bluuebunny/crossref_metadata_2025 huggingface dataset:
Interleukin‐1 activates phospholipase a2 IN HUMAN SYNOVIAL CELLS
Authors: Gilman Steven C. , Chang Joseph , Zeigler Pamela R. , Uhl Joanne , Mochan Eugene
Published: February 2007

Interleukin‐1 (IL‐1) treatment of synovial cells from rheumatoid arthritis and osteoarthritis patients resulted in a dose‐dependent secretion of phospholipase A2 (PLA2). IL‐1 also stimulated prostaglandin E2 and plasminogen activator synthesis, in parallel with PLA2 activation; all 3 were detectable within 6 hours of IL‐1 treatment and peaked by 24 hours. Synovial cell PLA2 required calcium (5 mM) and a neutral pH (7.5) for maximal activity and appears similar to the PLA2 in synovial fluid, which has been described previously. We conclude that PLA2 can be induced by IL‐1, and its secretion may contribute significantly to the inflammatory actions of IL‐1.
Clinical correlations and prognosis based on serum autoantibodies in patients with systemic sclerosis
Authors: Steen Virginia D. , Powell Donald L. , Medsger Thomas A.
Published: February 2007

Of 397 systemic sclerosis (scleroderma) patients from the University of Pittsburgh, who had serum determinations of both anti–Scl‐70 and anticentromere antibody (ACA), 26% had anti‐Scl‐70 and 22% had ACA. No patient had both autoantibodies. Weak associations with HLA–DR5 and HLA‐DR1 were detected with anti‐Scl‐70 and ACA, respectively. ACA was found almost exclusively (96%) in patients with limited cutaneous scleroderma (the CREST syndrome variant), but the majority (57%) of patients with limited scleroderma did not have this antibody. Among patients with limited scleroderma, those with ACA more often had calcinosis and telangiectasias and less often had pulmonary interstitial fibrosis and restrictive lung disease. However, the frequency of pulmonary hypertension and the survival rates were similar in the ACA + and ACA‐ limited scleroderma patients. Two‐thirds of patients with anti‐Scl‐70 had diffuse scleroderma, but only 33% of all diffuse scleroderma patients had this antibody. Within the subset of diffuse scleroderma, anti‐Scl‐70 was associated with peripheral vascular disease (digital pitting scars) and pulmonary interstitial fibrosis, but was not predictive of cardiac or renal involvement or survival. ACA and anti–Scl‐70 are useful in diagnosing and classifying systemic sclerosis variants and in predicting the natural course of the disease. Their mutually exclusive occurrence suggests either 2 separate clinical entities or important host factors determining their production.
Evidence that a humoral immune response to autologous cartilage proteoglycan can participate in the induction of cartilage pathology
Authors: Kresina Thomas F. , Yoo Jung U. , Goldberg Victor M.
Published: February 2007

We examined antiproteoglycan antibodies as an autoimmune response for induction of synovitis. This hypothesis was studied by monitoring humoral antiproteoglycan antibody following IgG induction of experimental immune synovitis, localization in the articular cartilage of an autologous immune response, and loss of proteoglycan from cartilage following intravenous administration of antiproteoglycan monoclonal antibodies. The data support the hypothesis that autoimmunity to cartilage macromolecules may play a role in the etiopathogenesis of arthritis.
Arthritis in patients with psoriasis is associated with an immunoglobulin gene polymorphism
Authors: Sakkas L. I. , Demaine A. G. , Panayi G. S. , Welsh K. I.
Published: February 2007

Using a DNA probe for the switch region of immunoglobulin heavy chain genes, together with the restriction endonuclease Sst I, we detected a particular polymorphic DNA pattern in 17 of 28 patients (60.7%) with psoriatic arthropathy but in only 5 of 41 patients (12.2%) with psoriasis alone. Our findings suggest that genes in the immunoglobulin region confer susceptibility to the development of arthropathy in patients with psoriasis.
Clostridial septic arthritis: case report and review of the literature
Authors: Fauser Douglas J. , Zuckerman Joseph D.
Published: February 2007

We describe a patient who had septic arthritis caused by Clostridium perfringens. Clostridial organisms are very uncommon causes of septic arthritis. Only 13 cases have been reported previously. The diagnosis should be suspected in patients with a history of penetrating joint trauma and in immunocompromised patients. Successful treatment has usually consisted of surgical synovectomy in combination with high‐dose intravenous penicillin therapy. Multiple aspirations of affected joints as a definitive treatment should be used with caution and only in patients who are not candidates for surgery.
The importance of age, education, and comorbidity in the substantial earnings losses of individuals with symmetric polyarthritis
Authors: Mitchell Jean M. , Burkhauser Richard V. , Pincus Theodore
Published: February 2007

A population‐based survey designed to be representative of the entire US population of working age (18–64 years) includes data on pain and swelling of specific joints in each subject. We analyzed these data to estimate work status and disability status, as well as earnings losses, associated with Symmetric Polyarthritis. Subjects identified in the survey as having Symmetric Polyarthritis were similar in age, race, sex, and marital status to rheumatoid arthritis patients seen in clinical settings. Overall, 51% of women with Symmetric Polyarthritis and 47% of men with Symmetric Polyarthritis were severely disabled, compared with 4.5% of women and 3.7% of men with no arthritis. Earnings of women and men with Symmetric Polyarthritis were only 27% and 48%, respectively, of earnings of individuals without arthritis. The total earnings gap between the 2 groups was 17.6 billion (1986 dollars). Econometric regression analyses indicated that about one‐third of this earnings gap was explained by the presence of Symmetric Polyarthritis. The remaining two‐thirds was explained by differences in age, education, and comorbidity between individuals with Symmetric Polyarthritis and those without arthritis. The earnings of individuals with Symmetric Polyarthritis, therefore, would be expected to be considerably lower than those of the general population, even if these individuals were not affected by arthritis. Nonetheless, earnings losses of at least 6.5 billion annually are explained by Symmetric Polyarthritis.
Dna sequence and conformation specificity of lupus autoantibodies. preferential binding to the left‐handed z‐dna form of synthetic polynucleotides
Authors: Thomas T. J. , Meryhew Nancy L. , Messner Ronald P.
Published: February 2007

The binding specificity of 16 sera from systemic lupus erythematosus (SLE) patients was studied by enzyme‐linked immunosorbent assay (ELISA), using 4 native DNAs of different guanine‐cytosine (G‐C) content and a group of synthetic polynucleotides. All the SLE sera showed increased binding to poly(dA‐dC)‐poly(dG‐dT), compared with calf thymus DNA in the right‐handed B conformation. No significant differences were noted in binding of selected SLE sera to the native DNAs that differed in G‐C content or superhelicity of DNA. With poly(dG‐dC).poly(dG‐dC) and poly(dG‐m5dC).poly(dG‐m5dC), the majority of SLE sera showed a preferential binding to the salt‐induced Z form, compared with the B form. In addition, an average twelve‐fold increase was found in binding to Z‐form brominated poly(dG‐dC).poly(dG‐dC) compared with B‐form poly(dG‐dC).poly(dG‐dC), when the polymers were coated on the plates in 0.15M NaCl. The preferential binding of SLE sera to poly(dA‐dC).poly(dG‐dT) and to Z‐DNA may be important in the formation of circulating immune complexes and subsequent vascular damage, or may provide a clue to the mechanism of production of anti‐DNA antibodies in this disease.
Renal vascular histology and morphometry in systemic sclerosis. a case–control autopsy study
Authors: Trostle David C. , Bedetti Carlos D. , Steen Virginia D. , Al‐Sabbagh M. Radwan , Zee Benny , Medsger Thomas A.
Published: February 2007

An autopsy case–control study of renal vascular histology and morphometry in systemic sclerosis (scleroderma) was performed. Thirty‐five of 70 systemic sclerosis cases had renal tissue available for study: 26 had diffuse cutaneous involvement (9 with “renal crisis” and 17 without) and 9 had limited cutaneous disease (CREST syndrome [calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias]). Age‐matched (within 10 years) and sex‐matched controls with renal specimens were obtained. New sections were cut from tissue blocks, and morphometry was completed using a Zeiss Image Analyzer. Using analysis of variance, the intimal area (Ai) was significantly increased (intimal thickening) in small and medium‐sized arteries of patients with diffuse scleroderma and in small arteries of CREST patients, compared with those in controls, while a decreased medial area (Am) was seen consistently in all groups. The proportion of the vessel wall occupied by intima (Ai:[Ai + Am]) was significantly greater in all vessel size groups in patients with diffuse scleroderma compared with that in controls. The percentage of luminal occlusion was greatest in patients with diffuse disease with renal crisis. These same patients had severe edematous and mucinous intimal thickening in small and medium vessels, often in association with fibrinoid necrosis. We conclude that renal vascular structural changes are an integral part of systemic sclerosis. However, the significant differences between diffuse scleroderma patients and CREST syndrome patients, for both intimal thickening and percentage of luminal occlusion, suggest that the arterial disease in these 2 patient subsets is distinctive.
Cyclophosphamide‐induced bladder toxicity in wegener's granulomatosis
Authors: Stillwell Thomas J. , Benson Ralph C. , Deremee Richard A. , Mcdonald Thomas J. , Weiland Louis H.
Published: February 2007

In a series of 111 patients with Wegener's granulomatosis who were given cyclophosphamide therapy, hemorrhagic cystitis, diagnosed on the basis of gross hematuria or at cystoscopy (or both), developed in 17 (15%). Most of these patients recovered uneventfully, with or without the discontinuation of cyclophosphamide, but 4 patients suffered a significant loss of blood, and bladder carcinoma developed in 3. New microhematuria also occurred in 52 patients (47%). The dose and duration of cyclophosphamide were greater in the group that had urotoxicity. Long‐term followup of patients with hemorrhagic cystitis is mandatory for the detection of late recurrences or the development of bladder malignancy. New therapies are being directed at protecting the bladder from urotoxicity during cyclophosphamide treatment.
Two ro (ss‐a) autoantibody responses in systemic lupus erythematosus
Authors: Hamilton Robert G. , Harley John B. , Bias Wilma B. , Roebber Marianne , Reichlin Morris , Hochberg Marc C. , Arnett Frank C.
Published: February 2007

Autoantibodies to Ro (SS‐A), La (SS‐B), and Sm/nuclear RNP were quantitated by enzyme‐linked immunosorbent assay in 106 white patients with systemic lupus erythematosus. Two Ro autoantibody subgroups were identified that differed quantitatively, genetically, and clinically. The subgroup having anti‐Ro only demonstrated significantly lower mean anti‐Ro levels than did the subgroup with concomitant anti‐La and showed a strong association with the linked HLA alleles DR2 and DQw1. The anti‐Ro with anti‐La sub‐group was associated with the linked HLA alleles B8, DR3, DRw52, and DQw2 (DR3 was primary), and this subgroup consisted of patients with older ages at disease onset, sicca complex, and less renal involvement. Overall, the relative risk (RR) for having anti‐Ro was highest in HLA‐DR2/DR3 heterozygotes compared with non‐DR2/DR3 heterozygotes (RR 15) and all other DR combinations (RR 7), suggesting a compound effect of 2 immune responses. Heterozygotes for HLA‐DQw1/DQw2 demonstrated significantly higher mean levels of anti‐Ro, which may be indicative of trans gene interaction at HLA‐DQ. These data suggest the hypothesis that HLA genes exert their major effects on Ro/La autoantibody subsets of systemic lupus erythematosus.
Antibody to threonyl–transfer rna synthetase in myositis sera
Authors: Targoff Ira N. , Arnett Frank C. , Reichlin Morris
Published: February 2007

The prevalence and clinical correlations of antithreonyl–transfer RNA synthetase (anti–PL‐7), as well as the relationship of anti–PL‐7 to anti–histidyl–transfer RNA synthetase (anti–Jo‐1) were studied in 109 sera from patients with myositis. Inhibition of threonine aminoacylation was used to screen for anti–PL‐7. Sera from 3 patients, 2 with polymyositis and 1 with polymyositis–overlap syndrome, and a fourth serum from a patient with dermatomyositis, which was previously found to contain anti–PL‐7, inhibited >90% of activity (3.7% of 109 sera). All 4 sera reacted strongly in an enzyme‐linked immunosorbent assay with enzyme that was either affinity purified with anti–PL‐7 or was biochemically purified. There was no indication of cross‐reactivity by aminoacylation inhibition or, for most sera, by enzyme‐linked immunosorbent assay. Anti–PL‐7 is an uncommon myositis‐associated antibody that is independent of anti–Jo‐1, but is directed at a functionally related enzyme.
Progressive depletion of hyaluronic acid in early experimental osteoarthritis in dogs
Authors: Manicourt Daniel Henri , Pita Julio Cesar
Published: February 2007

The hyaluronic acid (HA) content of articular cartilage was studied in early experimental osteoarthritis (OA) in 16 normal dogs. The anterior cruciate ligament in the right knees of the dogs was transected; their left knees served as sham operated controls. The animals were killed at 7 and 14 weeks postsurgery. Although their total hexuronate, and thus proteoglycan, content remained unaltered during the period of study, the different weight‐bearing areas of the OA knees displayed a progressive and significant decrease in HA content. We found no differences in the molecular weight and in vitro aggregating capacity of the HA molecules from OA cartilage versus those from control cartilage. This early relative depletion of HA could contribute significantly to the biochemical alterations of OA cartilage. Furthermore, it appears to be a good parameter for the differentiation of changes related to OA and changes related to aging.
Identification of cartilage matrix glycoprotein in synovial fluid in human osteoarthritis
Authors: Fife Rose S.
Published: February 2007

Cartilage matrix glycoprotein (CMGP) is a high molecular weight protein found in hyaline cartilage and fibrocartilage. It consists of disulfide‐bonded subunits, each with an apparent molecular weight of 116, 000. Fragmentation of CMGP is noted in extracts of osteoarthritic canine cartilage. CMGP has been identified in the serum and synovial fluid of dogs with experimentally induced osteoarthritis. It has now been identified in synovial fluid from osteoarthritic human joints, but not in synovial fluid from joints of patients with other arthritides or joint abnormalities. The possible significance of CMGP in synovial fluid in human osteoarthritis is discussed.
Polymyalgia rheumatica: a syndrome associated with hla–dr4 antigen
Authors: Cid Maria‐Cinta , Ercilla Guadalupe , Vilaseca Jaume , Sanmarti Raimon , Villalta Jaume , Ingelmo Miguel , Urbano‐Marquez Alvaro
Published: February 2007

HLA class II antigens were determined in 65 patients with biopsy‐proven giant cell arteritis (GCA). An increase in DR4 antigen frequency was found in the patients (40%) compared with that in 200 healthy controls (20%) (Pcorr < 0.05). DR4 was significantly more frequent in GCA patients with polymyalgia rheumatica (PMR) than in those without PMR (58.8% versus 19.3%) (P < 0.005). HLA–DR4 frequency in GCA patients without PMR was similar to that in the control population (20%). Patients with severe, disabling PMR had DR4 more frequently (90%) than did those with moderate symptoms who required medical care because of cranial arteritis manifestations (41.6%) (P < 0.05). We conclude that, in GCA patients, association with DR4 is mainly related to the manifestation of the disease as PMR. We discuss clinical and immunogenetic similarities between PMR and other DR4‐associated rheumatic disorders. Common immunopathogenic mechanisms leading to clinical overlap among them are suggested.
Use of t cell cloning to detect in vivo mutations induced by cyclophosphamide
Authors: Palmer Robert G. , Smith‐Burchnell Caroline A. , Pelton Bryan K. , Hylton Winsome , Denman A. Michael
Published: February 2007

By cloning T cells, mutations at the hypoxanthine‐guanine phosphoribosyltransferase locus were quantified in peripheral blood lymphocytes of 12 patients with connective tissue diseases receiving long‐term cyclophosphamide. Frequency of mutation was higher than in control subjects and was related to the duration of therapy; therefore, some cells with mutations are long‐lived, and these cells accumulate in the peripheral circulation. Mutation frequency was also independently related to age. The results indicate that even low doses of cyclophosphamide are mutagenic and may explain, in part, why these patients are at risk of drug‐induced malignancy.
Repeat radiation synovectomy with dysprosium 165—ferric hydroxide macroaggregates in rheumatoid knees unresponsive to initial injection
Authors: Vella Michael , Zuckerman Joseph D. , Shortkroff Sonya , Venkatesan Prasanna , Sledge Clement B.
Published: February 2007

Because of failure to fully respond to an initial intraarticular injection of dysprosium 165–ferric hydroxide macroaggregates, 17 patients with seropositive rheumatoid arthritis underwent repeat radiation synovectomy using this agent. Of the 13 patients who were evaluated 1 year later, 54% (7 knees) had good results, 31% (4 knees) had fair results, and 15% (2 knees) had poor results. The initial lack of significant benefit from radiation synovectomy did not appear to preclude a favorable response to a second injection.
Neuromuscular histopathology in (new zealand black x new zealand white)f1 and MRL‐lpr/lpr autoimmune mice: Models for skeletal muscle involvement in connective tissue disease
Authors: Rosenberg Neil L.
Published: February 2007

Skeletal muscle from (New Zealand black x New Zealand white)F1 and MRL‐lpr/lpr mice was examined for histopathologic abnormalities. Although young animals had no muscle abnormalities, older mice in both strains had the following histopathologic abnormalities: perimysial/endomysial inflammation, acute simple denervation, muscle degeneration/necrosis, and an increase in internal nuclei. MRL‐lpr/lpr mice had the following additional histopathologic abnormalities: inflammatory vascular disease (vasculitis), central myofibrillar loss, fascial inflammation, and tubular aggregates. These abnormalities are comparable with those seen in human connective tissue diseases, particularly the association with inflammation. These mouse strains provide good animal models for the study of immunopathologic processes of skeletal muscle associated with connective tissue disease.
Morphologic characteristics of developing osteoarthrotic lesions in the knee cartilage of str/in mice
Authors: Schünke Michael , Tillmann Bernhard , Brück Martina , Müller‐Ruchholtz Wolfgang
Published: February 2007

The development of osteoarthrotic cartilage lesions in the knee joints of male STR/IN mice was studied with respect to their histologic appearance and their various localizations in the joint. Spontaneous articular cartilage degeneration on the medial portion of the tibial plateau was considered to be the initial event. Continued loss of cartilage subsequently led to a pronounced instability of the knee joint, with a varus deformity. This was followed by medial patellar luxation with corresponding osteoarthrotic lesions at the facies patellaris femoris. The most marked osteoarthrotic cartilage degeneration developed on the medial tibial condyle and at the facies patellaris femoris of the femoropatellar joint. Histologic examination of the osteoarthrotic defects in these two regions revealed distinct morphologic differences with respect to formation of chondrocyte clusters, tendency to regeneration, and proliferation reactions. Lectin binding experiments in normal articular cartilage revealed regional differences regarding the presence or absence of keratan sulfate in the extracellular matrix. The lack of keratan sulfate in tibial cartilage might reflect its tendency to degenerate spontaneously. It is therefore suggested that male STR/IN mice are particularly useful for studying two different types of osteoarthrosis, one due to a biomechanically induced instability (patellar luxation) and one due to biochemical changes (absence of keratan sulfate) of still unknown pathogenesis.
Acromegalic arthropathy
Authors: Layton Mark W. , Fudman Edward J. , Barkan Ariel , Braunstein Ethan M. , Fox Irving H.
Published: February 2007

Arthropathy was assessed in 19 patients with active acromegaly. Axial or peripheral arthropathy was present in 10 patients, was located most often in large joints or the lumbosacral spine, and was osteoarthritic in nature. The mean duration of acromegaly in patients with arthropathy was 21.6 years, while the mean duration in patients without arthropathy was 7.9 years. A mild‐to‐moderate improvement in symptoms, estimated functional ability, and crepitus occurred in 8 of 9 patients who were prospectively examined during therapy to lower production of growth hormone. We conclude that this therapy did improve the symptoms of acromegalic arthropathy. Whether objective structural improvements occur remains unclear.
Anticardiolipin antibodies in lyme disease
Authors: Mackworth‐Young C. G. , Harris E. N. , Steere A. C. , Rizvi F. , Malawista S. E. , Hughes G. R. V. , Gharavi A. E.
Published: February 2007

Sera from 28 patients with Lyme disease were tested for the presence of anticardiolipin antibodies (ACLA). Seven serum samples had elevated levels of IgM ACLA, and 4 had elevated levels of IgG ACLA. Higher IgM ACLA positivity tended to be associated with neurologic disease, and IgM ACLA levels correlated with the specific IgM response to the infecting spirochete (P < 0.01). Absorption experiments indicated that ACLA and antispirochete antibodies are largely separate populations. Thus, ACLA may occur in patients with Lyme disease, particularly in those with neurologic abnormalities, and the production of these antibodies seems to be linked to the specific IgM response.
In vitro rheumatoid factor synthesis in patients taking second‐line drugs for rheumatoid arthritis
Authors: Olsen Nancy J. , Callahan Leigh F. , Pincus Theodore
Published: February 2007

Rheumatoid arthritis (RA) patients whose unstimulated peripheral blood mononuclear cells produce high levels of IgM rheumatoid factor (IgM‐RF) in vitro have more severe disease activity. RA patients being treated with second‐line agents, including gold salts, penicillamine, or methotrexate, tend to be low producers or nonproducers of IgM‐RF in vitro. The possibility that low production or nonproduction of IgM‐RF in vitro may be explained by treatment with second‐line agents alone, irrespective of disease activity, was analyzed in 133 RA patients whose disease status was assessed by multiple laboratory and clinical measures. The results indicate that treatment with second‐line agents and in vitro IgM‐RF synthesis are independently associated with disease activity.
An evaluation of serum osteocalcin in pacet's disease of bone and its response to diphosphonate treatment
Authors: Coulton Les A. , Preston Christopher J. , Couch Malcolm , Kanis John A.
Published: February 2007

We found that serum bone γ‐carboxyglutamic acid–containing protein (BGP) (osteocalcin) had lower sensitivity and specificity for measurement of disease activity in Paget's disease of bone than other biochemical measures of disease activity. The administration of diphosphonates induced suppression of urinary hydroxyproline excretion and a subsequent decrease in alkaline phosphatase values, but no consistent change in BGP values. Serum BGP measurements have limited value as a screening test for Paget's disease or for monitoring treatment of the disorder.
HLA–B27–associated arthropathy in childhood: long‐term clinical and diagnostic outcome
Authors: Sheerin Kathleen A. , Giannini Edward H. , Brewer Earl J. , Barron Karyl S.
Published: February 2007

We conducted HLA–B27 tissue typing assessments on 430 consecutive children whose main symptom at presentation to our clinic was arthritis/arthralgia. Eighty‐five of them (20%) had the B27 antigen. Thirty‐six of these children were reexamined after a mean followup period of 8.9 years. Although most had definable rheumatic diseases, only 2 met the New York criteria for ankylosing spondylitis (AS). Children with HLA–B27 and arthritis/arthralgia, although at increased risk of developing AS, have diverse diagnostic and clinical outcomes. The AS criteria used to diagnose the disease in adults may not be appropriate for use in children.
Livedo reticularis and peripheral gangrene associated with primary hyperoxaluria
Authors: Baethge Bruce A. , Daniel Sanusi I. , Landreneau Michael D. , Rohr Michael S. , Mcdonald John C.
Published: February 2007

We describe a 38‐year‐old man who developed livedo reticularis and peripheral gangrene after bilateral nephrectomy. Pathologic evaluation revealed extensive crystalline deposits within the walls of subcutaneous blood vessels. The diagnosis of primary hyperoxaluria was established. This case demonstrates that the vasculopathy of primary oxalosis can mimic systemic necrotizing vasculitis.
Phenotypic analysis of synovial tissue and peripheral blood lymphocytes isolated from patients with rheumatoid arthritis
Authors: Cush John J. , Lipsky Peter E.
Published: February 2007

Cytofluorometric analysis was performed to characterize the surface phenotype and activation status of freshly isolated synovial tissue lymphocytes (STL) and peripheral blood lymphocytes (PBL) from 7 patients with rheumatoid arthritis (RA). Proliferative synovium was enzymatically digested to obtain tissue‐derived lymphocytes. Indirect immunofluorescent staining of patient PBL and STL with a variety of monoclonal antibodies failed to reveal a consistent alteration in the number of CD4+ (helper/inducer) PBL or STL. However, there was a significant decrease in the number of CD8+ (suppressor/cytotoxic) cells in rheumatoid STL (P < 0.05). A significant reduction in the density of the T cell differentiation antigens CD3 and CD4 was observed in RA PBL and STL, compared with control PBL. These differences in antigen density were not seen when normal PBL were subjected to the same enzymatic digestion. Both RA PBL and STL manifested increased expression of HLA–DR antigens, without augmentation of interleukin‐2 receptor expression. Alterations in the expression of the T cell differentiation antigens and activation antigens by patient PBL closely paralleled the abnormalities observed in STL. In contrast, STL of patients with RA exhibited an increase in the expression of the adhesion‐related glycoproteins (leukocyte function‐associated 1 [LFA‐1] and very late activation 1 [VLA‐1] antigens), not observed with autologous PBL. These studies demonstrate that lymphocytes isolated from the synovial tissues of RA patients bear an activated phenotype, exemplified by the modulation of CD3 and CD4 and the expression of HLA‐DR. The enhanced expression of the adhesion molecules LFA‐1 and VLA‐1 by STL may play a role in the localization of these cells to the inflamed synovium.
The incidence of rheumatoid arthritis is predicted by rheumatoid factor titer in a longitudinal population study
Authors: Puente Antonio Del , Knowler William C. , Pettitt David J. , Bennett Peter H.
Published: February 2007

Rheumatoid factor (RF) is often detected in subjects who do not have rheumatoid arthritis (RA). To determine if the presence of RF is predictive of the development of RA, 2, 712 Pima Indians of Arizona, 20 years of age or older, initially without RA, have been observed for up to 19 years with biennial examinations. These included a medical history, physical examination of the joints, radiographs, and RF determination by sheep cell agglutination test. During the study period, 70 new cases of RA developed. When the population at risk was stratified by RF titer, with reclassification at subsequent examinations if the RF titer changed, the age‐ and sex‐adjusted incidence of RA increased with higher titers of RF. The incidence of RA (in cases per 1,000 person‐years) according to RF titer was 2.4 (RF titer <1:2); 6.7 (titer 1:2–1:16); 11.0 (titer 1:32–1:256); and 48.3 (titer >1:256) (P < 0.001). The same trend was also found within each age and sex group, and within groups defined by the number of American Rheumatism Association criteria present before the definite diagnosis. We conclude that the presence of RF, in subjects without RA, is a risk factor for the development of RA, and that this risk is related to the RF titer. It is also suggested that RF may represent a marker of the earliest phases of the pathogenetic process of RA, that may be detectable before the appearance of other features that permit a clinical diagnosis.
Self‐evaluation processes and adjustment to rheumatoid arthritis
Authors: Blalock Susan J. , Vellis Brenda Mcevoy De , DeVellis Robert F. , Sauter Suzanne Van H.
Published: February 2007

In this study we examined whether the impact of rheumatoid arthritis (RA) on psychological well‐being is mediated by the way patients evaluate their physical abilities. The primary focus was on patients' satisfaction with their physical abilities and the types of comparisons that patients make between themselves and other people (i.e., social comparisons) when evaluating their abilities. Seventy‐five women with RA were interviewed. Findings indicate that satisfaction with one's physical abilities appears to mediate the relationship between physical and psychological impairment. Furthermore, satisfaction was associated not only with one's abilities per se, but also with the types of comparisons patients made when evaluating their abilities. These findings help explain differences in the levels of psychological well‐being noted among individuals with the same degree of physical impairment.
Effects of recombinant human interleukin‐1β on rabbit articular chondrocytes
Authors: Chin Jia E. , Lin Yuan
Published: February 2007

Using an in vitro model, we characterized the production of prostaglandin E2, 6‐keto‐prostaglandin F1α, and thromboxane B2 by normal rabbit articular chondrocytes stimulated by interleukin‐1β. The prostanoids were produced in a dose‐ and time‐dependent manner, which was sensitive to actinomycin D and cycloheximide. Interleukin‐1 also had a pronounced, but reversible, cytostatic effect on chondrocytes, which was not attributable to prostanoid or polyamine synthesis.
Jaw deformity caused by juvenile rheumatoid arthritis and its correction
Authors: Myall Robert W. T. , West Roger A. , Horwitz Heidi , Schaller Jane G.
Published: February 2007

An underdeveloped mandible and resulting micrognathia and malocclusion may occur in some children with juvenile rheumatoid arthritis. Combined orthodontic and surgical procedures can now greatly improve esthetics and function in such children. We describe corrective treatment and followup of 7 patients.
Synovial fibroblast‐like cells synthesize seven proteins of the complement system
Authors: Katz Yitzhak , Strunk Robert C.
Published: February 2007

Fibroblast‐like cells from synovial tissue obtained during arthroscopy in 4 young adults with recent knee trauma were biosynthetically labeled with 35S‐methionine, and protein production was quantitated by immunoprecipitation and sodium dodecyl sulfate—polyacrylamide gel electrophoresis. Synovial fibroblast‐like cells synthesized C1r, C1s, C1 inhibitor, C2, C3, factor B, and factor H, all with the same sizes and subunit structures as the proteins synthesized in skin fibroblasts. The capacity to synthesize these proteins was not lost with passages or freeze‐thawing. Gamma‐interferon stimulation increased synthesis of all 7 proteins. Lipopolysaccharide increased synthesis of only C3 and factor B. Unlike in whole rheumatoid tissue, C4 and C5 were not detected. Synovial lining cells may be an important source of local complement for participation in local defense or development of pathologic states.
Synovial fluid eosinophilia in lyme disease
Authors: Kay Jonathan , Eichenfield Andrew H. , Athreya Balu H. , Doughty Robert A. , Ralph Schumacher H.
Published: February 2007

We describe three 14‐year‐old boys who developed synovial fluid eosinophilia associated with Lyme disease. One patient, with arthritis that began in 1975, had the first documented case of Lyme disease in New Jersey. Lyme disease should be considered when eosinophilia is noted on analysis of synovial fluid from patients with undiagnosed arthritis.
Plasma and bone osteocalcin levels in rats with type ii collagen—induced arthritis
Authors: Tanaka Hiroshi , Shirota Hiroshi , Kuwada Manabu , Terato Kuniaki , Katayama Kouichi
Published: February 2007

Osteocalcin levels in plasma and bone were measured by enzyme immunoassay in rats with arthritis induced by immunization with type II collagen and in untreated control rats. Compared with levels in control rats, the plasma levels of osteocalcin in arthritic rats were markedly decreased 1–3 weeks after immunization; during weeks 8–14, these levels were significantly increased. The osteocalcin content of tarsal bones changed in parallel with the plasma levels. These data suggest that osteocalcin levels in the plasma of arthritic rats reflect alterations in bone formation activity.
A retrospective study of antibodies against basement membrane antigens (type iv collagen and laminin) in patients with primary and secondary raynaud's phenomenon
Authors: Gabrielli Armando , Montroni Maria , Rupoli Serena , Caniglia Maria Luisa , Delustro Frank , Danieli Giovanni
Published: February 2007

Antibodies against type IV collagen were detected in the sera of 21% of patients with primary Raynaud's phenomenon (PRP) and 68% of patients with systemic sclerosis. Sera from 25% of the PRP patients and 48% of systemic sclerosis patients displayed antibodies to laminin. Eighty percent of the patients with PRP and antibodies to basement membrane antigens developed additional serologic or clinical manifestations, whereas only 16% of patients with PRP and no anti—basement membrane antibodies developed such manifestations.
Quantitative microfocal radiographic assessment of progression in osteoarthritis of the hand
Authors: Buckland‐Wright J. C. , Macfarlane D. G. , Lynch J. A. , Clark B.
Published: February 2007

We studied 32 patients with osteoarthritis who had 5× macroradiographs taken of their wrists and hands at 6‐month intervals over an 18‐month period. The higher magnification and resolution of microfocal radiography permitted the quantitative detection of progressive changes in 4 different features: subchondral sclerosis, the number and size of osteophytes, juxtaarticular radiolucencies, and joint space narrowing. Compared with normal control subjects, subchondral cortical thickness was greater in all patients at entry and showed a variable degree of change over the study period. Osteophytes and juxtaarticular radiolucencies were present in all patients at study entry; by the end of the study, osteophytes had increased in number and area, and juxtaarticular radiolucencies had increased in area, but not in number. At entry, 44% of the patients had joint space narrowing significantly greater than that in the control subjects; by 18 months, this proportion increased to 65%. No correlation was found between subchondral sclerosis, osteophytes, juxtaarticular radiolucencies, and joint space narrowing. We conclude that in osteoarthritis of the hand, the bony changes have progressed significantly before the occurrence of radio‐graphically evident joint space narrowing indicative of cartilage thinning.
Pharmacokinetics of methotrexate administered by intramuscular and subcutaneous injections in patients with rheumatoid arthritis
Authors: Brooks Paul J. , Spruill William J. , Parish Roy C. , Birchmore Daniel A.
Published: February 2007

The serum concentrations and the pharmacokinetics of low‐dose methotrexate (MTX) were compared after both intramuscular (IM) and subcutaneous (SQ) injections in 5 patients with rheumatoid arthritis. Values for the observed peak concentration, the time to the observed peak concentration, and the area under the time versus concentration curve for IM injections were not significantly different from these values for SQ injections. These results suggest that IM and SQ are interchangeable routes of administration. SQ administration may be a more convenient and less painful way of administering low‐dose MTX.
Antigenicity of a recombinant Ro (SS‐A) fusion protein
Authors: James Judith A. , Daryl Dickey W. , Fujisaku Atsushi , O'Brien Charles A. , Deutscher Susan L. , Keene Jack D. , Harley John B.
Published: February 2007

The antigenicity of the 60‐kd human Ro (SS‐A) synthesized in vitro from its complementary DNA as a β‐galactosidase fusion protein (β‐gal—Ro) was evaluated by Western blotting. In this analysis, almost all the anti‐Ro (SS‐A)‐positive sera that bound β‐gal‐Ro also bound affinity‐purified 60‐kd human Ro (SS‐A) (P > 0.005). Three of the 27 anti‐Ro (SS‐A) precipitinpositive sera, however, did not show reactivity on Western blot analysis, which suggests that in some sera, antigenicity to Ro (SS‐A) is destroyed by denaturation. Of the 22 sera that were reactive with β‐gal‐Ro, 2 were not reactive with affinity‐purified human Ro (SS‐A). Two serum samples that did not react with β‐gal‐Ro were also reactive with affinity‐purified human Ro (SS‐A). Nevertheless, except for a small percentage of Ro (SS‐A) precipitin‐positive sera, the frequency of antibody binding to the fusion protein was similar to the frequency of binding to the purified antigen in Western blots. Recombinant Ro (SS‐A) antigen may therefore be valuable in the serologic evaluation of anti‐Ro (SS‐A) autoantibodies.
High prevalence of iga rheumatoid factor in severe polyarticular‐onset juvenile rheumatoid arthritis, but not in systemic‐onset or pauciarticular‐onset disease
Authors: Walker Sharyn M. , Mccurdy Deborah K. , Shaham Bracha , Brik Riva , Wietting Heidi , Arora Yogesh , Lehman Thomas J. A. , Hanson Virgil , Bernstein Bram
Published: February 2007

The presence of IgA rheumatoid factor (IgA‐RF) has been correlated with severe joint disease in adult rheumatoid arthritis (RA), but IgA‐RF has not been reported in juvenile rheumatoid arthritis (JRA). In the present study, IgA‐RF was assayed by an enzyme‐linked immunosorbent assay and was found in the sera of 14 of 24 children (58%) with active polyarticular JRA. The presence of IgA‐RF correlated with the degree of functional disability. In contrast, IgA‐RF was not found in the sera of systemic‐onset disease patients, regardless of the degree of dysfunction. IgA‐RF was detected in only 1 patient with pauciarticular disease, despite the fact that several patients in this group had severe disease. The presence of IgA‐RF in polyarticular JRA did not correlate with serum IgA levels, but did correlate with the presence and the level of serum IgM‐RF. Thus, the presence of IgA‐RF appears to be specific for polyarticular JRA, and shows a correlation with severe disease in this group.
Cartilage inorganic pyrophosphate elaboration is independent of sulfated glycosaminoglycan synthesis
Authors: Ryan Lawrence M. , Kurup Indira , Mccarty Daniel J. , Cheung Herman S.
Published: February 2007

Inorganic pyrophosphate (PPi), a product of glycosaminoglycan synthesis, may be cosecreted with matrix proteoglycan to reach the extracellular site where calcium pyrophosphate dihydrate crystals form. To test this hypothesis, sulfated glycosaminoglycan synthesis by articular cartilage in culture was stimulated or inhibited while the effect on extracellular PPi was measured. When stimulated by 0.8 mM xyloside to increase 35SO4 incorporation (mean ± SEM % of control 183 ± 16, n = 5), PPi accumulation changed little (from 54 ± 6 pmoles/mg to 63 ± 8 pmoles/mg of cartilage wet weight). Inhibition of sulfation with monensin or di‐ethylcarbamazine disproportionately lowered 35SO4 incorporation compared with PPi elaboration. Using 60 mM diethylcarbamazine, PPi production was preserved (105 ± 8% mean ± SEM) compared with control cultures, while sulfation was markedly inhibited (7 ± 1%). This dissociation of sulfate incorporation and PPi secretion indicates that it is not likely that glycosaminoglycan sulfation is the source of the PPi that escapes from chondrocytes to participate in the formation of extracellular crystals.
Chronic acquired immunodeficiency syndrome‐associated arthritis: a synovial ultrastructural study
Authors: Bentin Jacques , Feremans Walter , Pasteels Jean‐Lambert , Hauzeur Jean‐Philippe , Menu Roberte , Appelboom Thierry
Published: February 2007

We describe a patient who developed acquired immunodeficiency syndrome‐related complex, complicated by chronic, symmetric polyarthritis. Synovial biopsy showed large areas of plasma cell infiltration subjacent to the synovial lining. Ultrastructural study demonstrated tubuloreticular structures within endothelial cells, crystal‐like inclusions in plasma cells, and virus‐like particles located around synoviocyte fragments. Although immunologic and morphologic studies did not permit classification of these virus‐like structures, the role of these possible virions in the pathogenesis of the observed synovitis remains to be determined. Surprisingly, the patient's chronic arthritis resolved with anti‐retroviral treatment (azidothymidine; AZT).
High frequency of fibromyalgia in patients with chronic fatigue seen in a primary care practice
Authors: Goldenberg Don L. , Simms Robert W. , Geiger Ann , Komaroff Anthony L.
Published: February 2007

We administered a standardized history questionnaire and performed a tender point examination on 27 patients with debilitating fatigue of at least 6 months duration, seen in a primary care practice, as well as on 20 patients with fibromyalgia. Sixteen of the 27 patients with chronic fatigue met the full criteria for the working case definition of chronic fatigue syndrome (CFS). Eight patients with chronic fatigue denied having any current persistent, diffuse musculoskeletal pain, and their tender point scores were similar to those in 10 normal control subjects. In contrast, 19 patients with chronic fatigue (70%) had persistent, diffuse musculoskeletal pain. The results of their tender point examinations were similar to those of the patients with fibromyalgia. Thus, the majority of these patients with debilitating chronic fatigue, including those who met criteria for CFS, met the historical and tender point diagnostic criteria for fibromyalgia. The presence of current musculoskeletal pain will identify those CFS patients who have fibromyalgia.
Synovitis in angioimmunoblastic lymphadenopathy with dysproteinemia simulating rheumatoid arthritis
Authors: Boumpas Dimitrios T. , Wheby Munsey S. , Jaffe Elaine S. , Steinberg Alfred D. , Klippel John H. , Balow James E.
Published: February 2007

We describe a patient with angioimmunoblastic lymphadenopathy with dysproteinemia who developed a symmetric, rheumatoid‐like, peripheral polyarthritis. Radiographs of the involved joints revealed soft tissue swelling without erosions or cartilage loss. Rheumatoid factor and fluorescent antinuclear antibodies were negative, and C‐reactive protein and erythrocyte sedimentation rate were normal. Synovial fluid analysis showed an inflammatory effusion (white blood cell count of 3,500/mm3, with 76% polymorphonuclear leukocytes). A closed synovial biopsy of the wrist revealed a mononuclear infiltrate consistent with angioimmunoblastic lymphadenopathy with dysproteinemia. Monthly parenteral chemotherapy treatment with high‐dose methyl‐prednisolone and cyclophosphamide resulted in remission of all manifestations of disease, including arthritis.
Early‐onset primary osteoarthritis and mild chondrodysplasia
Authors: Katzenstein Paul L. , Malemud Charles J. , Pathria Mini N. , Carter John R. , Sheon Robert P. , Moskowitz Roland W.
Published: February 2007

Three generations of a nonconsanguineous family with premature onset of primary (idiopathic) osteoarthritis (OA) were studied for clues to the etiopathogenesis of their disorder. Articular symptoms began in their second and third decades of life and involved multiple joints, both typical and atypical for primary OA. Radiographs of the majority of involved peripheral joints showed abnormalities typical of primary OA. Evidence of chondrodysplasia was found in the spines. Pathologic examination of femoral heads obtained at total hip arthroplasty from 3 affected family members showed moderate to severe OA. Articular cartilage proteoglycans from these specimens were evaluated for aggregatability with hyaluronic acid, levels of chondroitin sulfate and keratan sulfate, and core protein structure. The results from each patient's specimen differed from the results of the other specimens. We conclude that this family's disorder, primary OA associated with a mild chondrodysplasia, was a late‐onset overlap form of an epiphyseal dysplasia, that a defect common to hyaline articular and physeal cartilage was primary, and that a single structural proteoglycan abnormality was not likely to be the underlying cause.
Detection of serum antibodies to retroviral proteins in patients with primary sjögren's syndrome (autoimmune exocrinopathy)
Authors: Talal Norman , Dauphinée Michael J. , Dang Howard , Alexander Steve S. , Hart Darrenn J. , Garry Robert F.
Published: February 2007

Primary Sjögren's syndrome (SS) is considered a benign autoimmune disease; it is characterized by lymphoid infiltration of salivary and lacrimal glands, often accompanied by the presence of serum autoantibodies, particularly anti‐Ro (SS‐A) and anti‐La (SS‐B). There are important immunologic similarities between primary SS and acquired immunodeficiency syndrome. To investigate for a possible immune response to retroviral proteins in primary SS, we performed immunoblotting against human immunodeficiency virus‐1 (HIV‐1) proteins using sera from 47 patients with primary SS. Moderate‐to‐strong reactivity, suggesting the presence of serum antibodies, was found in 14 patients (30%). Of 120 normal subjects, only 1 showed moderate positivity. All 14 positive SS sera reacted against p24 (gag) but failed to react against gp41 or gp120 (env). This response did not reflect hypergammaglobulinemia since immunoglobulin concentrations among the 29 SS patients studied were the same in sera that contained and sera that did not contain anti‐gag reactivity. Two sera also reacted against p17 gag. Four reacted against HIV‐2 core proteins, but none reacted with core proteins of human T lymphotropic virus‐I. Only 1 of the 14 sera reacted against Ro (SS‐A), and 1 other reacted against La (SS‐B). These results identify a subset of SS patients characterized by 1) the presence of serum antibodies to HIV‐1 group‐specific, but not type‐specific, proteins, and 2) the relative absence of anti‐Ro (SS‐A) and anti‐La (SS‐B) autoantibodies. In this latter respect, these SS patients constitute a subpopulation that resembles patients with HIV‐induced SS‐like disease.
The expression of C3b receptors in the differentiation of discoid lupus erythematosus and systemic lupus erythematosus
Authors: Tausk Francisco , Harpster Elaine , Gigli Irma
Published: February 2007

We studied the expression of the C3b receptor, CR1, on erythrocytes (E‐CR1) of patients who, in spite of having mild systemic symptoms, were diagnosed as having discoid lupus erythematosus and followed accordingly. We found that E‐CR1 was markedly reduced in these patients, similar to that seen in patients with systemic disease. In contrast, those patients with completely asymptomatic discoid lupus erythematosus had the same expression of E‐CR1 as the normal population.