not preclude successful total joint arthroplasty.
Rheumatoid nodules of the spine: case report and review of the literature
Authors: Pearson Mark E. , Kosco Mary , Huffer William , Winter William , Engelbrecht James A. , Steigerwald James C.
Published: February 2007

We present the case of a patient who had rheumatoid nodules of the vertebrae, which had resulted in bony destruction of the spine at 3 levels. Although there have been only 3 previous reports of such findings with confirmation by histologic analysis, we believe the condition is more common than has been thought. From a review of the literature, we found that similar clinical and radiographic features, as well as descriptions of rheumatoid granulation tissue invading the disc spaces, have been described in several subjects.
Stimulation of b cell differentiation by adherent mononuclear cells in systemic lupus erythematosus
Authors: Jandl Robert C. , Adirim Terry A. , Schur Peter H.
Published: February 2007

We studied B cell proliferation and differentiation in response to factors released by adherent monocytes in patients with systemic lupus erythematosus (SLE). Adherent cell supernatants (ACS) were added to peripheral blood mononuclear cells, and the effects on IgG synthesis, the number of Ig‐secreting cells (ISC), and proliferation were determined. Exposure of SLE mononuclear cells to autologous ACS caused an increase (approximately twofold) in IgG production and ISC numbers. In contrast, exposure of normal mononuclear cells to autologous ACS did not significantly increase IgG production or ISC numbers. Addition of SLE ACS to cultures of normal mononuclear cells did not stimulate ISC production. There was no significant level of 3H‐thymidine uptake by cultures of SLE or normal mononuclear cells in response to either SLE or normal ACS. In the presence of an excess number of autologous T cells, ACS stimulation of IgG synthesis was further enhanced. These findings indicate that adherent monocytes contribute to B cell hyperactivity in SLE by stimulating B cell differentiation. SLE mononuclear cells appear to be more responsive to ACS stimulation than are normal mononuclear cells.
Histopathology of arthritis induced in rats by active immunization to mycobacterial antigens or by systemic transfer of t lymphocyte lines. a light and electron microscopic study of the articular surface using cationized ferritin
Authors: Stanescu Ritta , Lider Ofer , Eden Willem Van , Holoshitz Joseph , Cohen Irun R.
Published: February 2007

We analyzed the histopathologic findings of arthritis in 3 rat models: adjuvant arthritis induced by active immunization to Mycobacterium tuberculosis (MT) antigens, arthritis produced by passive transfer of an intrinsically arthritogenic line of anti‐MT T lymphocytes, and bystander arthritis produced by intra‐articular injection of a foreign antigen, ovalbumin, into rats with T lymphocyte line cells specific for the ovalbumin antigen. The histopathology of the tibiotarsal and knee joints was studied by light microscopy and the articular surface of the cartilage by electron microscopy after labeling with cationized ferritin. The lesions in the 3 models of arthritis were compared. In active adjuvant arthritis, inflammatory lesions and cartilage destruction were found as early as 9 days after immunization, and persisted for as long as 11 months. Similar, but somewhat milder, lesions were found in arthritis produced by transfer of anti‐MT T lymphocytes. Inflammatory signs were present at 4 days, when there was no evidence of joint edema. Severe inflammatory lesions were found in arthritis induced by transfer of anti‐ovalbumin T lymphocytes that was followed by ovalbumin injection into the knee. Pathologic changes were found to be similar in all 3 models. Thus, the changes could be attributed to the action of T lymphocytes, irrespective of whether the target antigen was intrinsic to the joint.
High levels of in vitro igm rheumatoid factor synthesis correlate with hla–dr4 in normal individuals
Authors: Olsen Nancy J. , Stastny Peter , Jasin Hugo E.
Published: February 2007

The association between the HLA–DR4 histocompatibility antigen and in vitro synthesis of IgM and IgM rheumatoid factor (IgM‐RF) by blood mononuclear cells was investigated in 35 normal subjects. In vitro cultures of T and B cells were stimulated with pokeweed mitogen, and the secreted IgM‐RF, tetanus antibody, and total IgM protein were measured by solid‐phase radioimmunoassay. In cultures containing unseparated T cells, IgM‐RF production in the DR4+ and DR4–subgroups was not significantly different. However, depletion of OKT8+ cells containing T suppressor cells resulted in significantly higher IgM and IgM‐RF synthesis in the DR4+ subgroup. Moreover, 6 of the 8 highest levels of IgM‐RF were produced by DR4+ individuals, while only 7 of the remaining 27 individuals were DR4+ (P = 0.035). Ratios of secreted IgM‐RF : IgM indicated that there was a relative enrichment for IgM‐RF–specific B cell precursors in DR4+ high responders, although total numbers of circulating B cells were not increased. High responder B cells had high levels of responsiveness when mixed with T helper cells from low responders, whereas low responder B cells consistently produced low responses, even when cocultured with T helper cells from high responder donors. The data suggest that a subset of normal individuals has a pokeweed mitogen–responsive lymphocyte population that contains a B cell subpopulation specific for IgM‐RF synthesis and that this condition is associated with HLA–DR4. In certain individuals who have the DR4 type, there may be a component of a susceptible genetic background, upon which other factors act to induce IgM‐RF synthesis and which may produce clinical manifestations of rheumatoid arthritis.
Peripheral blood and synovial fluid monocyte activation in inflammatory arthritis. ii. low levels of synovial fluid and synovial tissue interferon suggest that γgm‐interferon is not the primary macrophage activating factor
Authors: Firestein Gary S. , Zvaifler Nathan J.
Published: February 2007

Because synovial fluid monocytes (SFM) in patients with inflammatory arthritis bear an activated phenotype (i.e., high expression of HLA–DR and low expression of the monocyte differentiation antigen Mo2), we assessed the role of γ‐interferon (γ‐IFN) in the activation of these cells. Sensitive and specific radioimmunoassays detected only 0.40 ± 0.20 units/ml of γ‐IFN in the SF of patients with rheumatoid arthritis (RA) and 0.61 ± 0.67 units/ml of γ‐IFN in the SF of patients with other forms of chronic inflammatory arthritis. There was no detectable α‐IFN in any SF studied by radioimmumoassay. Bioassays failed to detect nonimmunoreactive IFN. Synovial tissue (ST) explants produced very little γ‐IFN (0.14 ± 0.091 units/ml), and production was not increased by the presence of indomethacin in the cultures or by removal of adherent cells. However, γ‐IFN was produced if ST was cultivated in the presence of phytohemagglutinin. In SF and ST supernatants, γ‐IFN‐mediated induction of HLA–DR on monocytes was inhibited, even though the amount of immunoreactive IFN was not affected. Prostaglandin E2 was shown to be one possible inhibitor. We demonstrated that a factor that induces HLA–DR on some individuals' peripheral blood monocytes, and cannot be neutralized by monoclonal anti–γ‐IFN antibody, is present in SF and ST supernatants. These data suggest that activation of SFM may occur by mechanisms other than γ‐IFN.
Plasma from rheumatoid arthritis patients does not contain abnormally high levels of α2‐macroglobulin–proteinase complexes
Authors: Davies M. Elisabeth , Coughlan R. , Barrett Alan J.
Published: February 2007

We measured the levels of α2‐macroglobulin (α2M)–proteinase complexes in the plasma of 18 patients with classic rheumatoid arthritis, 11 age‐matched patients with noninflammatory back pain and osteoarthritis, and 8 healthy volunteers. In contrast with previous reports, we found no evidence of α‐proteinase complexes in the plasma samples from individuals in any of the groups. In our assays, all activity that might have been the result of the presence of such complexes in the plasma samples proved instead to be an artifact attributable to contamination of the anti–α2M antibody immobilized on the AffiGel solid phase with a trypsin‐like proteinase. When the contaminating activity was eliminated by pretreatment of the antibody with 1 mM diisopropyl fluorophosphate, no degradation of substrate was detected with any of the plasma samples. However, the ability of the solid‐phase assay to detect and quantitate α2M‐proteinase complexes when they are present was confirmed in control experiments with plasma samples to which preformed α2M‐trypsin complexes had been added, or in which α2M‐kallikrein complexes had been generated by activation of Hageman factor (coagulation factor XII). We therefore conclude that neither normal plasma nor that from rheumatoid arthritis patients contains measurable amounts of α2M‐proteinase complexes.
A low molecular weight, heat‐labile factor enhances neutrophil fc receptor–mediated lysosomal enzyme release and phagocytosis
Authors: Blackburn Warren D. , Heck Louis W. , Koopman William J. , Gresham Hattie D.
Published: February 2007

When exposed to solid‐phase immune complexes, polymorphonuclear neutrophils (PMN) degranulate and release proteases capable of degrading the major structural macromolecules of the joint. Evidence indicates that the PMN response to such activators may be modified by factors present at the sites of inflammation. We have evaluated the effects of a low molecular weight factor present in synovial fluid from rheumatoid arthritis (RA) patients on Fc receptor‐mediated PMN degranulation and phagocytosis. Synovial fluid samples from 11 RA patients were studied; 10 of them contained factor(s) which augmented phagocytosis and degranulation mediated through the Fc receptor. This factor(s) alone, however, did not initiate neutrophil degranulation: its MW is less than 10,000 daltons and it is unstable when heated to 56°C. We also examined supernatants that were produced by coculturing adherent human mononuclear cells stimulated by IgG‐coated sheep red blood cells with autologous nonadherent mononuclear cells. A factor(s) with properties similar to those found in the synovial fluids (i.e., heat‐labile at 56°C and capable of augmenting Fc receptor‐mediated degranulation and phagocytosis) was found in the stimulated human mononuclear cell culture supernatants. Filtration studies indicated that the MW of this factor(s) is between 2,000 and 10,000 daltons. No such activity was detected in culture supernatants of unstimulated mononuclear cells. Production of the cytokine was blocked by cycloheximide, indicating that protein synthesis was necessary. This factor(s), by enhancing PMN degranulation, may augment PMN‐mediated tissue destruction in diseases such as RA.
Sudden quadriplegia complicating ossification of the posterior longitudinal ligament and diffuse idiopathic skeletal hyperostosis
Authors: Pouchot Jacques , Watts Craig S. , Esdaile John M. , Hill Ross O.
Published: February 2007

The association of ossification of the posterior longitudinal ligament (OPLL) and diffuse idiopathic skeletal hyperostosis (DISH) has been recently described. It may result in devastating compressive myelopathy. We report a case of quadriplegia complicating OPLL in a patient with DISH. In addition, we present a brief review of the literature on OPLL. This report illustrates the importance of appropriate neurologic and radiologic evaluation of persons with DISH, to help prevent severe neurologic complications.
Effects of psychological therapy on pain behavior of rheumatoid arthritis patients. treatment outcome and six‐month followup
Authors: Bradley Laurence A. , Young Larry D. , Anderson Karen O. , Turner Robert A. , Agudelo Carlos A. , Mcdaniel Lisa K. , Pisko Edward J. , Semble Elliott L. , Morgan Timothy M.
Published: February 2007

A randomized clinical trial was performed to evaluate a psychological treatment intervention and a social support program, compared with a control program in which no adjunct treatment was rendered, and their effects upon pain behavior, affect, and disease activity of 53 patients with rheumatoid arthritis. The psychological intervention produced significant reductions in patients' pain behavior and disease activity at posttreatment. Significant reductions were also observed in trait anxiety at posttreatment and 6‐month followup. Relaxation training may have been the most important component of the psychological intervention. The social support program produced a significant reduction in trait anxiety only at posttreatment. This is the first well‐controlled study to demonstrate reduced pain behavior, disease activity, and trait anxiety following psychological treatment.
The “chronic, active epstein‐barr virus infection” syndrome and primary fibromyalgia
Authors: Buchwald Dedra , Goldenberg Don L. , Sullivan John L. , Komaroff Anthony L.
Published: February 2007

Fifty patients with primary fibromyalgia who had been followed in an academic rheumatology practice frequently reported symptoms thought to be typical of “chronic Epstein‐Barr virus infection,” but not of fibromyalgia: recurrent sore throat (54%), recurrent rash (47%), chronic cough (40%), recurrent adenopathy (33%), and recurrent low‐grade fevers (28%). In 55% of the patients, illness had begun suddenly, with what seemed to be a viral syndrome. Antibody titers to Epstein‐Barr virus in the patients with fibromyalgia, however, were not significantly different from those in age‐ and sex‐matched “healthy” and “unhealthy” control subjects.
Arthritis in hereditary hemochromatosis
Authors: Mathews Jeffrey L. , Williams H. James
Published: February 2007

Seven pedigrees with 45 members were evaluated for arthropathy associated with hereditary hemochromatosis (HC). Patients with symptomatic extraarticular disease were compared with asymptomatic patients who had evidence of HC on laboratory findings, and with normal subjects. Patients who were homozygous for HC were compared with heterozygous patients and normal subjects. HC arthritis does not appear to be an early predictor of disease, and chondrocalcinosis is a late manifestation of HC arthropathy.
An unusual syndrome of a devastating noninflammatory vasculopathy associated with anticardiolipin antibodies: report of two cases
Authors: Ingram Shirley B. , Goodnight Jr. Scott H. , Bennett Robert M.
Published: February 2007

We describe 2 patients with marked elevations of anticardiolipin antibodies who developed multiple‐organ disease characterized by a noninflammatory vasculopathy. Their cases were remarkable for the fulminant nature of their thrombotic diathesis, which was heralded by a prominent livedo reticularis of the extremities. Both patients had a serologic profile and salivary gland biopsy findings that were consistent with a diagnosis of primary Sjögren's syndrome.
A comparison of changes seen on radiographs of rheumatoid arthritis patients in australia and in china
Authors: Moran Helen , Chen Shun‐Le , Muirden Kenneth D. , Jiang Shao‐Ji , Gu Yue‐Ying , Hopper John , Jiang Pei‐Lin , Lawler Gary , Bai Mark Xu Jung
Published: February 2007

To test the hypothesis that rheumatoid arthritis in patients in China is milder in severity than that in patients in a western country, a comparison was made of 2 series of consecutive outpatients with definite or classic rheumatoid arthritis who were attending referral centers in Melbourne, Australia and Shanghai, China. This paper reports the findings on radiographs of the wrists and hands. Making allowances for age and duration of disease, changes were more frequent and severe in the Australian patient series, particularly at the meta‐carpophalangeal joints.
Idiopathic periosteal hyperostosis with dysproteinemia (goldbloom's syndrome): case report and review of the literature
Authors: Cameron Bonnie J. , Laxer Ronald M. , Wilmot Dan M. , Greenberg Mark L. , Stein Leonard D.
Published: February 2007

Idiopathic subperiosteal new bone formation is uncommon in childhood. We report a case of diffuse periostitis in association with hypergammaglobulinemia and hypoalbuminemia in a 12‐year‐old boy. In 1966, 2 cases of idiopathic periosteal hyperostosis with accompanying dysproteinemia were documented. This report serves as a review of this unique and perplexing problem in clinical diagnosis.
Undiagnosed chronic monarthritis. clinical and evolutionary profile
Authors: Blocka Kenneth L. N. , Sibley John T.
Published: February 2007

The features and clinical course in 38 patients (25 women, 13 men) who had chronic monarthritis of undetermined origin (UCM) were surveyed over a mean followup period of 24.6 months. At the end of the study, the cause was still unknown in 26 patients (65.7%). In 10 patients, symptoms resolved spontaneously. In the remaining 12 patients, a diagnosis became apparent after a mean period of 17.2 months; diagnoses included spondylarthritis (6 patients), rheumatoid arthritis (3 patients), osteoarthritis (1 patient), erosive arthropathy (1 patient), and glomus tumor (1 patient). Patients in whom a diagnosis emerged were more likely to have positive findings on the following studies: rheumatoid factor (2 of 12); HLA—B27 typing (6 of 11); bone scan, positive over the sacroiliac joint or non‐index joint(s) (4 of 6); and roentgenograms of the sacroiliac joint (3 of 8). Findings of these same studies were notably negative in the subgroup of patients with UCM that spontaneously resolved.
One‐year experience in patients treated with auranofin following completion of a parallel, controlled trial comparing auranofin, gold sodium thiomalate, and placebo
Authors: James Williams H. , Dahl Stephen L. , Ward John R. , Karg Miki , Willkens Robert F. , Meenan Robert F. , Altz‐Smith Mary , Clegg Daniel O. , Mikkelsen William M. , Kay Donald R. , Weinstein Arthur , Guttadauria Maria , Paulus Harold E. , Kaplan Stanley B.
Published: February 2007

Following a 21‐week double‐blind trial that compared the effects of treatment with auranofin (AUR), gold sodium thiomalate, and placebo in 193 patients, 147 patients entered a 1‐year, open‐label study of treatment with AUR (6 mg/day). Results of this open‐label study suggest that AUR has a long‐term use profile similar to that of other slow‐acting antirheumatic drugs. AUR appears to be capable of sustaining an initial response to gold sodium thiomalate. The withdrawal rate remains relatively high: Nearly half of the study patients had discontinued AUR by the end of 1 year.
Natural course of joint destruction and fluctuation of serum c1q levels in patients with rheumatoid arthritis
Authors: Ochi Takahiro , Iwase Rokuro , Yonemasu Kunio , Matsukawa Mitsuhiro , Yoneda Minoru , Yukioka Masao , Ono Keiro
Published: February 2007

Using the number of joints with erosion in a total of 68 joints throughout the body, we studied a population of patients with rheumatoid arthritis whose disease duration was 10–15 years. Three groups, each showing a Poisson distribution, were found: the subset with least erosive disease (LES), the subset with more erosive disease (MES), and the subset with mutilating disease (MUD). The mean number of joints with erosion was 10.9 in LES, 32.2 in MES, and 53.5 in MUD. In LES, erosive articular changes were primarily limited to the peripheral smaller joints. In MES, the larger axial joints were also involved. Almost all joints were extensively damaged in MUD. During the early period of disease, differences between the 3 groups were highly significant in the rapidity of carpal bone destruction, as assessed by the yearly reduction of carpal height ratio (P < 0.001), and in the serum C1q level (P < 0.001).
Incidence of anti‐human ig with restricted specificity in japanese, kuwaiti, and swedish patients with rheumatoid arthritis
Authors: Grubb R. , Matsumoto H. , Sattar M. A.
Published: February 2007

Assuming that anti‐allotypic anti‐Ig in rheumatoid arthritis is stimulated by the individual's allotype, it would be reasonable to expect a higher incidence of anti‐G1m(a) in individuals carrying G1m(a). There is marked divergence among various populations in allotype frequencies. G1m(a) allotype and the prevalence of anti‐Ig reactive with G1m(a) Ig were determined in 18 Kuwaiti, 23 Japanese, and 41 Swedish rheumatoid arthritis patients. An inverse relationship was observed between the frequency distribution of allotype G1m(a) and anti‐allotype; thus, the stimulus for the anti‐allotype is not the patient's own allotype.
Characterization of the antigen reactive with anti‐scl‐70 antibodies and its application in an enzyme‐linked immunosorbent assay
Authors: Juarez C. , Vila J. L. , Gelpi C. , Agusti M. , Amengual M. J. , Martinez M. A. , Rodriguez J. L.
Published: February 2007

The characteristics of the Scl‐70 antigen (topoisomerase I) have been analyzed by means of autoantibodies. This antigen is a DNA‐binding protein, dissociable from DNA at 0.3M NaCl and bound to a fraction of DNA that is very sensitive to nucleases. The molecular weight of the antigen is 105,000 daltons, whether dissociation conditions are used or not. Using chicken erythrocytes, and taking advantage of the strong interaction of the antigen with hydroxyapatite, we have designed a simple and fast purification protocol that allows the determination of anti–topoisomerase I antibodies by enzyme‐linked immunosorbent assay.