bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of polymorphonuclear leukocytes with immune complexes trapped in rheumatoid articular cartilage
Authors: Ugai Kazuhiro , Ishikawa Hitoshi , Hirohata Kazushi , Shirane Hirofumi
Published: February 2007

When rheumatoid articular cartilage samples were incubated with normal polymorphonuclear leukocytes (PMN) in vitro, large numbers of PMN were seen attached to the articular surface. As observed by electron microscopy, significant numbers of these cells invaded the cartilage tissue and phagocytosed amorphous material which presumably contained immune complexes. In control cartilage from osteoarthritic, pyogenic, and normal subjects, only a few PMN were attached to the articular surface after incubation with PMN. These results demonstrate that immune complexes trapped in the superficial region of the rheumatoid articular cartilage may play an important role in the destruction of cartilage by the release of lysosomal enzymes from PMN.
Decrease of the okt8 positive t cell subset in polymyalgia rheumatica
Authors: Benlahrache Charif , Segond Patrick , Auquier Louis , Bouvet Jean‐Pierre
Published: February 2007

Peripheral T cell populations were investigated in 35 patients suffering from polymyalgia rheumatica. The total number of T cells was low compared with those of a control group of similar age (P < 10−3). This decrease was demonstrated by using both classic E‐rosette and monoclonal antibody techniques (OKT3, and OKT4 + OKT8) and was shown to be secondary to a selective T8 defect (P < 10−9). There was no correlation between the decrease in T8 (a cytotoxic suppressor T cell subset) and steroid therapy, disease activity, and temporal arteritis, nor between this decrease and the TyM percentage and the presence of circulating immune complexes (CIC). The TyM cell percentage was low in the patient group (P < 10−5) and correlated with the presence of detectable CIC (P < 0.05). In contrast to the T8 and TyM defects, concanavalin A‐stimulated cells from 5 selected patients were found capable of suppressing in vitro anti‐trinitro‐phenyl response. This suppression was found in both autologous and allogeneic experiments. From these data one can assume that an immune anomaly (T8 defect) could be the origin of CIC and the disease occurrence.
Anti‐fab' antibodies in rheumatoid arthritis
Authors: Birdsall Holly H. , Lidsky Martin D. , Rossen Roger D.
Published: February 2007

High levels of anti‐immunoglobulins that react with Fab′ fragments of IgG have been observed in sera of patients with rheumatoid arthritis (RA). To determine how much of these anti‐Fab′ antibodies are incorporated within immune complexes (IC), we added 125I‐Fab′ to sera and then measured the amount of labeled Fab′ that could be precipitated by adding polyethylene glycol (PEG). Sera were either maintained at neutral pH during this procedure or acidified (pH 3) to dissociate IC. Acidification permitted the 125I‐Fab′ an equal chance to compete with other endogenous antigens for anti‐Fab′ antibodies, once excess hydrogen ion was removed. Quantities of anti‐Fab′ in sera of 20 seropositive RA patients were greater than in sera of 43 age‐and sex‐matched healthy controls, as measured by this assay and by a solid phase radioimmunoassay. However, significantly less anti‐Fab′ antibody was incorporated in ICs in the RA patients' sera. Supernatants from cultured peripheral blood lymphocytes of RA patients also contained relatively more “free” and less “hidden” anti‐Fab′ than culture supernatants from controls. Thus there appear to be qualitative as well as quantitative differences in the anti‐Fab′ antibodies synthesized by RA patients. This may reflect different proportions of IgM and IgG anti‐Fab′ in their sera, differences in the average avidity of these antibodies, or differences in the reciprocal relationships within the idiotypic network that result in release of antibodies by certain antibody‐producing cells, but not by clones that produce complementary idiotypes.
Phosphorylation of proteoglycans from human articular cartilage
Authors: Anderson Roger S. , Schwartz Edith R.
Published: February 2007

Previous studies have shown that sulfated proteoglycans from human articular and epiphyseal cartilage were phosphorylated. These macromolecules contribute to the stiffness and resiliency of this tissue. We demonstrate here that the phosphate moieties are an integral part of proteoglycan subunits. Specifically, evidence is presented which indicates that proteoglycan monomers contain 3 to 4 phosphate moieties per core protein and that these appear to exist as phosphoserine residues. Furthermore, the data illustrate that human articular cartilage also contains more than 20 different phospho‐proteins, some of which are closely associated with proteoglycan aggregates. Proteoglycan subunits were purified from extracts of articular cartilage or from media fractions which had been used to label tissue specimens with 32P‐orthophosphate. Chemical and radiographic analyses revealed that the phosphate concentration with respect to sulfate and uronic acid content remained constant when purified proteoglycan monomers were subjected to equilibrium ultracentrifugation and size‐exclusion chromatography. That the phosphate moieties were bound to proteoglycan monomers via monoester linkages was indicated by the release of 32P‐orthophosphate from proteoglycan subunits incubated under mild alkaline conditions or reacted with acid or alkaline phosphatases. Identification of serine residues in the core protein as the sites of phosphorylation was made by autoradiography of thin layer plates on which hydrolyzed samples of purified 32P‐proteoglycan sub‐units had been subjected to 2‐dimensional electrophoresis/chromatography. Quantification of 3 to 4 phosphate moieties per core protein of 200,000 daltons was made by chemical analysis of inorganic phosphate released from proteoglycans by acid hydrolysis.
Cytokine modulation of chondrocyte proteinase release
Authors: Herman Jerome H. , Greenblatt David , Khosla Ramesh C. , Appel Alan M.
Published: February 2007

Nonenzymatic, trypsin sensitive cytokines derived from lectin stimulated normal human mononuclear cells have been shown to induce release of proteoglycan and collagen degrading proteinase activity from chondrocytes in cartilage organ and isolated suspension culture systems. Active chondrocyte protein and RNA synthesis were required to induce activity. Cytokines responsible were of both monocyte and T cell origin. Direct monokine catabolic induction and monokine/lectin‐triggered lymphokine inducing activity could be demonstrated. Cyclooxygenase inhibitors and direct or indirect modulation of mononuclear cell or chondrocyte cAMP levels had no effect on factor synthesis or activity. Hydrocortisone abrogated the effect. Cytokines responsible were heat labile, unaffected by reduction/alkylation or neuraminidase exposure, and stable over a pH range of 3–10.
Speckled pattern antinuclear antibodies resembling anticentromere antibodies
Authors: Fritzler Marvin J. , Valencia Don W. , Mccarty Gale A.
Published: February 2007

Two distinct nuclear antigens, designated NSpI and NSpII, have been characterized and differentiated from the centromeric antigen that reacts with sera from patients with the CREST syndrome. Both NSpI and NSpII produce a speckled pattern of indirect immuno‐fluorescence on HEp‐2 cells that resembles the pattern seen with anticentromere antibodies (ACA). They are differentiated from the ACA staining pattern by the absence of metaphase chromatin staining by NSpI antisera and by the absence of a discrete speckled pattern of staining by NSpII. Further, both NSpI and NSpII stain predominantly the peritubular nuclei of mouse kidney cryostat sections. NSpII is sensitive to trypsin, proteinase K, and HCl extraction, suggesting that it is a relatively soluble nuclear protein. NSpI was also sensitive to protease treatment but was not extracted with 0.1N HCl, suggesting that it is a tightly bound nuclear protein.
Clinical and laboratory associations of anticentromere antibody in patients with progressive systemic sclerosis
Authors: Steen Virginia D. , Ziegler Gayle L. , Rodnan Gerald P. , Medsger Thomas A.
Published: February 2007

Anticentromere antibody (ACA) was found in the serum of 4 (3%) of 120 patients with progressive systemic sclerosis with diffuse scleroderma and in 69 (49%) of 141 with progressive systemic sclerosis with the CREST syndrome variant. The 69 CREST syndrome patients with ACA were compared with the 72 CREST syndrome patients without ACA. The former were older at the onset of symptoms and significantly more frequently female (97% versus 78%, P < 0.01). Those with ACA more often had telangiectasiae of the digits (93% versus 75%) and calcinosis (55% versus 22%). These differences were also present after the groups were stratified according to duration of disease. Cutaneous involvement was similar in both degree and extent in the 2 groups; 20% of CREST patients both with and without ACA had forearm skin thickening. Pulmonary interstitial fibrosis on chest roentgenogram and restrictive disease on pulmonary function testing were significantly less frequent in the ACA patients. Gastrointestinal involvement, pulmonary arterial hypertension, and cardiac abnormalities were similar in both groups, and there has been no difference in survival between CREST syndrome patients with and without ACA. Tissue typing studies revealed a significant association between ACA and HLA‐DR1.
Treatment of raynaud's phenomenon with ketanserin, a selective antagonist of the serotonin2 (5‐HT2) receptor
Authors: Seibold James R. , Jageneau Anton H. M.
Published: February 2007

Ketanserin, a selective antagonist of the 5‐HT2 receptor, was evaluated in a 4‐week open pilot trial of 30 patients with Raynaud's phenomenon. Moderate or marked relief was reported in 15 of 18 (83%) patients with systemic sclerosis, whereas only 4 of 12 (33%) patients with Raynaud's phenomenon of other etiology received such benefit (P < 0.01). These subjective ratings were supported by the results of serial digital strain gauge plethysmography during controlled cold challenge. Additional clinical findings suggested that ketanserin therapy facilitated the healing of ischemic digital ulcerations and reduced hand edema in patients with systemic sclerosis. These findings lend support to the hypothesis that serotonin is an important element in the pathogenesis of systemic sclerosis.
Ntp pyrophosphohydrolase in human chondrocalcinotic and osteoarthritic cartilage: Further Studies on Histologic and Subcellular Distribution
Authors: Howell David S. , Martel‐Pelletier Johanne , Pelletier Jean‐Pierre , Morales Sara , Muniz Ofelia
Published: February 2007

A nucleoside triphosphate (NTP) pyrophospho‐hydrolase was previously demonstrated in human chondrocalcinotic and osteoarthritic articular cartilage. In this study, grinding and enzymatic techniques for cartilage subcellular fractionation were compared. It was shown that this enzyme was concentrated in fractions enriched in plasma membranes. The enzyme had the same activity in cartilage slices as in triton X‐100 extracts, and all of the activity was removed by preliminary treatment of cartilage slices with pronase. Histologic separation of cartilages into tangential and upper radial versus lower radial zones indicated no difference in concentrations of this enzyme. A role is postulated for this enzyme in metabolic chondrocytic plasma membrane responses to injury or destabilization from other causes, such as rapid synthesis or cell division.
Evaluation of comprehensive rehabilitation services for elderly homebound patients with arthritis and orthopedic disability
Authors: Liang Matthew H. , Partridge Alison J. , Larson Martin G. , Gall Victoria , Taylor Jennifer , Berkman Cathy , Master Robert , Feltin Marie , Taylor James
Published: February 2007

Fifty‐seven elderly homebound patients with arthritis and orthopedic disabilities were randomized to a goal‐oriented outreach rehabilitation program or to usual treatment. Although 64% of patient goals were met, there were no overall significant differences in functional scores, institutionalization, or contentment between treatment and control periods. Twenty‐three patients had maintained clinical improvement at the end of the study and some patients were dramatically improved with simple measures. The program's marginal costs were modest and consisted primarily of expenses associated with therapist's visits. The total costs of assistive devices and home modifications amounted to $1,902. Twenty‐five percent of the homebound population could benefit from such services but the actual number who would partake is small.
Anti‐f(ab′)2 antibodies that interfere with interpretation of the anti‐c3 assay for immune complexes in children with rheumatic diseases
Authors: Olds Lynne C. , Miller John J. III
Published: February 2007

Results of the solid phase F(ab')2 anti‐C3 radio‐immunoassay for immune complexes were abnormal in sera from some patients with juvenile arthritis and in many patients with other forms of chronic inflammation. However, C3 failed to block positive reactions of sera from patients even though it did block the reaction when aggregated IgG was added to normal sera. Moreover, positive sera reacted with nonspecific F(ab')2 fragments from several species. High correlation coefficients were obtained between abnormal results in the anti‐C3 assay with juvenile arthritis sera and reactions with goat, mouse, and rabbit F(ab')2, but less so with human F(ab')2. Sera from patients with systemic lupus erythematosus or cystic fibrosis had similar reactions but different species specificities. After sucrose density fractionation, the reactivity with nonspecific anti‐F(ab')2 was only in the IgG‐containing fractions, but anti‐C3 activity was in both IgG‐containing fractions and the fractions between IgG and IgM. We conclude that anti‐F(ab')2 antibodies are common in children with inflammation and may interfere with interpretation of assays using F(ab')2 anti‐C3 for detection of complexes.
A Murine Model of Polymyositis Induced by Coxsackievirus B1 (Tucson Strain)
Authors: Strongwater Steven L. , Dorovini‐zis Katerina , Ball Richard D. , Schnitzer Thomas J.
Published: February 2007

A murine model of polymyositis induced by coxsackievirus B1, Tucson strain (CVBT) is described. Intraperitoneal CVBT inoculation of CD 1 Swiss mice less than 48 hours old resulted in proximal hindquarter weakness that was first apparent 7 days after viral challenge and persisted for more than 10 weeks. Electromyographic and histologic evidence of a continuing myositis was present during this entire period of time. However, virus was not detectable later than 2 weeks post infection, despite clinical progression of disease. The finding of electromyographic and histologic abnormalities in CVBT‐infected mice, long after virus had cleared and neutralizing antibody production evoked, suggests that persistent myositis may be immunologically mediated, triggered by the initial acute viral infection.
Azathioprine versus d‐penicillamine in rheumatoid arthritis patients who have been treated unsuccessfully with gold
Authors: Paulus Harold E. , Williams H. James , Ward John R. , Reading James C. , Egger Marlene J. , Coleman Miki L. , Samuelson Cecil O. , Willkens Robert F. , Guttadauria Maria , Alarcón Graciela S. , Kaplan Stanley B. , Maclaughlin Edmund J. , Weinstein Arthur , Wilder Ronald L. , Solsky Marilyn A. , Meenan Robert F.
Published: February 2007

Two hundred six patients were entered into a prospective controlled, double‐blind, multicenter trial comparing azathioprine (AZA) 1.25–1.5 mg/kg/day with D‐penicillamine (DP) 10–12 mg/kg/day. One hundred thirty‐four patients completed 24 weeks of therapy. Improvement in nearly all efficacy variables was seen in both groups. Patients taking DP demonstrated a greater rise in hemoglobin concentration and greater fall in erythrocyte sedimentation rate than patients receiving AZA; these were the only efficacy variables with a significant difference between the treatment groups. Fewer withdrawals for adverse reactions occurred among the patients receiving AZA, but the difference was not significant. Patients receiving AZA were withdrawn from the drug mainly for abnormal liver function test results, nausea and gastrointestinal upset, and leukopenia. The main reasons for withdrawal of patients receiving DP were nausea, rash and pruritis, thrombo‐cytopenia, dysgeusia, and proteinuria.
Rheumatoid arthritis and small airways function
Authors: Mountz J. D. , Turner R. A. , Collins R. L. , Gallup K. R. , Semble E. L.
Published: February 2007

The sensitive pulmonary function tests of change in maximum expiratory flow (ΔVmax 50) and volume of isoflow were used to determine the effects of rheumatoid arthritis (RA), smoking, and α‐antitrypsin deficiency phenotypes on peripheral airways. Patients were prospectively divided into 4 groups: 14 smokers with RA, 12 nonsmokers with RA, 11 smokers without RA, and 13 nonsmokers without RA. ΔVmax 50 was the most discriminating variable and demonstrated significant small airway obstructive disease in the first 3 groups, with an additive effect in the group of smokers with RA. An increased incidence of the α‐antitrypsin‐deficient MS phenotype was seen in the RA smoker group, and this phenotype was associated with severe pulmonary disease.
The value of conventional views and radiographic magnification in evaluating early rheumatoid arthritis
Authors: Hartley Robert M. , Liang Matthew H. , Weissman Barbara N. , Sosman J. Leland , Katz Robert , Charlton John R.
Published: February 2007

Fifty‐four patients with suspected early rheumatoid arthritis had radiographs taken of their hands and wrists in 4 views (posteroanterior [PA], oblique, reverse oblique, and Brewerton) using conventional techniques and, in the PA view, using radiographic magnification. The radiographs were “masked” and presented in random order to 2 radiologists specializing in bone and joint radiology who interpreted them for malalignment, erosions, joint space narrowing, and soft tissue swelling. The PA was the best conventional view for demonstrating malalignment, joint space narrowing, and soft tissue abnormalities; the Brewerton view was better for detecting erosive disease. Radiographic magnification was more sensitive than conventional films for evaluating erosive disease, but otherwise was no better than the conventional PA view. These results help the physician choose the radiologic technique or combination of techniques that is most likely to detect specific abnormalities.
Cellular mechanism of DNA‐specific antibody synthesis by lymphocytes from systemic lupus erythematosus patients
Authors: Takeuchi Tsutomu , Abe Tohru , Koide Jun , Hosono Osamu , Morimoto Chikao , Homma Mitsuo
Published: February 2007

The cellular mechanism of anti‐DNA antibody synthesis in patients with systemic lupus erythematosus (SLE) was studied by DNA‐specific solid‐phase radioimmunoassay. Anti‐DNA antibody synthesis in response to DNA was T‐dependent, and the experiments with reconstituted lymphocytes from identical twins discordant for SLE showed that B cells and T cells from SLE patients must cooperate to synthesize anti‐DNA antibody. Anti‐DNA antibody synthesis by lymphocytes from patients with inactive SLE was enhanced by T4 cells and suppressed by T8 cells in response to DNA. Although T4 cells from patients with active SLE could enhance anti‐DNA antibody synthesis by autologous B cells, their T8 cells could not suppress anti‐DNA antibody synthesis by autologous B cells. These results indicate that elevated anti‐DNA antibody synthesis in response to DNA in patients with active SLE is due to abnormalities of both SLE B cells and SLE T cells. They further indicate that dysfunction of T8 cells from patients with active SLE may, in part, be responsible for deficient regulation of anti‐DNA antibody synthesis.
Connective tissue activation
Authors: Gordon Michael A. , Hollenberg Morley D. , Castor C. William
Published: February 2007

A protein factor in human urine which has the ability to activate connective tissue cells has been identified and partially purified; it appears to be different from epidermal growth factor and IgG. This urinary connective tissue activating factor (CTAP‐U) is nondialyzable, labile to protease, stable to thiols, heat, and acid, and has an acidic isoelectric point. Purified preparations of CTAP‐U have biologic activities that cause human connective tissue cells to synthesize incremental amounts of 14C‐hyaluronic acid, 35S‐proteoglycans, and 3H‐DNA in vitro. The cell spectrum responsive to this substance includes human synovial cells, human chondrocytes, and skin fibroblasts. CTAP‐U does not react with antisera to connective tissue activating peptide‐III or to antibodies against IgG or its Fc and Fab fragments. Furthermore, CTAP‐U does not cross‐react in a radioreceptor assay for insulin, basic somatomedin, or epidermal growth factor‐urogastrone. Utilizing standardized isolation conditions, CTAP‐U preparations with these properties have been isolated from the urine of 6 normal individuals.
Calcium pyrophosphate crystal deposition
Authors: Mandel Neil S. , Mandel Gretchen S. , Carroll Debra J. , Halverson Paul B.
Published: February 2007

Deposition of crystalline triclinic (t) and monoclinic (m) calcium pyrophosphate dihydrate (CPPD) in fibrocartilage and articular cartilage is the hallmark of chondrocalcinosis. Using biologic grade gelatin to model this crystal growth process, t‐CPPD, m‐CPPD, amorphous calcium pyrophosphate, orthorhombic calcium pyrophosphate tetrahydrate (o‐CPPT), and 3 mixed calcium/sodium pyrophosphate salts were grown at physiologic pH. Amorphous and o‐CPPT appeared to be kinetic precursor crystals in the formation of t‐CPPD and m‐CPPD. Optimal concentration ranges for the different crystals were determined.
Chloroquine inhibits the production of a mononuclear cell factor by inhibition of lectin binding
Authors: Baker Daniel G. , Baumgarten Dottie F. , Dwyer James P.
Published: February 2007

The effect of chloroquine (CQ) on the ability of normal human peripheral blood monocytes to produce a soluble mononuclear cell factor (MCF) capable of stimulating prostaglandins from adherent rheumatoid synovial cells was studied. CQ inhibited concanavalin A (Con A)‐ and bacterial peptidoglycan‐induced MCF activity, but not colchicine‐induced activity, in a dose‐dependent manner. After incubation with CQ for 20 minutes, 3H Con A binding was reduced by 50%, and metabolism of pre‐bound 3H Con A was inhibited. These data suggest that CQ can inhibit MCF production by inhibition of lectin binding, perhaps by inhibition of receptor recycling.
Antibodies to vimentin intermediate filaments in sera from patients with systemic lupus erythematosus
Authors: Alcover Andrés , Molano Jesús , Renart Jaime , Gil‐Aguado Antonio , Nieto Antonio , Avila Jesús
Published: February 2007

Sera from patients with systemic lupus erythe‐matosus and from healthy subjects were tested, using immunofluorescence and blotting techniques, for the presence of antibodies to intermediate filaments of the cytoskeleton of human skin fibroblasts. Both techniques showed that antibodies to intermediate filaments were found in a higher proportion of sera from patients (53%) than healthy subjects (9%). The antigen target was found to be the protein band that corresponded to vimentin (Mr 57,000).
Chondroclasts and osteoclasts at subchondral sites of erosion in the rheumatoid joint
Authors: Bromley Michael , Woolley David E.
Published: February 2007

Histochemical and ultrastructural studies of bone‐cartilage junctions from 21 rheumatoid knee joints have demonstrated the presence of both osteoclasts and chondroclasts. Significant erosions of bone and mineralized cartilage were observed in 15 specimens, and 6 showed localized erosions of unmineralized (hyaline) cartilage. Chondroclasts, defined by their close association with both mineralized and unmineralized cartilage, were morphologically and histochemically similar to osteoclasts. Our observations suggest that these multinucleate cells play a crucial role in subchondral tissue destruction, but that erosion of unmineralized cartilage is primarily the result of synovial pannus tissue.
Sjöugren's syndrome influence of multiple hla‐d region alloantigens on clinical and serologic expression
Authors: Wilson Raymond W. , Provost Thomas T. , Bias Wilma B. , Alexander Elaine L. , Edlow Donald W. , Hochberg Marc C. , Stevens Mary Betty , Arnett Frank C.
Published: February 2007

The relationships of HLA—DR and the newer DS (second D locus) B cell alloantigens (MB and MT) to the clinical and serologic expression of primary and secondary forms of Sjögren's syndrome (SS) were examined in 102 patients (86 whites and 16 blacks). Although HLA‐DR3 was significantly increased in whites (25 of 50, 50%) and blacks (4 of 5, 80%) with primary SS compared with race‐matched normal controls, it was not appreciably elevated in those with systemic lupus erythematosus (SLE)‐SS, rheumatoid arthritis (RA)‐SS, or connective tissue disease‐SS. The MT2 specificity, however, was more strongly associated with primary SS (86% of whites and 100% of blacks) and also with SLE‐SS and RA‐SS compared with race‐matched normal controls. Furthermore, MT2 was significantly increased in SLE‐SS and RA‐SS when compared with non‐sicca SLE and RA controls. Although primary and secondary SS were most strongly associated with this DS specificity (MT2), the anti‐Ro (SS‐A) and anti‐La (SS‐B) antibody responses were more closely allied to DR antigens. HLA‐DR3 was increased in anti‐Ro positive patients, both whites and blacks, with primary SS (74%) and in total anti‐Ro positive subjects (54%) compared with their anti‐Ro negative counterparts (38% and 31%, respectively). Among DR3 negative patients, HLA‐DR2 correlated with anti‐Ro in both primary SS (83%) and in the total SS group (58%). Thus, 96% of Ro antibody positive patients with primary SS had DR3 and/or DR2, as did 80% of anti‐Ro positive subjects in all categories. Antibodies to La (SS‐B) correlated only with DR3 in primary SS and in the total group. These data suggest that MT2 is the strongest major histocompatibility complex determinant for primary and secondary SS. However, HLA‐DR3 and DR2 may mediate the Ro/La antibody responses that are characteristic of more severe disease. The clinical expression of Sjögren's syndrome appears to result from the complex genetic interplay of multiple HLA‐D region factors.
Characterization of a new antigen‐antibody system (su) in patients with systemic lupus erythematosus
Authors: Treadwell Edward L. , Alspaugh Margaret A. , Sharp Gordon C.
Published: February 2007

A new antigen (Su) from calf thymus nuclear extract that reacts with sera from patients with systemic lupus erythematosus (SLE) is described. Antibodies to Su, demonstrated by immunodiffusion, were most frequently found in patients with a diagnosis of probable or definite SLE. Thirty‐seven percent of patients with Su antibodies and a diagnosis of SLE were positive for antinuclear antibodies by indirect immunofluorescence, but lacked specific antibodies previously associated with SLE. Patients with Su antibodies exhibited a higher frequency of Raynaud's phenomenon, but exhibited a lower frequency of malar rash, alopecia, and arthritis when compared with SLE patients in previously published reports. The Su antigen is weakly acidic, heatstable at 37°C, heat‐sensitive at 56°C, resistant to DNase and RNase, but sensitive to trypsin. Its molecular weight approximated 154,000 daltons by Sepharose chromatography. The Su antibody may be associated with a subset of SLE patients with distinct clinical features, and may serve as a serologic marker for patients who are positive for fluorescent antinuclear antibodies but have no other detectable SLE‐associated antibodies.
Cytotoxic anti‐t cell antibodies in children with juvenile rheumatoid arthritis
Authors: Barron Karyl S. , Lewis Dorothy E. , Brewer Earl J. , Marcus Donald M. , Shearer William T.
Published: February 2007

The object of this investigation was to determine the prevalence of anti‐T cell antibodies in 66 children with various connective tissue diseases. Anti‐T cell antibodies were found in 43/44 juvenile rheumatoid arthritis (JRA) patients (mean cytotoxicity 15.0%) and in 10/10 children with systemic lupus erythematosus (mean cytotoxicity 20.0%), but in only 1/15 normal controls and in none of 12 children with other arthritides. There was no significant difference in mean percent cytotoxicity among the JRA subclasses. In the JRA patients, the percent cytotoxicity was positively correlated with the erythrocyte sedimentation rate (P = 0.01), but not with the presence or absence of rheumatoid factor, antinuclear antibodies, or immune complexes. The sera of 3 JRA patients repeatedly inhibited the stimulation of normal lymphocytes by mitogens and antigens by 47–99% (measured by the incorporation of 3H‐thymidine into DNA) when added to the culture system in the first 24 hours; normal sera did not. Sera from patients with JRA have increased reactivity with mitogen‐activated lymphocytes and T cells compared with unstimulated cells as determined by flow cytometry. The expression of the “JRA antigen” requires protein synthesis but not DNA synthesis or cell division. We conclude that the majority of patients with active JRA have cytotoxic anti‐T cell antibodies and that in selected patients, these antibodies may play a role in regulation of the immune response.
Use of the HEp‐2 cell substrate in the detection of antinuclear antibodies in juvenile rheumatoid arthritis
Authors: Osborn Thomas G. , Patel Nirupa J. , Moore Terry L. , Zuckner Jack
Published: February 2007

Presence and titer of antinuclear antibodies (ANA) were determined in 217 juvenile rheumatoid arthritis (JRA) patients, by indirect immunofluorescence using HEp‐2 cells as substrate. Positive ANA titers (⩾1:40) were present in 131 (60%) of the JRA patients. All 3 JRA onset types demonstrated increased percentages of ANA positivity compared with healthy children. Sixty‐seven percent of the patients in the polyarticular onset group had positive titers; titers were positive in 62% of the pauciarticular onset group and in 32% of the systemic onset group. ANA were also found in 45% of control patients with other connective tissue diseases. In JRA patients, the speckled pattern occurred most commonly (72%). Fourteen patients (8 with pauciarticular onset and 6 with polyarticular onset) had iridocyclitis; all of them had high titers (⩾1:80) of ANA. The use of HEp‐2 cells provided a sensitive substrate for detecting ANA in JRA. It proved to be of value in differentiating JRA patients from healthy controls, but not from patients with other connective tissue diseases.
The production of collagenase by adherent mononuclear cells cultured from human peripheral blood
Authors: Louie James S. , Weiss Judy , Ryhänen Lasse , Nies Kenneth M. , Rantala‐Ryhänen Sirpa , Uitto Jouni
Published: February 2007

Mononuclear cells were isolated from human peripheral blood by Ficoll‐Hypaque centrifugation, and the cells adherent to plastic substrata were cultured in serum‐free media supplemented with lactalbumin hydrolysate. These cell cultures, which consisted predominantly of monocyte‐macrophages as judged by nonspecific esterase staining, accumulated collagenase in the medium. This collagenase resembled other vertebrate collagenases in that it cleaved native triple‐helical type I collagen at a locus 3/4‐length away from the amino‐terminal end of the molecule. The collagenase activity was inhibited by Na2EDTA, dithiothreitol, and fetal calf serum, while the addition of Ca++ or N‐ethylmaleimide enhanced the enzyme activity. The accumulation of collagenase in the culture media was markedly enhanced by the incubation of cells with concanavalin A or phorbol myristic acetate. In the presence of cycloheximide, the levels of collagenase activity were markedly reduced, suggesting that active protein synthesis was required to express the enzyme activity. In additional experiments, monocytes were further purified by counterflow centrifugation‐elutriation. The collagenase production was markedly increased in cultures enriched in monocyte‐macrophages and devoid of polymorphonuclear leukocytes. The accumulation of collagenase in monocyte cultures incubated for 48 hours in the presence of concanavalin A or phorbol myristic acetate was of the same order of magnitude as in parallel cultures containing the same number of polymorphonuclear leukocytes purified by Ficoll‐Hypaque centrifugation and Plasmagel sedimentation. The demonstration of collagenase activity in the monocyte cultures appears to reflect the increased diversity of monocyte functions which may play an important role in the tissue damage in chronic inflammatory diseases such as rheumatoid arthritis.
The lupus anticoagulant. A disease marker in antinuclear antibody negative lupus that is cross‐reactive with autoantibodies to double‐stranded DNA
Authors: Colaco C. Bernard , Elkon Keith B.
Published: February 2007

The lupus anticoagulant (LA) was demonstrated in 37% of 52 consecutive systemic lupus erythematosus (SLE) patients and patients with lupus‐like syndromes, who were referred to our unit. The LA was found to be associated with a biologic false‐positive VDRL (P < 0.005), and the apparently paradoxical association of LA with vascular thromboses was confirmed (P < 0.05). The presence of LA and a biologic false‐positive VDRL defined a group of 7 antinuclear antibody negative patients with characteristic features of recurrent thromboses, spontaneous abortions, neurologic involvement, and renal disease. Further studies on 6 selected sera demonstrated LA in all 6 IgM fractions and in 3 of 6 IgG fractions. Inhibition of LA was shown in 6 of 9 Ig fractions after absorption with double‐stranded DNA (dsDNA). Anticardiolipin antibody was shown by immunodiffusion in 3 LA positive IgG fractions from VDRL negative sera. Cardiolipin micelles partially inhibited anti‐dsDNA binding of 4 IgG fractions, 3 of which were LA negative. In this report we discuss the overlapping specificities due to cross‐reactivity between LA, anticardiolipin, and anti‐dsDNA antibodies in human SLE, and we suggest that LA be considered equivalent to the biologic false‐positive VDRL as a criterion for the diagnosis of SLE.
Cartilage nucleoside triphosphate pyrophosphohydrolase. II. role in extracellular pyrophosphate generation and nucleotide metabolism
Authors: Ryan Lawrence M. , Wortmann Robert L. , Karas Barbara , McCarty Daniel J.
Published: February 2007

Extracellular generation of inorganic pyrophosphate (PPi) in cartilage organ culture is markedly augmented by ATP. ATP, not an ATP metabolite (ADP, AMP, adenosine), is necessary for this augmentation. Excess PPi production is effectively blocked by known inhibitors of nucleoside triphosphate (NTP) pyrophosphohydrolase (EDTA, EGTA, dithiothreitol). Excess 32P‐PPi is generated directly from γ32P‐ATP by cartilage, as substrate and product have similar specific activities. These findings strongly favor ecto‐NTP pyrophosphohydrolase as the source of extracellular PPi generation in the presence of NTP. Additionally, active nucleotide and nucleoside catabolism is demonstrated in these cartilage organ cultures.
Blastomycosis presenting as monarticular arthritis. The role of synovial fluid cytology
Authors: George Jr. Alfred L. , Hays J. Taylor , Graham Barney S.
Published: February 2007

Joint complaints are common among patients with blastomycosis; however, true arthritis is infrequently documented by synovial fluid analysis. Of 72 individuals with blastomycosis who were patients at the Vanderbilt School of Medicine affiliated hospitals during the period 1957–1983, 6 (8%) had arthritis at presentation. In 5 patients (7%), monarticular arthritis was the chief complaint leading to hospitalization. Cytologic examination of synovial fluid was performed in 4 patients and demonstrated characteristic organisms each time. Three patients had negative 10% potassium hydroxide smears, and 2 had negative synovial fluid cultures. Blastomycosis should be considered in the differential diagnosis of acute arthritis. In patients with blastomycotic arthritis, cytologic examination of synovial fluid can add to the diagnostic yield of synovial fluid fungal cultures and potassium hydroxide preparations.
Etiopathogenesis of the rheumatoid arthritis–like disease in MRL/1 mice. I. The histomorphologic basis of joint destruction
Authors: O'sullivan Frank X. , Fassbender Hans‐Georg , Gay Steffen , Koopman William J.
Published: February 2007

MRL/1 mice spontaneously develop a hindlimb arthropathy, as well as a number of immunologic abnormalities, including circulating rheumatoid factors. Although previous studies have suggested that this arthropathy is primarily an inflammatory process, we performed a comprehensive histomorphologic study which indicated that inflammation is a late manifestation of MRL/1 arthritis. The pathologic changes that occur in the joints of these mice can be divided into 3 stages. The first stage develops between the ages of 7 and 13 weeks and consists of synovial cell proliferation in the joint recesses. The second stage is characterized by continued proliferation of synovial cells which take on an appearance similar to that of transformed mesenchymal cells. The earliest destructive changes occur in the second stage and include marginal erosions, followed soon after by progressive destruction of articular and meniscal cartilage. The final stage is characterized by a diminution of synovial cell proliferation, extensive cartilage destruction, formation of scar tissue and fibrocartilage, and a very moderate infiltration of the synovial stroma by mononuclear and polymorphonuclear inflammatory cells. Throughout the disease progression there is a striking dissociation between inflammatory cell infiltration or exudation and tissue destruction. The histomorphologic similarities between human rheumatoid synovitis and the arthritis of MRL/1 mice, as well as the presence of rheumatoid factors, make this mouse strain an excellent model for studying human rheumatoid arthritis.
The autologous mixed lymphocyte reaction is decreased in Freund's adjuvant–injected rats of arthritis‐susceptible and ‐insusceptible strains
Authors: Crowe William E. , Crowe William E. , Battisto Jack R. , Smith R. N.
Published: February 2007

We examined the T–non‐T cell autologous mixed lymphocyte reaction (AMLR) of spleen cells from rats with arthritis induced by Freund's complete adjuvant in an effort to establish an animal model for the study of the relationship between the AMLR and autoimmune disease. We found that the splenic T–non‐T AMLR was markedly decreased in rats with adjuvant‐induced arthritis and that this decrease was mediated by suppressor cells within the nylon‐wool–adherent stimulator cell population. However, we also found a similar decrease in the AMLR of arthritis‐resistant Fisher 344 rats that received Freund's complete adjuvant but did not develop arthritis. Control animals with local inflammation induced by turpentine, a nonarthritogenic inflammatory substance, had normal AMLR, whereas other controls given Freund's incomplete adjuvant, also a nonarthritogenic substance, had a modest responder cell–mediated decrease in AMLR. These studies help to clarify the relationship between the decreased AMLR and the pathogenesis of adjuvant‐induced arthritis by demonstrating that: 1 the acute‐phase inflammatory response does not reduce the AMLR; and 2 the decreased AMLR can occur in the absence of overt autoimmune disease. This latter observation calls into question the proposed pathogenetic relationship between the AMLR and autoimmune disease states.
Proteoglycan depletion, rather than fibrillation, determines the effects of salicylate and indomethacin on osteoarthritic cartilage
Authors: Palmoski Marshall J. , Brandt Kenneth D.
Published: February 2007

The effects of salicylate and indomethacin on glycosaminoglycan (GAG) synthesis by atrophic and osteoarthritic (OA) canine cartilage were examined in vitro by transecting distal femora at the metaphysis and incubating the knuckle, with its overlying cap of articular cartilage, in medium containing sodium salicylate or indomethacin, and 35SO4. Atrophic cartilage had an intact articular surface, but its uronic acid content averaged 65% of the control level, and GAG synthesis was decreased to 50% of control values. Both salicylate and indomethacin decreased net GAG synthesis in the atrophic cartilage by an additional 10%. OA cartilage showed surface disruption, a uronic acid content 49% of the control value, and a 49% increase in net GAG synthesis. Salicylate and indomethacin profoundly decreased GAG synthesis in the OA cartilage. However, GAG synthesis and uronic acid content of cartilage which had been lacerated in vitro immediately prior to culture (to stimulate fibrillation) were normal and not affected by either drug. The data emphasize the importance of matrix proteoglycan content in protecting the chondrocyte from the suppressive effects of salicylate and indomethacin on GAG metabolism, and suggest that the lower proteoglycan content of OA cartilage may be more important than fibrillation in rendering it vulnerable to the metabolic effects of these drugs.
The specificity of antibodies to the F(ab′)2 fragment of human IgG
Authors: Heimer Ralph , Wolfe Lawrence D. , Abruzzo John L.
Published: February 2007

The specificity of IgG anti‐F(ab′)2 antibodies was examined in unfractionated sera of patients with rheumatoid arthritis and also with affinity‐purified antibody preparations. Examination of the sera by an enzyme‐linked immunosorbent assay, using pooled human F(ab′)2 fragments absorbed to microtiter plates, revealed that IgG anti‐F(ab′)2 antibodies cross‐react with human and rabbit IgG and rabbit F(ab′)2. IgG anti‐F(ab′)2 antibodies were purified by affinity chromatography and, when tested by a fluid‐phase inhibition enzyme‐linked immunosorbent assay, were found to be of 2 types. One fraction, similar to pepsin agglutinator, reacted with human F(ab′)2 fragment alone. The other fraction was cross‐reactive with human IgG and yet failed to react with idiotopes on Fab or epitopes on Fc fragments. The IgG anti‐F(ab′)2 antibodies we purified had no reactivity toward a human immune complex prepared from tetanus toxoid and antitoxoid.
Collagen synthesis regulation by the aminopropeptide of procollagen i in normal and scleroderma fibroblasts
Authors: Perlish Jerome S. , Timpl Rupert , Fleischmajer Raul
Published: February 2007

The effect of the aminopropeptide of type I procollagen, Col 1(1), on collagen synthesis by normal and scleroderma fibroblasts was investigated. Collagen synthesis was inhibited by about 42% when normal fibroblasts were labeled with 3H‐proline in the presence of 4 μM Col 1(I). In contrast, collagen synthesis by scleroderma fibroblasts was inhibited to a lesser degree, about 19%. Furthermore, scleroderma fibroblasts with elevated rates of collagen synthesis (2.5–5 times normal) were inhibited by only about 10%. The data suggest that the increased accumulation of collagen in the skin of scleroderma patients may be related to a defect in the regulation of collagen synthesis by the aminopropeptide.
The effect of D‐penicillamine on pulmonary findings in systemic sclerosis
Authors: Steen Virginia D. , Owens Gregory R. , Redmond Carol , Medsger Thomas A.
Published: February 2007

D‐penicillamine has been used for the treatment of systemic sclerosis for 2 decades. Forty‐four systemic sclerosis patients who received a mean dose of 636 mg of D‐penicillamine for 2.3 years and 48 untreated patients, who had repeat pulmonary function tests performed after a mean of 3.5 and 4.8 years, respectively, were evaluated. There were no significant changes in the vital capacity or the forced expiratory volumes during this time in either group. However, the diffusing capacity for carbon monoxide improved from 76% of predicted to 87% of predicted in D‐penicillamine‐treated patients. Untreated patients changed slightly, from 73% of predicted to 76% of predicted. When multiple logistic regression analysis was used to account for factors which could have biased treatment comparisons, the improvement related to use of the D‐penicillamine was significant (P < 0.05). This improvement in the D‐penicillamine‐treated patients was associated with no further progression of dyspnea or fibrosis on chest radiograph, as well as reduced skin thickening. These data suggest that D‐penicillamine may be useful in the treatment of systemic sclerosis that involves the lung; however, further studies are needed.
Computed tomography in the diagnosis of early ankylosing spondylitis
Authors: Fam Adel G. , Rubenstein Joel D. , Chin‐Sang Hyacinth , Leung Frances Y. K.
Published: February 2007

Computed tomography (CT) was compared with plain radiography and quantitative sacroiliac (SI) scintigraphy in 28 patients with early ankylosing spondylitis (AS) of ⩽10 years duration. Compared with conventional radiography, CT improved delineation of the SI joints and revealed more abnormalities and higher grades of sacroiliitis; this was significant in patients with early AS of ⩽3 years duration. Quantitative sacroiliac scintigraphy showed higher SI joint:sacrum ratios of radioisotope uptake in patients with AS compared with controls. However, its diagnostic usefulness was limited by the frequency of inconsistent results and the lack of specificity. CT examination of the SI joints may be a useful adjunct in the diagnosis of early AS.
Different defects of T cell regulation of epstein‐barr virus‐induced B cell activation in rheumatoid arthritis
Authors: Kahan Alice , Kahan André , Amor Bernard , Menkes Charles J.
Published: February 2007

Several reports have shown a defective Epstein‐Barr virus (EBV)‐specific suppressor T cell function in rheumatoid arthritis (RA), suggesting that EBV may have a role in the pathogenesis of RA. EBV‐specific T cell regulation was studied in 47 EBV‐immune RA patients and in 14 EBV‐immune control subjects by comparing the secretion of IgM into supernatants of 28‐day cultures of B cells alone and cocultures of B and autologous T cells. In control subjects, autologous T cells mediated a significant decrease in the secretion of IgM by B cells at 12 and 16 days of culture. Analysis of individual responses demonstrated the existence of 3 subgroups of RA patients: group I (18 patients) had a suppressor T cell function similar to that of controls; group II (21 patients) had a defective T cell function; group III (8 patients) was characterized by a “late help phenomenon.” Moreover, in RA group III, IgM secretion in cultures of B cells alone was lower than that seen in controls, RA group I, or RA group II. Differences in the duration or severity of the disease, or in the use of slow‐acting therapeutic agents, corticosteroids, and nonsteroidal antiinflammatory drugs could not account for these subdivisions. Thus, our study demonstrates that several immunoregulatory defects exist in subgroups of RA patients.