bluuebunny/crossref_metadata_2025 huggingface dataset:
The binding of antihistone antibodies to crithidia luciliae kinetoplasts is growth cycle‐dependent
Authors: Deng Jau‐Shyong , Sontheimer Richard D. , Lipscomb Mary F. , Gilliam James N.
Published: February 2007

The Crithidia luciliae immunofluorescence (CLIF) assay is widely used to test for native DNA (nDNA) antibodies in the diagnosis and management of systemic lupus erythematosus. However, sera from patients with drug‐induced lupus erythematosus or rheumatoid arthritis, which should not contain nDNA antibodies, occasionally react with the CL kinetoplast. We examined 36 sera from patients with systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, and drug‐induced lupus erythematosus, who had positive CLIF tests. All 36 sera were also antinuclear antibody‐positive with homogeneous and/or peripheral staining patterns on mouse kidney substrates. After hydrochloric acid extraction of the CL smears to remove histone and other nuclear protein antiges, 14 of the 36 sera no longer produced a positive result on the CLIF test. Ten of these 14 sera again gave a positive CLIF result after the hydrochloric acid‐extracted Crithidia substrate had been reconstituted with purified histone. These studies demonstrated that kinetoplast binding was due to antihistone antibodies in at least 10 of 36 initially CLIF‐positive sera. Antihistone antibodies were then purified with a histone‐affinity column, and these purified antibodies were reactive with CL kinetoplasts. Thus, the CLIF test is not specific for nDNA antibodies. Additional studies using CL from different days of culture indicated that histone antigen expression in the CL kinetoplast was a function of the life cycle of this organism and is most readily detected 2 days after initiation of culture.
Arthroscopy in septic arthritis. Lidocaine‐ and iodine‐containing contrast media are bacteriostatic
Authors: Dory M. A. , Wautelet M. J.
Published: February 2007

Puncture of septic foci is usually performed to determine the responsible bacteria. If contrast medium is used instead of saline to rinse the lesion and to withdraw an adequate bacteriologic specimen, the opacification provides valuable information about the extent of the changes. Since lidocaine is usually used as a local anesthetic when patients undergo this procedure, we tested the in vitro antibacterial effects of lidocaine 1%, as well as those of 2 contrast media—meglumine amidotrizoate and metrizamide—on several bacteria. In particular, we looked at the influence of the concentration of inoculum used and the duration of contact before culture. The contrast media did not significantly affect bacterial growth when contact before culture did not exceed 3 hours. In contrast, lidocaine had a significant antibacterial effect, indicating that it should not enter into contact with the bacteriologic specimen.
Diagnosis‐related group regulations. Implications for the practicing rheumatologist
Authors: Weinberger Morris , Potts Marilyn K. , Brandt Kenneth D.
Published: February 2007

Data from our university hospital on the 2 most common rheumatologic diseases that require hospitalization indicate that total charges for patients admitted with rheumatoid arthritis or systemic lupus erythematosus break down as follows: room, board, and nursing, 55%; tests/procedures, 30%; drugs, 5%; physical and occupational therapy, 5%; and miscellaneous, 5%. Thus, shortening the length of stay would be the most effective mechanism to reduce total charges. We also found marked heterogeneity in the single diagnosis‐related group containing rheumatoid arthritis and systemic lupus erythematosus inpatients under 70 years old who had no comorbid conditions. Planners should be sensitive to this as prospective reimbursement is extended beyond Medicare patients.
Autoantibody specificities of immune complexes sequestered in articular cartilage of patients with rheumatoid arthritis and osteoarthritis
Authors: Jasin Hugo E.
Published: February 2007

To define autoantibody specificities of immune complexes sequestered in articular cartilage of patients with rheumatoid arthritis and osteoarthritis, extracts were obtained from articular cartilage specimens from 16 patients with rheumatoid arthritis, 11 patients with osteoarthritis, and 6 normal controls. Radioimmunoassays of the extracts revealed that rheumatoid cartilage contained 37 times more IgM and 14 times more IgG than did normal cartilage extracts. In addition, osteoarthritic cartilage contained 3 times more IgM and IgG than the normal tissues. IgM rheumatoid factor was found in 13 of 16 rheumatoid cartilage extracts but in none of 11 osteoarthritic or 6 normal control extracts. IgG rheumatoid factor was detected in 4 of 7 seropositive rheumatoid but in none of 5 osteoarthritic cartilage extracts. More than 60% of the rheumatoid cartilage extracts were positive for native and denatured collagen II antibodies. Surprisingly, 50% of the osteoarthritic specimens also contained significant titers of collagen antibodies. Similar results were obtained with osteoarthritic menisci extracts. These findings indicate that the immune complexes sequestered in rheumatoid cartilage contain autoantibodies that are probably synthesized locally by cells infiltrating the inflamed synovium. If immune complexes trapped in cartilage play an important role in cartilage damage, our findings would provide a possible pathogenic mechanism that explains the self‐perpetuating and chronic nature of cartilage degradation in rheumatoid arthritis and osteoarthritis.
Evidence for intravascular coagulation in systemic onset, but not polyarticular, juvenile rheumatoid arthritis
Authors: Scott J. Paul , Gerber Patricia , Maryjowski Mona C. , Pachman Lauren M.
Published: February 2007

After observing a child with systemic onset juvenile rheumatoid arthritis (S‐JRA) who developed purpura fulminans in association with disseminated intravascular coagulation, with subsequent gangrene and autoamputation, we undertook a prospective study of coagulation parameters in children with JRA. Ten consecutive children with S‐JRA, 10 children with rheumatoid factor‐negative, polyarticular juvenile rheumatoid arthritis (P‐JRA), and 10 age‐ and sex‐matched controls were studied. Routine coagulation screening tests were performed, as were tests for plasma fibrinopeptide A (a sensitive measure of intravascular thrombin generation), factor VIII‐related antigen (an endothelial cell protein), and platelet factor 4 (a plateletsecreted protein). Our studies suggest that activation of intravascular coagulation is common in systemic onset JRA, but not in rheumatoid factor‐negative, polyarticular disease. The coagulopathy may cause severe morbidity. In addition, marked elevations of plasma factor VIII‐related antigen suggest perturbation of endothelial cells and vascular involvement in S‐JRA, but not in P‐JRA. Normal ranges of platelet factor 4 indicate that intravascular platelet consumption does not occur in either type of JRA, despite the thrombocytosis common in both.
Patterns of antihistone antibody specificity in systemic rheumatic disease. I. Systemic lupus erythematosus, mixed connective tissue disease, primary sicca syndrome, and rheumatoid arthritis with vasculitis
Authors: Bernstein Robert M. , Hobbs Roderick N. , Lea Donald J. , Ward Donald J. , Hughes Graham R. V.
Published: February 2007

A new fluorimetric assay was used to measure the relative amounts of antibodies to individual nuclear histones in sera from 102 patients with systemic lupus erythematosus (SLE), mixed connective tissue disease, primary sicca syndrome, and rheumatoid arthritis with vasculitis. In SLE sera, the predominant responses were to histones H‐1, H‐2B, and H‐3, with marked elevations of binding to H‐1 and H‐2B in one‐third of the patients, and to H‐3 in one‐fourth; antibodies of both the IgG and IgM classes were also detected. In a few SLE sera, the pattern of histone response differed or was restricted to 1 immunoglobulin class. In mixed connective tissue disease, only 2 of 9 sera showed elevated histone binding activity, the response being predominantly to H‐3 in 1 patient and to H‐1 and H‐2B in the other. Binding to H‐2B was also prominent in 2 of 3 patients with primary sicca syndrome. The highest antihistone reactivity and the most heterogeneous response patterns were observed in patients who had rheumatoid arthritis with vasculitis; 6 of 8 of those sera had elevated histone reactivity. In SLE, the highest histone binding results were found among patients with a history of photosensitivity. Histones are closely associated with DNA in the nucleosome, and we speculate that antihistone antibodies could arise as a result of damage to DNA, induced by drugs or irradiation.
Quantitation of the sm nuclear antigen in tissues and activated lymphocytes
Authors: Boyer Cinda M. , Eisenberg Robert A. , Cohen Philip L.
Published: February 2007

Anti‐Sm antibodies are specific for the diagnosis of systemic lupus erythematosus both in humans and in mice. Because the autoantibody response to this nuclear ribonucleoprotein particle is probably antigen driven, we have quantitated the Sm antigen in cells and tissues, using a highly sensitive and specific enzyme‐linked immunosorbent assay. The Sm content of several in vitro cell lines was determined to be approximately 1 pg of Sm/cell. We found that murine spleen cells stimulated in vitro with either T cell or B cell mitogens contained up to 10 times more Sm than did unstimulated cells and that they also released increased amounts of Sm. In a survey of organs from several mouse strains, we found that lymphoid tissues had the largest amounts of Sm and that the Sm content of a particular tissue correlated with its DNA content. Increased amounts of Sm in and around activated lymphocytes, as found in systemic lupus erythematosus, may provide a source of antigen for the induction of the anti‐Sm autoantibody.
Assessing physician/patient perceptions in rheumatoid arthritis. A vital component in patient education
Authors: Silvers Ilene J. , Hovell Melbourne F. , Weisman Michael H. , Mueller Mary Rose
Published: February 2007

Patient education surveys were completed by 101 patients with rheumatoid arthritis and by 28 rheumatologists to assess and compare patients' reports with physicians' perceptions of patients' needs regarding content, provider, and education program delivery methods. Both groups agreed on the importance of patients' education about arthritis, especially on the topics of medication, physician/patient communication, quackery, and maintaining ambulation. A higher proportion of physicians reported that patient education was needed in psychosocial areas, activities of daily living, sexual concerns, and community resources. Patients sought more education in disease process, diagnostic procedures, and nutrition. Patients rated pharmacists and nutritionists significantly more important as educational sources than did physicians. Both groups reported individual patient/practitioner meetings as the preferred delivery method. Physicians reported group education to be valuable for some psychosocial topics; patients disagreed significantly. Despite considerable consensus, disagreements were evident in the psychosocial area and in the role of allied health professionals. Clarification, understanding, and resolution of these differences should be sought before implementing patient education programs.
The effect of glucocorticoids on bone mass in rheumatoid arthritis patients. Influence of menopausal state
Authors: Als Orla Skibsted , Gotfredsen Anders , Christiansen Claus
Published: February 2007

We studied 97 patients with definite or classic rheumatoid arthritis (RA). Fifty‐four patients (19 premenopausal women, 25 postmenopausal women, and 10 men) had been treated with low‐dose glucocorticoids for at least 12 months (mean dose <10 mg/day). The remaining 43 patients (15 premenopausal women, 17 postmenopausal women, and 11 men) had been treated with penicillamine, and served as a patient control group. The distal forearm bone mineral content (BMC) was measured in all patients by single photon absorptiometry using 125I, and the total body bone mineral (TBBM) was measured in 61 patients by dual photon absorptiometry using 153Gd. Compared with normal controls, both treatment groups had significantly decreased BMC and TBBM (0.01 < P < 0.001). When the patients were stratified according to pre‐ and postmenopausal state, we found significantly lower BMC and TBBM values in the premenopausal glucocorticoid‐treated women than in penicillamine‐treated women. However, no differences in BMC and TBBM values were found in the corresponding postmenopausal groups. In the premenopausal women treated with glucocorticoids, the duration of treatment and cumulative dose correlated with BMC. No such correlations were found in the postmenopausal women. We conclude that 1) RA is associated with loss of bone mass, 2) systemic glucocorticoid treatment further aggravates the bone loss, 3) in postmenopausal RA patients, the bone loss resulting from menopause and from the disease itself is not accelerated by low‐dose glucocorticoids, and 4) in premenopausal RA patients, however, the bone mass is significantly affected by glucocorticoid treatment. We therefore suggest that these factors be considered when prescribing glucocorticoids, in order to minimize the bone loss.
Cartilage response to mechanical force in high‐density chondrocyte cultures
Authors: Van Kampen G. P. J. , Veldhuijzen J. P. , Kuijer R. , Van de Stadt R. J. , Schipper C. A.
Published: February 2007

High‐density cultures of chick embryonic chondrocytes were exposed to intermittent compressive force (ICF) of physiologic magnitude for 24 hours. Proteoglycan synthesis was significantly increased in chondrocyte cultures exposed to ICF as compared with control cultures. Similar effects were found in explants of epiphyseal cartilage. Proteoglycans extracted with guanidine‐HCI from cultures exposed to ICF aggregated better with hyaluronic acid than did control cultures, as shown by Sepharose 2B gel chromatography. In addition, the amount of non‐extractable proteoglycans was increased in ICF cultures. We conclude that ICF not only increases the synthesis of proteoglycans but also improves the aggregating capacity of proteoglycans and the coherence of proteoglycans with other matrix components. High‐density cultures of epiphyseal chondrocytes provide a suitable model to study the processes involved in the perception of and the subsequent cellular response to compressive force by cartilage.
Induction of chronic polyarthritis in rabbits by hyperimmunization with Escherichia Coli. I. Pathologic and serologic features in two breeds of rabbits
Authors: Aoki Shigehisa , Ikuta Koji , Nonogaki Tsunemasa , Ito Yoshitake
Published: February 2007

Hyperimmunization of 147 rabbits (outbred Japanese white rabbits and New Zealand white [NZW] rabbits bred in a closed colony) with heat‐killed Escherichia coli 0:14 in Freund's incomplete adjuvant resulted in the animals developing a chronic polyarthritis resembling rheumatoid arthritis (RA). While both Japanese white and NZW rabbits showed a high incidence of the induced arthritis, a higher proportion of NZW rabbits developed the disease, suggesting that genetic influence is important in the development of RA‐like illness. This experimental model may be useful for the study of RA.
Comparative measurement efficiency and sensitivity of five health status instruments for arthritis research
Authors: Liang Matthew H. , Larson Martin G. , Cullen Karen E. , Schwartz Julie A.
Published: February 2007

Five health status instruments were administered in random order to 50 arthritis patients before and after total joint arthroplasty. Relative efficiency and sensitivity in measurement of change in pain, mobility and physical function, social role and social activity, and global health were assessed. The instruments had highly correlated scores, but had differences in certain dimensions. Inter‐instrument differentials were larger for social and global outcomes than for pain or mobility. No single instrument consistently outperformed the others. A method for determining relative efficiency is described.
Relationship between circulating interferon and anti‐interferon antibodies and impaired natural killer cell activity in systemic lupus erythematosus
Authors: Sibbitt Wilmer L. , Gibbs Dwayne L. , Kenny Carol , Bankhurst Arthur D. , Searles Robert P. , Ley Kenneth D.
Published: February 2007

Interferon (IFN) production and response are impaired in a high percentage of systemic lupus erythematosus (SLE) patients. In addition, elevated serum levels of α‐IFN or anti–α‐IFN antibodies are present in some SLE patients. This study examined the relationship of circulating IFN and anti‐IFN antibodies to the impairment of natural killer (NK) cell function in SLE. All 15 SLE patients studied had measurable circulating α‐IFN, while the normal controls had minimal serum IFN. Neither patient nor control sera contained any detectable anti–α‐IFN activity. However, most of the SLE patients demonstrated defects in NK cell function. Because these defects in NK cell function appeared to be associated with circulating IFN, but not anti‐IFN, antibodies, the effect of prolonged in vitro IFN exposure on NK cell function of peripheral blood mononuclear cells was determined. It was found that prolonged exposure to IFN induced both an apparent defect in IFN response and a definite impairment of baseline NK cell function. These results suggest that prolonged elevation of circulating α‐IFN levels could be responsible, in part, for the defects in natural cytotoxicity present in SLE.
Cartilage surface charge. A possible determinant in aging and osteoarthritic processes
Authors: Laver‐Rudich Zahava , Silbermann Michael
Published: February 2007

Polycationic labels such as cationized ferritin and colloidal iron were used to evaluate the surface negative charges over the mandibular condyles of ICR mice. The effects of neuraminidase, hyaluronidase, pronase, and collagenase on the binding of cationized ferritin and colloidal iron particles to the condylar articular surface were also studied. The results of this study clearly indicate that the surface area of the cartilaginous condyle is negatively charged and that its composition consists mainly of a collagenous material embedded within a proteinaceous matrix. With age, a substantial decrease in the density of negative charges took place along the surface area and, in particular, in the context of sialic acid residues. It is, therefore, possible that the reduction in cartilage surface charge might be associated with the onset of osteoarthritic changes commonly seen in aging humans and experimental animals.
Comparison of low‐dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A Controlled Clinical Trial
Authors: Williams H. James , Willkens Robert F. , Samuelson Cecil O. , Alarcón Graciela S. , Guttadauria Maria , Yarboro Cheryl , Polisson Richard P. , Weiner Steven R. , Luggen Michael E. , Billingsley Lynn M. , Dahl Stephen L. , Egger Marlene J. , Reading James C. , Ward John R.
Published: February 2007

One hundred eighty‐nine patients with rheumatoid arthritis were entered into a prospective, controlled, double‐blind multicenter trial comparing placebo and methotrexate (MTX). One hundred ten patients completed 18 weeks of therapy. No remissions were seen, but patients able to tolerate low‐dose pulse MTX therapy were significantly improved, compared with patients receiving placebo therapy, for all clinical variables measured, including joint pain/tenderness and swelling counts, rheumatoid nodules, and patient and physician assessment of disease activity. MTX treatment demonstrated statistically significant improvement over placebo in patients with anemia, elevated erythrocyte sedimentation rate, and rheumatoid factor. However, nearly one‐third of the patients receiving MTX were withdrawn for adverse drug reactions, of which elevated levels of liver enzymes was the most common. Pancytopenia occurred in 2 patients taking MTX. All adverse drug effects resolved without sequelae. MTX appears to be effective in the treatment of active rheumatoid arthritis but requires close monitoring for toxicity.
Pulmonary involvement in systemic sclerosis (scleroderma)
Authors: Steen Virginia D. , Owens Gregory R. , Fino Gregory J. , Rodnan Gerald P. , Medsger Thomas A.
Published: February 2007

One hundred sixty‐five nonsmoking systemic sclerosis patients were evaluated by pulmonary function testing. Restrictive lung disease and an isolated reduction of the diffusing capacity of carbon monoxide were the most frequent abnormalities. Patients with the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias) had a similar frequency and severity of pulmonary involvement compared with the patients who had diffuse scleroderma. CREST syndrome patients with restrictive lung disease rarely had the anticentromere antibody and had more skin and joint involvement of their hands, compared with other CREST syndrome patients. Dyspnea and rales were most commonly found in patients with restrictive lung disease. Fibrosis, shown on chest radiograph, and pulmonary function abnormalities correlated poorly with each other. Dyspnea was associated with restrictive disease, and rales were more commonly found in patients with fibrosis. Patients with a restrictive abnormality had the worst prognosis, with a 5‐year survival rate of 58%, although death from pulmonary causes was uncommon. Comparison of these nonsmoking patients with 137 scleroderma patients who smoked, seen during the same time period, revealed more frequent and severe obstructive changes in smokers. Smoking patients with restrictive lung disease had more severe disease than nonsmoking patients. The single breath diffusing capacity for carbon monoxide was significantly decreased in the patients who smoked compared with the nonsmokers. These data confirm that pulmonary function abnormalities are common in patients with systemic sclerosis including CREST syndrome. Smoking appears to have an additive deleterious effect on pulmonary function and should be strongly discouraged.
Angiographic findings in mixed connective tissue disease. Correlation with fingernail capillary photomicroscopy and digital photoplethysmography findings
Authors: Peller Jeffrey S. , Gabor Gary T. , Porter John M. , Bennett Robert M.
Published: February 2007

Thirteen patients with mixed connective tissue disease underwent hand angiography to assess the degree of vascular abnormalities and their correlation to nailfold capillary microscopy and digital photoplethysmography findings. Organic obstruction was found in 60% of ulnar arteries, 87% of superficial arches, 13% of deep arches, and 65% of digital arteries. Fingernail capillary abnormalities were seen in 90% of patients. Normal photoplethysmography results had a predictive value of 91% for identifying digits without bilateral occlusions. These findings indicate a hitherto unrecognized propensity for disease of both small and medium‐sized vessels in patients with mixed connective tissue disease.
The association between Mi‐2 antibodies and dermatomyositis
Authors: Targoff Ira N. , Reichlin Morris
Published: February 2007

Antibodies to Mi, an antigen in calf thymus extract, have been demonstrated by complement fixation inhibition in polymyositis (PM) and dermatomyositis (DM) sera but not in the sera of individuals without myositis. The original Mi reference serum defined 2 precipitating antibodies, using immunodiffusion (ID). Anti‐Mi‐1 was not active in complement fixation. We have now studied in further detail anti‐Mi‐2, which appears to be the antibody in Mi serum that fixes complement. Mi‐2 antigen was purified by immunoaffinity chromotography. An enzyme‐linked immunosorbent assay (ELISA) to measure Mi‐2 antibody, using this antigen, was used to test the sera of 139 myositis patients: 52 had DM and 87 had PM. Control sera from 35 normal subjects and 93 patients with other connective tissue diseases were also tested. Only 13 sera were considered definitely positive for anti‐Mi‐2. All were from patients who had myositis, 11 of whom had DM. Only DM sera had anti‐Mi‐2 by ID, and all sera with anti‐Mi‐2 by ID were positive by ELISA. A number of other sera, including many from patients with other connective tissue diseases and 2 from normal subjects (all without precipitating antibodies) had lower elevations which were of uncertain significance. Detection of anti‐Mi‐2 by ID as well as by ELISA was significantly more frequent in DM than in PM. Anti‐Mi‐2 appears to be closely linked to DM, and is the first specific serologic marker for this form of myositis.
Release of interleukin‐1 from human synovial tissue in vitro
Authors: Wood David D. , Ihrie Earl J. , Hamerman David
Published: February 2007

During the enzymatic disaggregation of human synovium, used in the process of isolating synoviocytes, a factor was liberated into the culture medium that exhibited the thymocyte mitogenic properties of interleukin‐1. Like interleukin‐1, this synovial‐derived mitogen could be isolated using an affinity column of antihuman leukocytic pyrogen. By gel filtration and isoelectric focusing, the mitogen cofractionated with human monocyte‐derived interleukin‐1. Finally, the isolated mitogen was shown to exhibit other properties of interleukin‐1: stimulation of the secretion of interleukin‐2, enhancement of the titer of acute‐phase proteins in vivo, and stimulation of the release of prostaglandin E2 from human synoviocyte cultures. These observations suggest that interleukin‐1 can be derived from the human synovium.
Different populations of rheumatoid adherent cells mediate activation versus suppression of t lymphocyte proliferation
Authors: Klareskog Lars , Holmdahl Rikard , Rubin Kristofer , Victorin Åse , Lindgren Jan Åke
Published: February 2007

Adherent cells from synovial tissue of rheumatoid arthritis patients were fractionated on Percoll density gradients and analyzed to determine phenotypes, effects on allogeneic T lymphocyte proliferation, and production of prostaglandin E2 (PGE2). Cells expressing HLA‐DR predominated in all fractions, and esterasepositive cells were enriched in light fractions. Heavy cells were potent stimulators in the mixed lymphocyte reaction and produced little PGE2, whereas light cells suppressed the mixed lymphocyte reaction and produced a large quantity of PGE2. These results suggest that macrophage‐like synovial cells that suppress T helper lymphocyte activity are generated secondary to synovial lymphocyte activation in rheumatoid arthritis.
Suppression of rheumatoid factor synthesis by antiidiotypic antibody in rheumatoid arthritis patients with cross‐reactive idiotypes
Authors: Takeuchi Tsutomu , Hosono Osamu , Koide Jun , Homma Mitsuo , Abe Tohru
Published: February 2007

The effect of antiidiotypic antibody on the in vitro production of rheumatoid factor was studied in rheumatoid arthritis patients with cross‐reactive idiotypic determinants. Antiidiotypic antibodies (ascites IgG) were developed against monoclonal rheumatoid factor (Ka m‐RF) by a cell fusion procedure. These antibodies were idiotype‐specific, since: 1) they reacted only with F(ab')2 fragment of Ka m‐RF; 2) they failed to react with normal IgM without rheumatoid factor activity; and 3) their F(ab')2 fragment inhibited the rheumatoid factor activity of Ka m‐RF. The antiidiotypic antibody strongly suppressed the in vitro production of rheumatoid factor by lymphocytes from unrelated rheumatoid arthritis patients with cross‐reactive idiotypes. The suppression was specific, since ascites IgG failed to suppress in vitro anti‐keyhole limpet hemocyanin antibody production by the lymphocytes. These results indicate that antiidiotypic antibody may influence the regulation of rheumatoid factor production in patients with rheumatoid arthritis.
In vitro production and scavenging of hydrogen peroxide by D‐penicillamine. Relationship to copper availability
Authors: Staite Nigel D. , Messner Ronald P. , Zoschke David C.
Published: February 2007

The capacity of D‐penicillamine (DP) to produce or scavenge hydrogen peroxide was investigated. DP added to copper produced H2O2. Greater production was observed with copper sulfate than with copper bound to ceruloplasmin. In contrast, DP in the absence of copper scavenged H2O2, as measured in a direct assay. Furthermore, DP or D‐cysteine alone reversed H2O2‐mediated inhibition of concanavalin A‐stimulated mononuclear cell proliferation. These opposing immunomodulating properties of DP may be relevant to its toxic or therapeutic actions in rheumatoid arthritis.
Detection of cross‐reactive anti‐DNA antibody idiotypes in the serum of systemic lupus erythematosus patients and of their relatives
Authors: Isenberg D. A. , Shoenfeld Y. , Walport M. , Mackworth‐Young C. , Dudeney C. , Todd‐Pokropek A. , Brill S. , Weinberger A. , Pinkas J.
Published: February 2007

Two common cross‐reacting anti‐DNA antibody idiotypes designated 16/6 and 32/15, previously identified in the serum of patients who have systemic lupus erythematosus, were found in 24% and 7%, respectively, of 147 first‐degree relatives. These findings imply that high‐frequency germ‐line genes exist among lupus relatives, as well as patients. These dominant or public anti‐DNA antibody idiotypes are not likely to be pathogenic factors, but are probably a genetically associated phenomenon.
Impaired b cell proliferation by Staphylococcus aureus Cowan 1 in patients with systemic lupus erythematosus
Authors: Sawada Shigemasa , Amaki Satoshi , Takei Masami , Karasaki Miki , Amaki Ichita
Published: February 2007

We examined the proliferative response to Staphylococcus aureus Cowan 1 (SAC) by enriched peripheral blood B cells from patients with systemic lupus erythematosus (SLE). Responses of B cells from patients with active and inactive SLE were significantly lower than those of B cells from normal individuals. Hyporesponsiveness to SAC was not observed in healthy family members of SLE patients. This hyporesponsiveness did not correlate with prednisolone therapy and could not be attributed to serum factors; it did correlate with the presence of suppressor monocytes. However, we could not exclude the possibility of enhanced sensitivity of SLE B lymphocytes to suppressive signals delivered by the monocytes.
Synthesis, secretion, and deposition of fibronectin in cultured human synovium
Authors: Lavietes Beverly B. , Carsons Steven , Diamond Herbert S. , Laskin Richard S.
Published: February 2007

We examined fibronectin synthesis, secretion, and deposition in vitro by primary explants of rheumatoid synovium. Primary cultures initiated from tissue with monocytic infiltrates had higher levels of fibronectin synthesis; addition of dexamethasone at concentrations known to stimulate other tissue fibroblasts increased fibronectin synthesis and secretion. Newly synthesized fibronectin recovered from primary rheumatoid culture medium had a higher apparent molecular weight (240‐245 kd), on sodium dodecyl sulfate‐polyacrylamide gel electrophoresis, compared with fibronectin recovered from passaged normal and rheumatoid cultures (230 kd). Primary rheumatoid explant cultures had a characteristic morphology which correlated with fibronectin deposition. Dense deposits of fibronectin extracellular matrix covered overlapping synoviocytes adjacent to esterase‐positive mononuclear cells. Dexamethasone‐treated cultures showed little fibronectin deposited as extracellular matrix and did not develop overlapping cellular networks. Characteristic patterns of fibronectin synthesis and deposition in primary rheumatoid cultures appear to result from interaction between fibroblastic and monocytic cells. This culture system may provide a model by which to study interactions between cells and extracellular matrix components that regulate synovial cell function.
Low synovial clearance of iodide provides evidence of hypoperfusion in chronic rheumatoid synovitis
Authors: Wallis Wayne J. , Simkin Peter A. , Nelp Wil B.
Published: February 2007

Iodide clearance was measured in the chronic knee effusions of 11 patients with rheumatoid arthritis and 9 patients with osteoarthritis. The mean (±SE) iodide clearance of 1.92 ± 0.30 ml/minute in rheumatoid arthritis effusions did not differ significantly from the 2.19 ± 0.52 ml/minute found in osteoarthritis effusions. Clearance values in rheumatoid arthritis patients ranged widely (0.79–3.22 ml/minute). Iodide clearance in these patients correlated directly with synovial fluid (SF) pH (r = 0.731, P = 0.005), SF glucose: serum glucose ratio (r = 0.746, P = 0.004), and SF temperature (r = 0.878, P = 0.001), and indirectly with SF lactate (r = −0.782, P = 0.002) and percentage of SF neutrophils (r = −0.581, P = 0.03). These relationships support the hypothesis that rheumatoid synovitis is often marked by tissue hypoperfusion, and that the “sickest” rheumatoid joints (as defined by physiologic indices) are the most ischemic.
Extracellular matrix‐cytoskeletal interactions in rheumatoid arthritis. I. Immunoelectron microscopic analysis of the fibronexus at the adhesive surface of normal porcine type B synoviocytes in vitro
Authors: Singer Irwin I. , Kazazis Diana M. , Kawka Douglas W. , Rupp Elizabeth A. , Bayne Ellen K.
Published: February 2007

We studied cell surface interactions between the fibronectin (FN)‐containing extracellular matrix and the actin cytoskeleton of normal porcine synoviocytes in vitro, using electron microscopic methods. These type B synovial cells were distinguishable from dermal fibroblasts co‐isolated from the same organism, because of their very long cellular processes and their ability to synthesize prostaglandin E2 after stimulation with interleukin‐1. With plastic sections, we found end‐to‐end (tandem) and track‐like (lateral) transmembrane associations of extracellular fibers and cortical 5‐nm microfilaments localized along the attenuated synoviocyte processes in postconfluent cultures. Very similar FN–actin complexes, termed fibronexus (FNX), have been observed on cultured fibroblasts and on granulation tissue myofibroblasts in vivo. Using double‐label immunoelectron microscopy with monospecific antibodies applied to ultrathin frozen sections of synoviocytes cut in situ, we proved that these FNX were indeed composed of associated FN and actin filaments. The striking finding of numerous FNX in cultured type B synoviocytes strongly suggests that the FNX is a major cell surface adhesion site in normal synovium, which may play an important role in pannus formation, connective tissue remodeling, and synoviocyte proliferation in patients with rheumatoid arthritis.
Determination of 16 alpha‐hydroxyestrone by radioimmunoassay in systemic lupus erythematosus
Authors: Lahita Robert G. , Bucala Richard , Bradlow H. Leon , Fishman Jack
Published: February 2007

A radioimmunoassay for the feminizing metabolite 16 alpha–hydroxyestrone was applied to a variety of sera from healthy volunteers, patients with active or inactive systemic lupus erythematosus (SLE), and patients with other rheumatic diseases. A significant increase in this metabolite was detected in patients with SLE, especially those with active disease, compared with normal controls (P < 0.001). SLE patients were categorized as having either active or inactive disease by clinical and laboratory criteria. Many patients who had clinically and serologically active disease were found to have normal levels of this estrogenic metabolite, and several explanations for these differences are explored in this report. Despite a poor correlation of hormone levels with age, antibody levels, or complement levels in patients with SLE, those patients with the highest levels of hormone were among those whose disease was clinically most active.
Two histopathologic types of inflammatory vascular disease in MRL/Mp autoimmune mice. Model for human vasculitis in connective tissue disease
Authors: Alexander Elaine L. , Mover Carolyn , Travlos Gregory S. , Roths John B. , Murphy Edwin D.
Published: February 2007

We have recently described 2 histopathologic types of inflammatory vascular disease (IVD) in patients with Sjögren's syndrome (SS): neutrophilic IVD (NIVD) and mononuclear IVD (MIVD). Autoimmune MRL/Mp mice, which have many features of SS, spontaneously develop IVD which is histopathologically indistinguishable from that observed in human SS patients. Both MRL/Mp−+/+ and MRL/Mp‐lpr/lpr mice develop MIVD which evolves into NIVD and results in decreased survival; the transition to NIVD is accelerated by the lpr gene. The presence of the lpr gene on other genetic backgrounds does not result in a similar acceleration of IVD and associated decreased survival. Thus, the spontaneous autosomal recessive mutation lpr appears to modulate the development of IVD in a strain of mice with an underlying propensity for vasculitis. Based on our observations on IVD in SS patients and MRL/Mp mice, we propose a new model which may enhance our understanding of the immunopathogenesis of IVD in connective tissue disease.
Referral of musculoskeletal disease patients by family and general practitioners
Authors: Felson David T. , Meenan Robert F. , Dayno Susan J. , Gertman Paul
Published: February 2007

We surveyed general and family practitioners to evaluate their patterns of referring musculoskeletal disease patients to rheumatologists and orthopedists. Patients who had rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis were most often referred to rheumatologists, whereas patients with osteoarthritis, persistent low back pain, and post‐traumatic knee pain were most often referred to orthopedists. As conditions worsened in severity, referrals were more frequent. Patients with conditions that were difficult to diagnose, such as possible shoulder tendinitis that was unresponsive to initial nonsteroidal therapy, undiagnosed polyarthritis, and intermittent knee swelling with pain, were most often treated without referral and, when referred, were most often sent to orthopedists. Belief in the effectiveness of rheumatologists or orthopedists correlated strongly with reported referral behavior, yet most respondents considered themselves capable of managing the majority of patients with musculoskeletal diseases. Neither practice arrangement, board certification, nor educational background affected referral behavior. However, younger physicians were more likely (P = 0.002) to refer patients to rheumatologists. Multivariate analysis showed that the significant predictors of global referral behavior were belief in the effectiveness of subspecialists and a small number of musculoskeletal problems seen by the generalist. The predictors of referral to rheumatologists were belief in rheumatologist efficacy and young physician age.
Hormonal modulation in systemic lupus erythematosus. Preliminary clinical and hormonal results with cyproterone acetate
Authors: Jungers Paul , Kuttenn Frédérique , Liote Frédéric , Pelissier Clara , Athea Nicole , Laurent Marie‐Christine , Viriot Joëlle , Dougados Maxime , Bach Jean‐François
Published: February 2007

We prospectively studied the effects of hormonal modulation using the antigonadotropic drug, cyproterone acetate (CA), in 7 female patients who had moderately active systemic lupus erythematosus. CA was taken orally at a mean daily dose of 50 mg for 21–33 months by 6 patients (9 months by the seventh patient) without any side effects. The number of clinical lupus exacerbations during CA treatment was lower than that during the corresponding pretreatment period (15 of 170 patient‐months versus 27 of 156 patient‐months P < 0.05), despite a reduction in the daily maintenance dose of corticosteroids or antimalarial drugs. Mean plasma testosterone levels were low initially and remained unchanged (0.66 ± 0.31 to 0.59 ± 0.23 nmoles/ liter), whereas plasma estradiol decreased markedly (from 0.6 ± 0 38 to 0.11 ± 0.03 nmoles/liter), resulting in a significant reduction in the estradiol:testosterone ratio (from 1.19 ± 0.68 to 0.23 ± 0.12) and in the plasma concentration of the sex hormone–binding protein. Thus, cyproterone acetate induced improvement in clinical lupus activity in parallel with the expected lower estradiol:testosterone balance.
Two types of inflammatory vascular disease in Sjögren's syndrome. Differential association with seroreactivity to rheumatoid factor and antibodies to Ro (SS‐A) and with hypocomplementemia
Authors: Molina Rodolfo , Provost Thomas T. , Alexander Elaine L.
Published: February 2007

Two types of inflammatory vascular disease (IVD) occur in Sjögren's syndrome: neutrophilic IVD (NIVD) and mononuclear IVD (MIVD). In 45 patients with Sjögren's syndrome, we examined the 2 types of IVD with respect to serologic associations. NIVD, unlike MIVD, was significantly associated with seroreactivity reflected by hyperglobulinemia (P = 0.01), rheumatoid factor (P = 0.002), antinuclear antibodies (P = 0.02), and antibodies to Ro (SS‐A) (P = 0.00006), and with hypocomplementemia (P = 0.03). The differential association of the 2 types of IVD with serologic reactivity and hypocomplementemia suggests that there may be basic differences in the immunopathogenesis of these 2 forms of IVD in Sjögren's syndrome.
Triamcinolone hexacetonide protects against fibrillation and osteophyte formation following chemically induced articular cartilage damage
Authors: Williams James M. , Brandt Kenneth D.
Published: February 2007

Although corticosteroids have been shown to cause articular cartilage degeneration, recent studies of experimentally induced osteoarthritis indicate that under certain conditions they may protect against cartilage damage and osteophyte formation. The present study examines the in vivo effect of triamcinolone hexacetonide on the degeneration of articular cartilage which occurs following intraarticular injection of sodium iodoacetate. Three weeks after a single injection of iodoacetate into the knees of guinea pigs, ipsilateral femoral condylar cartilage exhibited fibrillation, loss of staining with Safranin O, depletion of chondrocytes, and prominent osteophytes. In striking contrast, when triamcinolone hexacetonide was injected into the ipsilateral knee 24 hours after the intraarticular injection of iodoacetate, fibrillation was noted in only 1 of 6 samples, osteophytes were much less prominent, pericellular staining with Safranin O persisted, and cell loss was less extensive. Knees of animals which received only one‐tenth as much intraarticular triamcinolone hexacetonide after the iodoacetate injection also exhibited marked reduction in size and extent of osteophytes. However, the degree of fibrillation, loss of Safranin O staining, and chondrocyte depletion was similar to that observed in animals injected with iodoacetate but not treated with intraarticular steroid. No apparent morphologic or histochemical changes were observed after intraarticular injection of the steroid preparation alone. Thus, triamcinolone hexacetonide produced a marked, dose‐dependent protective effect in this model of chemically induced articular cartilage damage.
Quantification of keratan sulfate in blood as a marker of cartilage catabolism
Authors: Thonar Eugene J‐ M. A. , Lenz Mary Ellen , Klintworth Gordon K. , Caterson Bruce , Pachman Lauren M. , Glickman Paul , Katz Robert , Huff John , Kuettner Klaus E.
Published: February 2007

We have developed an enzyme‐linked immunosorbent‐inhibition assay which makes use of a monoclonal antibody specific for keratan sulfate to quantify keratan sulfate present as single chains in adult human serum. In adults hospitalized with conditions not thought to affect the turnover of keratan sulfate‐containing tissues, the serum levels varied from individual to individual (53–1,009 ng/ml) but did not show significant differences with respect to age, sex, or disease category. There were no significant differences between the serum levels of adult hospitalized patients and those of nonhospitalized normal adults. In contrast, the concentration of keratan sulfate in the sera of children aged 5–12 was significantly higher. No keratan sulfate was detected in the sera of 3 adult patients with macular corneal dystrophy, an inherited disorder of the cornea. This may indicate that individuals with macular corneal dystrophy have no keratan sulfate‐containing proteoglycans in their cartilage. Adult patients with osteoarthritis have significantly higher concentrations of circulating keratan sulfate. This suggests that the assay could prove valuable in monitoring increased cartilage catabolism in joint diseases.
Cartilage degradation by neutral proteoglycanases in experimental osteoarthritis. Suppression by steroids
Authors: Pelletier Jean‐Pierre , Martel‐Pelletier Johanne
Published: February 2007

In this study, we sought to determine the role of neutral proteases in cartilage matrix proteoglycan degradation, which occurs during the early stages of experimental osteoarthritis. The anterior cruciate ligament was transected in the right knees of 33 dogs. Their left knees served as sham operated controls. The animals were killed 2, 4, 8, and 12 weeks after surgery. Six dogs were treated with oral prednisone and then killed 4 weeks after surgery. Cartilage specimens from medial and lateral tibial plateaus were analyzed for DNA, proteoglycan content, and neutral proteoglycan degrading activity. No significant differences in cartilage DNA and proteoglycan content were observed among the dogs that had surgery, the controls, and the prednisonetreated animals. Total neutral metalloproteoglycan–degrading enzyme (NMPE) activity, determined by direct tissue assay, was significantly higher at all time points in osteoarthritic cartilage than in control cartilage. The active form of NMPE was significantly higher in osteoarthritic cartilage than in control cartilage at 2, 4, and 8 weeks in lateral plateaus and at 2 and 4 weeks in medial plateaus. Treatment for 4 weeks with prednisone (0.20–0.25 mg/kg/day) blocked the increased NMPE activity in osteoarthritic cartilage. The increase in the total and active neutral proteoglycanases supports the hypothesis that these enzymes are involved in early osteoarthritis. The synthesis of NMPE appears to be controlled by stimulating factors released by the synovium.
Reactivation of streptococcal cell wall‐induced arthritis by homologous and heterologous cell wall polymers
Authors: Esser Ronald E. , Stimpson Stephen A. , Cromartie William J. , Schwab John H.
Published: February 2007

Joint inflammation initially induced by intraarticular injection of an aqueous suspension of peptidoglycan‐polysaccharide (PG‐PS) fragments isolated from Streptococcus pyogenes was reactivated by systemic injection of a normally subarthropathic dose of homologous or heterologous cell wall polymers, including muramyl dipeptide and lipopolysaccharide. Reactivation was not correlated with the severity of the initial inflammatory reaction. Results of studies utilizing 125I‐labeled PG‐PS fragments suggested that reactivation was associated with increased localization of PG‐PS fragments in the joint following reinjection. These results indicate that the initial injury of the joint by S pyogenes PG‐PS fragments increases the susceptibility of the joint to subsequent injury. Furthermore, once the inflammatory reaction is initiated, it can be perpetuated by a variety of ubiquitous cell wall polymers derived from normal flora as well as from pathogenic bacteria.