bluuebunny/crossref_metadata_2025 huggingface dataset:
The clinical features of elderly‐onset rheumatoid arthritis. A comparison with younger‐onset disease of similar duration
Authors: Deal Chad L. , Meenan Robert F. , Goldenberg Don L. , Anderson Jennifer J. , Sack Burton , Pastan Robert S. , Cohen Alan S.
Published: February 2007

Patients with elderly‐onset rheumatoid arthritis (EORA) may represent a clinical subset of individuals who differ prognostically and therapeutically from patients with younger‐onset disease (YORA). In order to test this hypothesis, we reviewed the records of 212 patients with rheumatoid arthritis and grouped them according to age at onset above or below 60 years old. Seventy‐eight EORA patients and 134 YORA patients with disease duration of ⩽10 years were used for a comparison of presenting features and disease outcome. Abrupt onset occurred somewhat more frequently in EORA, but was not associated with a significantly different clinical course than was an insidious presentation in this older group. There were no differences between the EORA and YORA groups in terms of mean initial joint score, although the scores for the YORA group had wider variation. An initial clinical presentation resembling polymyalgia rheumatica (PMR) was 4 times as frequent in EORA. Elderly patients were less likely to have subcutaneous nodules or rheumatoid factor at disease onset. At the final examination, the EORA patients had lower joint scores and higher health assessments despite similar courses of treatment. These outcome differences persisted when patients with PMR‐like presentations were excluded. Multivariate analyses indicated that joint scores and disease duration made important contributions to a better outcome of EORA, whereas PMR presentation and abrupt onset did not. After an adjustment was made for these 4 features, age at onset was an important contribution to joint score outcome. These results confirm the existence of important differences in onset, clinical features, and prognosis between patients with EORA and those with YORA.
Crystal‐induced endogenous pyrogen production. A further look at gouty inflammation
Authors: Malawista Stephen E. , Duff Gordon W. , Atkins Elisha , Cheung Herman S. , McCarty Daniel J.
Published: February 2007

We found previously that crystals of sodium urate and silicon dioxide (silica) can stimulate the production of endogenous pyrogen (EP), now called interleukin‐1 (IL‐1), the polypeptide mediator of fever and other aspects of inflammation. We have confirmed and extended the work with urate crystals and have examined 2 other crystals associated with joint problems, hydroxyapatite (HA) and calcium pyrophosphate dihydrate (CPPD). The crystals were added to suspensions of human blood leukocytes (2.5 × 106 monocytes/dose, with 10% fresh autologous plasma); after 18 hours of incubation, the EP content of the supernatants was assayed in the rabbit pyrogen test. HA and CPPD crystals neither induced EP production nor reduced the amount of staphylococci‐induced EP. Presized (10‐40 μm) urate crystals were pyrogenic, but less so than the unsized and aggregated urate crystals investigated previously and reexamined here. On ultrasonication, the aggregated urate crystals became first more pyrogenic and then less so as the crystals were dispersed and broken down. Ultrasound did not impart pyrogenicity to HA or CPPD crystals: their failure to stimulate EP/IL‐1 production from leukocytes in vitro indicates a difference in their phlogistic properties, compared with crystals of urate or silica. The results with urate crystals have pathogenetic implications in a number of areas of gouty inflammation: initiation of the acute attack, other aspects of the acute‐phase response, polyarticular involvement, and the inflammatory consequences of chronic stimulation by tophaceous material.
How many joints in the hands and wrists should be included in a score of radiologic abnormalities used to assess rheumatoid arthritis?
Authors: Sharp John T. , Young Donald Y. , Bluhm Gilbert B. , Brook Andrew , Brower Anne C. , Corbett Mary , Decker John L. , Genant Harry K. , Gofton J. Philip , Goodman Neal , Larsen Arvi , Lidsky Martin D. , Pussila Pekka , Weinstein Aaron S. , Weissman Barbara N. , Sharp John T. , Young Donald Y. , Bluhm Gilbert B. , Brook Andrew , Brower Anne C. , Corbett Mary , Decker John L. , Genant Harry K. , Gofton J. Philip , Goodman Neal , Larsen Arvi , Lidsky Martin D. , Pussila Pekka , Weinstein Aaron S. , Weissman Barbara N.
Published: February 2007

Numerous methods for reading abnormalities of rheumatoid arthritis in hand and wrist radiographs have been proposed over the past several decades. There are many differences among these methods, one of the more striking of which is the variation in the number of joints that are scored. In this study, we tested the number of joints that need to be read in order to represent abnormalities accurately and reproducibly, using the scores of multiple observers. Thirteen rheumatologists and radiologists each read a set of 41 hand and wrist films from patients with rheumatoid arthritis. Ten of 13 readers scored 27 joints in each hand and wrist; the other 3 readers scored fewer areas. Fourteen combinations of joints were selected based on the frequency of involvement and the technical adequacy of routine films in assessing a given area. After testing these 14 different combinations, 1 scheme, which included 17 areas read for erosions and 18 areas read for joint space narrowing, was tested further. The correlation coefficients for 10 intraobserver scores derived from this modified scheme compared with the original scores were between 0.981 and 0.997. Seventy‐one of 78 interobserver comparisons were better using the new scheme than using the original scheme. These data indicate that the simplified scheme, using a combination of 17 joints to score erosions and 18 to score joint space narrowing, more accurately reflects the extent of abnormalities perceived by a panel of experts than does the original scheme. This abbreviated number of joints shortens the amount of time required to read a set of films and simplifies the scoring of films, since a number of areas that are difficult to read are eliminated from radiographic assessment.
Cancer and systemic sclerosis. An epidemiologic study
Authors: Roumm Alan D. , Medsger Thomas A.
Published: February 2007

The association between systemic sclerosis and malignancy was evaluated in the Pittsburgh standard metropolitan statistical area during 1971–1982 and compared with data for this geographic area from the Third National Cancer Survey of 1969‐1971. Fourteen malignancies were detected in 262 systemic sclerosis patients (5%) during a followup period that included 1, 335 patient‐years. After adjustment for age and sex, the expected number of malignancies was 7.72 (relative difference = 1.81; P = 0.05). This increased relative difference was predominantly due to an increase in observed lung cancer (relative difference = 4.4; P < 0.05), which occurred in the setting of long‐standing pulmonary fibrosis but was not associated with cigarette smoking. Although breast cancer was no more frequent than expected, it tended to occur in close temporal relationship with the onset of systemic sclerosis. These findings suggest a biologic relationship between systemic sclerosis and certain malignant neoplasms.
Peripheral inflammatory vascular disease in Sjögren's syndrome. Association with nervous system complications
Authors: Molina R. , Provost T. T. , Alexander E. L.
Published: February 2007

Two histopathologic types of inflammatory vascular disease (IVD) occur in Sjögren's syndrome (SS): mononuclear IVD (MIVD) and neutrophilic IVD (NIVD). We describe 50 SS patients with IVD (30 with NIVD and 20 with MIVD). Thirty‐three (66%) of the SS patients with biopsy‐documented IVD had nervous system disease unattributable to other causes. Nineteen patients (58%) had involvement of both the central and peripheral nervous systems, while 9 had peripheral and 5 had central nervous system dysfunction alone. Patients with both histopathologic types of IVD were at risk for the development of nervous system abnormalities (57% of NIVD patients and 80% of MIVD patients). Indirect evidence is presented which suggests that IVD may play a role in the immunopathogenesis of nervous system disease, at least in a subset of SS patients.
Seronegative polyarthritis in giant cell arteritis
Authors: Ginsburg William W. , Cohen Marc D. , Hall Stephen B. , Vollertsen Randall S. , Hunder Gene G.
Published: February 2007

Nineteen of 520 patients with biopsy‐proven giant cell arteritis were found to have persistent seronegative, symmetric polyarthritis with a mean joint count of 20 (swollen plus tender). In 9 patients in the onset of polyarthritis occurred prior to the diagnosis of giant cell arteritis, 3 had simultaneous onset, and 7 developed polyarthritis within 3 years after the onset of giant cell arteritis. Ten of the 19 patients demonstrated radiographic features of joint space narrowing and/or erosions. In 1 patient in a synovial biopsy was performed, revealing marked multinucleated giant cell infiltration. A persistent seronegative polyarthritis, although uncommon in giant cell arteritis, may be its presenting symptom. Other symptoms of giant cell arteritis should be sought in patients who exhibit this feature, especially in those whose arthritis begins at age 50 or older.
Distal interphalangeal joint involvement in rheumatoid arthritis
Authors: Jacob Janel , Sartoris David , Kursunoglu Sevil , Pate Deborah , Pineda Carlos J. , Braun Richard M. , Resnick Donald , Weisman Michael H.
Published: February 2007

Sixty‐two patients with seropositive rheumatoid arthritis (RA) were evaluated radiographically for distal interphalangeal (DIP) joint involvement and were compared with 50 age‐ and sex‐matched control subjects. The frequency of DIP erosions was 37% in the patients versus 14% in the controls; these erosions were mild and were not related to disease duration. Erosions elsewhere in the hand and wrist were of all degrees of severity and were related in part to disease duration. Osteophytes occurred frequently in both the RA group (71 %) and the control group (60%). However, joint space narrowing occurred more frequently in RA patients (77%) than in the controls (46%) (P < 0.009). The findings from this study suggest that in RA patients, DIP erosions occur frequently, do not occur in isolation, and are not simply a marker for severe global erosive disease in the hand and wrist. The high frequency of osteophytosis and joint space narrowing in both groups probably represents the overlap of osteoarthritis and RA that occurs in many patients.
Lymphoid irradiation in intractable rheumatoid arthritis. A double‐blind, randomized study comparing 750‐rad treatment with 2,000‐rad treatment
Authors: Hanly John G. , Hassan Jaythoon , Moriarty Michael , Barry Ciaran , Molony Jack , Casey Eoin , Whelan Alex , Feighery Conleth , Bresnihan Barry
Published: February 2007

Twenty patients with intractable rheumatoid arthritis were treated with 750‐rad or 2,000‐rad lymphoid irradiation in a randomized double‐blind comparative study. Over a 12‐month followup period, there was a significant improvement in 4 of 7 and 6 of 7 standard parameters of disease activity following treatment with 750 rads and 2,000 rads, respectively. Transient, short‐term toxicity was less frequent with the lower dose. In both groups, there was a sustained peripheral blood lymphopenia, a selective depletion of T helper (Leu‐3a+) lymphocytes, and reduced in vitro mitogen responses. These changes did not occur, however, in synovial fluid. These results suggest that 750‐rad lymphoid irradiation is as effective as, but less toxic than, that with 2,000 rads in the management of patients with intractable rheumatoid arthritis.
Alterations in macrophage collagenase secretion induced by gold sodium thiomalate
Authors: Spalding David M. , Darby Walter L. , Heck Louis W.
Published: February 2007

The effects of gold sodium thiomalate (GST) on the production of specific collagenase by thioglycolateelicited macrophages was investigated. Our studies demonstrated that GST administration can significantly decrease collagenase production in a dose‐dependent manner. These effects were observed with levels of GST attainable in serum or synovial tissue during routine chrysotherapy. In addition, GST altered lysozyme secretion by activated macrophages in a pattern distinct from that of collagenase alteration. These effects of enzyme secretion were not secondary effects of GST on viability, general protein secretion, or the specific assay procedures utilized, and were not attributable to the thiomalate moiety. Thus, GST may exert its therapeutic effect in rheumatoid arthritis through interference with the production of degradative proteolytic enzymes, which are important effector molecules mediating tissue destruction.
Treatment of rheumatoid synovitis of the knee with intraarticular injection of dysprosium 165‐ferric hydroxide macroaggregates
Authors: Sledge Clement B. , Zuckerman Joseph D. , Zalutsky Michael R. , Atcher Robert W. , Shortkroff Sonya , Lionberger David R. , Rose Howard A. , Hurson Brian J. , Lankenner Peter A. , Anderson Ronald J. , Bloomer William A.
Published: February 2007

One hundred eight knees of 93 patients with seropositive rheumatoid arthritis and persistent synovitis of the knee were treated with an intraarticular injection of 270 mCi of dysprosium 165 bound to ferric hydroxide macroaggregate. Leakage of radioactivity from the injected joint was minimal. Mean leakage to the venous blood 3 hours after injection was 0.11% of the injected dose; this corresponds to a mean whole body dose of 0.2 rads. Mean leakage to the liver 24 hours after injection was 0.64% of the injected dose; this corresponds to a mean liver dose of 3.2 rads. In 7 additional patients examined, there was negligible or near negligible activity found in the draining inguinal lymph nodes. One‐year followup was possible for 74 knees (63 patients). Sixty‐one percent of the knees had good results, 23% had fair results, and 16% had poor results. There was a direct correlation between the radiographic stage and response to treatment. In knees with stage I radiographic changes, 72% showed good results; 93% showed improvement. In knees with stage II changes, 59% showed good results; 81% showed improvement. These preliminary results indicate that dysprosium 165‐ferric hydroxide macroaggregate is an effective agent for radiation synovectomy. The low leakage rates observed offer a definite advantage over agents previously used.
Collagen antibodies in rheumatoid arthritis. SIgnificance of antibodies to denatured collagen and their association with HLA‐DR4
Authors: Rowley Merrill , Tait Brian , Mackay Ian R. , Cunningham Tim , Phillips Brian
Published: February 2007

The frequency, specificity, and HLA associations of antibodies to collagen were examined in 54 patients with severe rheumatoid arthritis (RA) and in 67 control subjects, using native and denatured bovine type II collagen as reactants in a solid‐phase radioimmunoassay. Reactivity to denatured collagen was significantly higher in the RA patients than in the controls (P = 0.004). Reactivity to native collagen was substantially lower than reactivity to denatured collagen and was similar in RA patients and controls. DR4 positive RA patients had significantly greater reactivity to denatured collagen compared with DR4 negative RA patients (P = 0.03), but levels of antibody to native collagen were similar among DR4 positive and DR4 negative patients. These data lend support to the idea that denatured collagen is an important secondary reactant in immunemediated perpetuation of RA.
Nailfold capillary microscopy in mixed connective tissue disease. Comparison with systemic sclerosis and systemic lupus erythematosus
Authors: Granier Françoise , Vayssairat Michel , Priollet Pascal , Housset Edward
Published: February 2007

Nailfold capillary microscopy patterns in 22 patients with mixed connective tissue disease (MCTD) were compared with those of 21 patients with systemic lupus erythematosus (SLE) and 30 patients with systemic sclerosis (scleroderma [SD]). Microvascular data were classified blindly as follows: normal, nonspecific abnormalities, SD pattern, and SLE pattern, with special attention to the presence of dystrophic, branched “bushy” capillary formations. Of the 22 patients with MCTD, 63.6% had an SD pattern, 22.7% had an SLE pattern, 13.6% had nonspecific abnormalities, and 72.7% had bushy capillary formations. Compared with SLE microangiopathy, MCTD microangiopathy exhibited significantly greater capillary loss (P < 0.05), more frequent SD patterns (P < 0.001), and more frequent bushy capillaries (P < 0.001). Compared with SD patients, MCTD patients displayed less frequent SD patterns (P < 0.02) and more frequent bushy capillary formations (P < 0.01). The presence of bushy capillaries was suggestive of MCTD. For diagnostic purposes, bushy capillaries displayed 72% sensitivity, 80% specificity, and 87.2% negative predictive value. The quantitative and qualitative expressions of microangiopathy were different in MCTD and SLE, respectively. This supports the hypothesis that each disease is a distinct entity. Nevertheless, there were many resemblances between MCTD and SD, which implies that MCTD is possibly a clinical form of SD.
Abnormal B cell function in patients with Behçet's disease
Authors: Suzuki Noboru , Sakane Tsuyoshi , Ueda Yuji , Tsunematsu Tokugoro
Published: February 2007

We evaluated B lymphocyte function in 23 patients with Behçet's disease at various stages. The patients with active disease, but not those with inactive disease, were found to have elevated numbers of cells spontaneously secreting immunoglobulin and a decreased B cell response to the T cell‐independent B cell mitogen, Staphylococcus aureus Cowan 1. Moreover, B cells from almost all patients with Behçet's disease were unresponsive to the T cell‐dependent polyclonal activator, pokeweed mitogen. These results indicate that B cell abnormalities, including some which are associated with disease activity, could be involved in the pathogenesis of Behçet's disease.
Infectious arthritis in renal transplant patients
Authors: Bomalaski John S. , Williamson Paul K. , Goldstein Carl S.
Published: February 2007

Infectious complications in the renal transplant patient are common, and infecting agents include opportunistic organisms as well as common pathogens. However, we were only able to document 6 patients who had septic arthritis from more than 800 who received a renal transplant at our institution over an 18‐year period. Furthermore, only 16 other cases of infectious arthritis have been reported in the literature. All of our patients had an apparent predisposing factor and 3 patients had prior infection with the same organism. The knee was the most commonly infected joint. The initial synovial fluid white blood cell count was usually > 30,000 cells/mm3, but 1 patient with viral arthritis initially had noninflammatory fluid. The peripheral blood white blood cell count may not be elevated. All of our cases of initial joint infection occurred by 18 months posttransplant. Blood cultures were positive in 3 of 4 patients with bacterial infection. Followup of these 6 patients averaged 4.3 years. Numerous other rheumatologic syndromes and disorders peculiar to the posttransplant period may mimic a septic joint. Consequently, despite the low frequency of occurrence of septic arthritis, persistent attention to the locomotor system in the transplant patient is warranted.
Enhanced phospholipase activity in peripheral blood monocytes from patients with rheumatoid arthritis
Authors: Bomalaski John S. , Clark Mike A. , Zurier Robert B.
Published: February 2007

Peripheral blood monocytes (PBM) from patients with rheumatoid arthritis (RA) produce greater amounts of prostaglandins (PG) than do control cells. To further explore the reasons for the increased PG production, we assessed the phospholipase activities in these cells. We found that PBM from patients with severe RA expressed greater phospholipase A2 (PLA2) and phospholipase C (PLC) activities than did the control cells. Enhanced PLA2 activities were observed in RA patient cells when phosphatidylcholine (PC) or phosphatidylethanolamine (PE) were used as substrates. Enhanced PLC activities also were seen when PC, PE, and phosphatidylinositol (PI) were used as labeled substrates. Increased PLC activity was observed whether linoleic acid or arachidonic acid was esterified to the 2 position of the phospholipid substrate used. Because all patients with RA were treated with nonsteroidai antiinflammatory drugs, we examined the effects of aspirin ingestion on phospholipase activities. Aspirin had no consistent effect on PLA2 activities but markedly inhibited PLC activities against PC, PI, and PE with arachidonic acid in the R2 position. That aspirin enhanced PLC activities against PC and PI with linoleic acid in the R2 position, suggests that PLC activity may be regulated in part by the R2 fatty acid. Our results indicate that increased phospholipase activities exhibited by PBM from RA patients may help explain the increased PG production by these cells. The increased phospholipase activities in PBM from RA patients do not appear to be due solely to nonsteroidal antiinflammatory drug therapy.
α2‐macroglobulin‐proteinase complexes as correlated with α1‐proteinase inhibitor‐elastase complexes in synovial fluids of rheumatoid arthritis patients
Authors: Borth Wolfgang , Dunky Attila , Kleesiek Knut
Published: February 2007

The levels of α1‐proteinase inhibitor‐elastase and α2‐macroglobulin (α2M)‐proteinase complexes were measured in synovial fluids from arthritis patients by use of specific immunosorbent assays. Both types of proteinase inhibitor‐proteinase complexes were significantly correlated with each other as well as with the total neutrophil count in synovial fluids of rheumatoid arthritis patients but were discordant in synovial fluids of patients with osteoarthritis. One synovial fluid sample showed active (inhibitory) α2M as well as active collagenase. We purified α2M from pooled synovial fluids obtained from patients with rheumatoid arthritis. This α2M retained approximately 90% of its proteinase binding (inhibiting) capacity, compared with that of normal plasma α2M. We found no evidence that α2M was inactivated by means other than proteinases.
Anti‐HLA–B27 antibodies in sera from patients with gram‐negative bacterial infections
Authors: Cavender Druie , Ziff Morris
Published: February 2007

Several forms of seronegative polyarthritis are strongly associated with HLA‐B27, and a number of microorganisms have been implicated in the etiology of these diseases. To explain the association between HLA‐B27 and arthritis initiated by infection with these organisms, it has been proposed that there is immunologic cross‐reactivity between the B27 molecule and 1 or more microbial antigens, and that this cross‐reactivity leads to tolerance to such infection and/or to the production of anti‐HLA‐B27 cross‐reactive antibodies. Such cross‐reactive antibodies were detected in the sera of only 2 of 63 patients recently infected with Shigella flexneri, Campylobacter jejuni, or Yersinia enterocolitica who had highly significant antibody levels against the infecting bacterial species. Most striking was the absence of anti‐HLA‐B27 antibody in the serum of 16 of 17 patients who developed reactive arthritis following Yersinia infection.
Further evidence for the lack of association between acetylator phenotype and systemic lupus erythematosus
Authors: Baer Alan N. , Woosley Raymond L. , Pincus Theodore
Published: February 2007

An association between host acetylator phenotype and idiopathic systemic lupus erythematosus (SLE) has been sought for over a decade, without a definitive result. We have observed that the frequency of the slow acetylator phenotype was similar in 64 patients with idiopathic SLE (38%), 60 healthy volunteers (50%), and 52 non‐SLE medical service patients (44%). The slow acetylator phenotype was not more frequent among subgroups of the SLE patients defined by demographic features or specific manifestations of disease. Our results, as well as a majority of previously published results, do not provide evidence for an association between acetylator phenotype and idiopathic SLE.
Interstitial lung disease in scleroderma. Immune complexes in sera and bronchoalveolar lavage fluid
Authors: Silver Richard M. , Metcalf John F. , LeRoy E. Carwile
Published: February 2007

Interstitial lung disease is a common feature of scleroderma (systemic sclerosis), and it may be a major determinant of morbidity and mortality. Analysis of bronchoalveolar lavage fluid from patients with scleroderma has shown evidence of inflammation in the lower respiratory tract of many patients. We have analyzed sera and bronchoalveolar lavage fluid from scleroderma patients for the presence of immune complexes, which may play a role in the inflammatory process. Using a solid‐phase C1q enzyme‐linked immunosorbent assay, we detected immune complexes in the sera of 6 of 23 patients (26%) and in none of 32 controls (P < 0.01). All 6 patients with serum immune complexes had inflammatory cells in bronchoalveolar lavage fluid, and the presence of serum immune complexes correlated with the percentage of neutrophils in lavage fluid (P < 0.02). Immune complexes were detected in lavage fluid of 11 of 21 patients (52%) compared with 1 of 7 normal controls (14%). Subjects having immune complexes in lavage fluid had a lower forced vital capacity than did those without lavage fluid immune complexes (P < 0.05). The levels of immune complexes in bronchoalveolar lavage fluid exceeded those in serum by a mean of 45‐fold, suggesting either local formation or selective deposition of immune complexes in the lower respiratory tract of some scleroderma patients.
Necrotizing systemic vasculitis with features of both Wegener's granulomatosis and Churg‐Strauss vasculitis
Authors: Henochowicz Stuart , Eggensperger Diane , Pierce Leslie , Barth Werner F.
Published: February 2007

We describe a patient who had nasal biopsy‐demonstrated eosinophilic vasculitis and renal biopsy‐demonstrated necrotizing glomerulonephritis with tissue eosinophilia. Despite corticosteroid therapy, the patient's renal function deteriorated, and nodular pulmonary infiltrates developed. Both conditions responded dramatically when cyclophosphamide was added to the treatment regimen. The renal disease activity was monitored with the aid of cytodiagnostic urinalysis, a technique of limited, albeit well‐established, validity in monitoring renal allograft patients for signs of tissue rejection. This technique provided an improved, semi‐quantitative method for examining urine sediment and, in this patient, was helpful as a measure of renal disease activity.
A multicenter study of hospitalization in rheumatoid arthritis. Frequency, medical‐surgical admissions, and charges
Authors: Wolfe Frederick , Kleinheksel Sue M. , Spitz Patricia W. , Lubeck Deborah P. , Fries James F. , Young Donald Y. , Mitchell Donald , Roth Sanford
Published: February 2007

During 1981, 123 of 816 patients (15.1%) with rheumatoid arthritis were hospitalized 160 times because of the disease. The mean length of hospitalization was 13.1 days, and the cost $7,845. Surgery accounted for 54.4% of admissions, but 69.2% of costs. The average cost for total joint surgery was $12,287. Most medical admissions (46.6%) were for the diagnosis or treatment of articular disease, but 42.5% were for treatment of side effects of therapy, and 11.0% for complications of RA. The most commonly performed surgical procedures included reconstructive surgery of the hand/wrist (n = 35) and foot (n = 22), followed by total knee replacement (n = 18).
Flare of antigen‐induced arthritis in mice after intravenous challenge. Kinetics of antigen in the circulation and localization of antigen in the arthritic and noninflamed joint
Authors: Lens Jan Willem , van den Berg Wim B. , van de Putte Levinus B. A. , Zwarts Wil A.
Published: February 2007

Intravenous injection of methylated bovine serum albumin (mBSA) in mice with unilateral, chronic, mBSA‐induced arthritis has been shown to cause a flare of smouldering arthritis without affecting the contralateral, noninflamed knee joint. We studied the kinetics of 125I‐labeled mBSA in the blood, and the accumulation of antigen in both arthritic and noninflamed joints. The bulk of the antigen was eliminated from the blood within 10–30 minutes, and accumulation of antigen in the joints occurred mainly within this period. The amounts of antigen found in the arthritic joints were of the same order of magnitude as the amounts found in noninflamed joints. Autoradiography of whole joint sections revealed that, in arthritic joints, antigen was located primarily at the deep capillaries and large vessels, and in the noninflamed joints, antigen was located at the small superficial capillaries. Antigen was handled by granulocytes in the arthritic joint and by synovial lining cells in the noninflamed joint. Our data indicate that tiny amounts of antigen reach the synovial stroma in both normal and arthritic joints but cause inflammation only in the arthritic joints, because of local hyper‐reactivity.
Characterization of an expanded subpopulation of large granular lymphocytes in a patient with rheumatoid arthritis
Authors: Combe Bernard , Andary Monique , Caraux Jean , Baldet Pierre , Barchechath Françoise , Clot Jacques , Sany Jacques
Published: February 2007

We describe a rheumatoid arthritis patient who was found to have chronic T cell lymphocytosis and neutropenia. She had an increased number of lymphocytes in the peripheral blood, bone marrow, and liver, and the expanded lymphocyte subset consisted of large granular lymphocytes with a homogeneous phenotype. Of the previously described patients with these large granular lymphocytes, almost one‐fourth have had rheumatoid arthritis.
Binding of normal human mononuclear cells to blood vessels in rheumatoid arthritis synovial membrane
Authors: Oppenheimer‐Marks Nancy , Ziff Morris
Published: February 2007

We examined the binding of mononuclear cells to blood vessels in the rheumatoid arthritis synovial membrane. Two of 4 synovia that had lymphocyte‐rich areas contained blood vessels adhesive for mononuclear cells. These reactive vessels showed striking similarities to high endothelial venules of the paracortical region of lymph node, where normal lymphocyte‐endothelial cell adhesion and lymphocyte emigration into tissue occurs.
Association of cerebrospinal fluid IgM index with central nervous system involvement in Behçet's disease
Authors: Hirohata Shunsei , Takeuchi Akiteru , Miyamoto Terumasa
Published: February 2007

Immunoglobulin (IgM, IgA, and IgG) and albumin values were determined in 12 patients who had signs and symptoms of central nervous system involvement attributable to Behçet's disease. Only the cerebrospinal fluid IgM index, which was significantly elevated in patients with active neuro‐Behçet's syndrome, was found to decrease when the neurologic manifestations of the disease had disappeared. This indicates that determination of this index may be of help in the evaluation of central nervous system disease activity in neuro‐Behçet's syndrome.
Phosphoribosylpyrophosphate synthetase superactivity: A study of five patients with catalytic defects in the enzyme
Authors: Becker Michael A. , Losman Michele J. , Rosenberg Alan L. , Mehlman Ira , Levinson Dennis J. , Holmes Edward W.
Published: February 2007

Superactive phosphoribosylpyrophosphate (PRPP) synthetases were characterized in fibroblasts and erythrocytes from 5 unrelated men with gout and/or hyperuricemia and uric acid overproduction. The kinetic basis of enzyme superactivity in all patients was increased maximal reaction velocity. Affinities of the enzymes for substrates and activators and responsiveness to inhibitors were normal, and levels of immunoreactive enzyme in patient and control fibroblast and erythrocyte extracts were comparable. Enzymes purified to homogeneity from 2 patients confirmed the presence of isolated catalytic defects. Altered physical properties of certain of the superactive enzymes suggested the presence of several distinctive structural defects among the aberrant forms. Fibroblasts from each affected patient showed increased PRPP concentration and generation, as well as accelerated rates of all PRPP‐requiring purine nucleotide synthetic pathways. These findings support the concept that enzyme superactivity results in uric acid overproduction as a consequence of increased rates of PRPP and purine nucleotide synthesis. Cultured cells from female relatives of 2 patients showed evidence for the heterozygous carrier state, as measured both by enzyme activities and by rates of PRPP and purine synthesis. The clinical phenotype in 4 patients was limited to early adult‐onset gout and its consequences, whereas the fifth patient expressed a familial constellation of hyperuricemia, sensorineural deafness, ataxia, and renal insufficiency. The severity of the derangements in PRPP synthetase and in PRPP and purine synthesis in cells from the 5 patients, however, was comparable. The neurologic accompaniments of enzyme superactivity found in 1 family described here, and in 2 others described previously, thus may not necessarily be consequences of primary defects in PRPP synthetase.
The neurotoxic effect of gold sodium thiomalate on the peripheral nerves of the rat: Insights into the antiinflammatory actions of gold therapy
Authors: Levine Jon D. , Goldstine Joshua , Mayes Margaret , Moskowitz Michael A. , Basbaum Allan I.
Published: February 2007

Although gold is one of the few therapeutic agents that has been proven effective in producing remission in patients with rheumatoid arthritis, its mechanism of action is unknown. Since nociceptive afferent and sympathetic efferent fibers of the peripheral nervous system contribute to the pathophysiology of inflammation, and since a known side effect of gold therapy is a polyneuropathy, we tested the hypothesis that gold is toxic to small‐diameter peripheral nerve fibers in the rat. We found that prolonged treatment with gold, at the same dosage reported to be effective against adjuvant‐induced arthritis in the rat, produced a significant decrease in the numbers of unmyelinated, but not of myelinated, axons. Gold treatment also elevated nociceptive thresholds in both articular and nonarticular structures. These results suggest that gold produces an antiinflammatory effect on arthritis by a neurotoxic effect on the peripheral nerves involved in neurogenic inflammation.
Urinary neopterin reflects clinical activity in patients with rheumatoid arthritis
Authors: Reibnegger Gilbert , Egg Dietmar , Fuchs Dietmar , Günther Robert , Hausen Arno , Werner Ernst R. , Wachter Helmut
Published: February 2007

Neopterin is a marker for activation of cellular immunity. Urinary neopterin levels were measured in 106 patients with rheumatoid arthritis (RA) and in 45 patients with osteoarthritis. Levels were significantly higher in RA patients than in osteoarthritis patients and were strongly dependent on stage and activity of RA. Correlations with other laboratory parameters were weak. Multivariate analysis demonstrated that urinary neopterin levels reflected clinical activity better than did other laboratory findings. Thus, urinary neopterin determination might be useful in monitoring RA patients.
Production of a glycosaminoglycan stimulatory factor by cloned human t lymphocytes activated in vitro
Authors: Tsao Min , Zeevi Adriana , Whiteside Theresa L.
Published: February 2007

Supernatants of mitogen‐activated mononuclear cells contain a factor which stimulates, up to fifteenfold, the synthesis of glycosaminoglycan (GAG) by cultured normal dermal fibroblasts. To demonstrate that the GAG stimulatory factor is a product of T lymphocytes, we cloned normal peripheral blood T lymphocytes that were activated in mixed lymphocyte culture. Selected alloreactive T cell clones were expanded in the presence of original stimulator cells and T cell growth factor. Only supernatants of the clones that were reactivated with irradiated stimulators (allogeneic peripheral blood lymphocytes of B cell lines) were capable of increasing, 3–7‐fold, the GAG synthesis by dermal fibroblasts. The production of GAG stimulatory activity by alloreactive T cells was restricted by HLA‐DR allorecognition. Alloactivated T cell clones produced more GAG stimulatory activity on a per cell basis than did concanavalin A‐activated mononuclear cells. These results show that cloned, activated T lymphocytes are capable of releasing soluble factors that modulate GAG synthesis by normal dermal fibroblasts.
Murine type II collagen arthritis: Association of an acute‐phase response with clinical course
Authors: Bliven Marcia L. , Wooley Paul H. , Pepys Mark B. , Otterness Ivan G.
Published: February 2007

The acute‐phase reactant, C‐reactive protein, is a good index of disease activity in patients with rheumatoid arthritis. We examined the murine acute‐phase reactant, serum amyloid P, as an index of disease in type II collagen‐induced arthritis in 3 mouse strains. The onset of type II collagen‐induced arthritis, which is characterized by paw swelling, is associated with a significant, but transient, elevation of serum amyloid P. Anticollagen antibody titers are not temporally associated with the onset of disease. Although murine type II collagen arthritis fails to show the chronic acute‐phase reactant elevation that is characteristic of arthritis in humans, the transient elevation of the acute‐phase reactant is a reliable indicator of the onset of disease.
Heterogeneity of proteoglycans extracted before and after collagenase treatment of human articular cartilage: II. Variations in composition with age and tissue source
Authors: Kuijer Roel , Van De Stadt Rob J. , Van Kampen G. P. Jos , De Koning Margret H. M. T. , Van De Voorde‐Vissers Els , Van Der Korst Jan K.
Published: February 2007

Proteoglycans (A1 fractions) were extracted with 4M guanidine hydrochloride (GuHCl) from human articular cartilage samples of a wide age range. Distinctions were made between hip and knee, and upper and lower layers. The residues of these extractions were digested with purified collagenase, and a second extraction with 4M GuHCl was performed, which yielded appreciable amounts of proteoglycans. When pro‐teoglycans from second extractions were compared with those from first extractions, the following changes were observed: an increase in chondroitin sulfate; a relative decrease in keratan sulfate; a decrease in protein content; and a decrease in the ratio of chondroitin 6‐sulfate to chondroitin 4‐sulfate. The same changes were found when nonaggregating proteoglycans were compared with proteoglycan aggregates, when proteoglycans from young cartilage were compared with those from mature cartilage, when proteoglycans from knee cartilage were compared with those from hip cartilage, and when proteoglycans from upper layers of cartilage were compared with those from deeper layers. It is suggested that the differences found between first and second extractions of cartilage, between upper and lower layers of cartilage, and between knee and hip cartilage are caused by variations in the relative amount of nonaggregating proteoglycans and/or variations in proteoglycan size.
Unusual metacarpophalangeal osteoarthritis in a jackhammer operator
Authors: Fam Adel G. , Kolin Arnost
Published: February 2007

Severe, atypical osteoarthritis of the metacarpo‐phalangeal and elbow joints in a jackhammer operator is reported. Articular tissue resected at surgery demonstrated gross fibrillation and histologic evidence of calcification of articular cartilage, and multiple, bony fragments embedded in the synovium. Operation of a pneumatic drill may accentuate a tendency toward development of osteoarthritis in workers who are predisposed to the disease and may also cause it to localize at unusual sites such as the elbow, shoulder, wrist, and metacarpophalangeal joints.
CHARACTERIZATION OF RABBIT GENES FOR SYNOVIAL CELL COLLAGENASE
Authors: Fini M. Elizabeth , Gross Robert H. , Brinckerhoff Constance E.
Published: February 2007

To provide tools for understanding collagenase gene expression in rheumatoid arthritis, we have isolated and characterized genomic clones for rabbit synovial cell collagenase. These clones represent 2 types of collagenase gene, at least 1 of which is transcribed in synovial fibroblasts. By examining the rabbit genome in situ, we provide evidence that there are only 2 different synovial cell collagenase genes found in a haploid genome. Amplification of these genes is not a mechanism for collagenase messenger RNA induction by phorbol esters.
IN vitro production of autoantibodies to u1 ribonucleoproteins by peripheral blood mononuclear cells from patients with connective tissue diseases
Authors: Ohosone Yasuo , Akizuki Masashi , Hirakata Michito , Satoh Minoru , Yamagata Hajime , Homma Mitsuo
Published: February 2007

Antibodies to U1 ribonucleoproteins produced by peripheral blood mononuclear cells from patients with connective tissue diseases were measured by a sensitive enzyme‐linked immunosorbent assay and by immunoblotting. Mononuclear cells from patients with high‐titer serum antibodies spontaneously started secreting IgG anti—U1 RNP antibodies on the second day after culture. The amount of anti—U1 RNP in the culture supernatants reached maximum level on day 8. The most effective production of anti—U1 RNP by B cells was observed when they were cultured in the presence of T cells and adherent cells. Mononuclear cells from patients without anti—U1 RNP antibodies or from normal subjects did not produce a measurable amount of anti—U1 RNP. Treatment of mononuclear cells by cycloheximide resulted in complete inhibition of anti—U1 RNP secretion, which indicates that antibody in the culture supernatants reflects the active biologic phenomenon in vitro. The methods described should be useful in the study of the cellular mechanisms involved in antinu‐clear antibody production of connective tissue diseases.
Human synovial fibroblasts produce urokinase‐type plasminogen activator
Authors: Medcalf Robert L. , Hamilton John A.
Published: February 2007

The plasminogen activator produced by cultured human synovial fibroblasts was investigated both biochemically and immunologically. Stimulated either by all‐trans‐retinoic acid or by monocyte‐conditioned medium, these fibroblasts elaborated a plasminogen activator with electrophoretic mobility similar to that of urokinase (Mr = 52 kilodaltons), and which also had immunologic cross‐reactivity with urokinase. The plasminogen activator found in rheumatoid synovial fluids has been shown to be of the urokinase type. The findings reported here are consistent with the notion that synovial fibroblasts are a source of this proteinase.
Abnormal immunoglobulin and rheumatoid factor synthesis by blood lymphocytes in patients with primary Sjögren's syndrome
Authors: Rodriguez Martjn A. , Baroja Miren L. , Leon‐Ponte Matilde , Abadi Isaac
Published: February 2007

Peripheral blood B lymphocytes from patients with primary Sjögren's syndrome showed significantly higher spontaneous synthesis of IgG, IgM, and IgM rheumatoid factor in vitro, compared with B lymphocytes from healthy controls. Lymphocytes from patients also showed higher IgM rheumatoid factor production after mitogen stimulation. Patients had competent suppressor activity for IgG, but not for IgM synthesis. Pre‐irradiation of T cells, but not depletion of OKT8+ cells, markedly enhanced IgG synthesis in cocultures with autologous B cells; therefore, the T lymphocyte responsible for this effect is radiosensitive and is not identified by OKT8. OKT8+ lymphocytes from patients did not suppress Ig synthesis by autologous B plus T cell cocultures. However, OKT8+ cells from normal controls down‐regulated Ig synthesis by B plus T cells from patients. The abnormal proportion of helper and suppressor cells suggests that there is altered redistribution of regulatory subpopulations in peripheral blood from Sjögren's syndrome patients.
Products of polymorphonuclear cell injury inhibit IgG enhancement of monosodium urate‐induced superoxide production
Authors: Rosen Michael S. , Baker Daniel G. , Schumacher H. Ralph , Cherian Plammoottil V.
Published: February 2007

The generation of polymorphonuclear cell (PMN) superoxide ion (O2−) by monosodium urate (MSU) crystals may be important in the pathogenesis of acute gout. Coating MSU crystals with IgG prior to exposure to PMN markedly augmented O2− generation. This augmentation was inhibited by supernates, termed cell lysate, derived from sonicated PMN or PMN exposed to MSU crystals for 5 hours at 37°C. Lysate was effective in inhibiting O2− production when incubated with MSU crystals prior to, during, or after MSU crystals were exposed to IgG. No IgG could be eluted from crystals exposed to both lysate and IgG. Immunoelectron microscopy showed virtually no IgG on crystal surfaces after incubation of crystals with lysate and IgG. These data suggest that products of PMN injury can modulate further PMN responses to MSU crystals. This phenomenon provides a negative feedback loop and is one possible mechanism for the self‐limitation of acute gouty attacks.
Alterations in a cartilage matrix glycoprotein in canine osteoarthritis
Authors: Fife Rose S.
Published: February 2007

A number of biochemical abnormalities have been described in osteoarthritic (OA) cartilage, but little study has been devoted to changes in the noncollagenous, nonproteoglycan proteins of cartilage in this condition. Using a canine model of OA produced by transection of the anterior cruciate ligament of the knee, we have demonstrated that distinct alterations occur in a 550,000‐dalton cartilage matrix glycoprotein in OA canine cartilage. This protein is a major protein constituent of normal articular cartilage. Fragments which are immunologically cross‐reactive with the 550,000‐dalton protein were more abundant in OA cartilage than in normal articular cartilage. Immunofluorescence studies revealed that staining with specific antiserum to the protein was absent in OA cartilage. This was the only noncollagenous, nonproteoglycan protein noted to undergo significant changes in this model of OA.
Cyclosporin a in rheumatoid arthritis: preliminary clinical results of an open trial
Authors: Dougados Maxime , Amor Bernard
Published: February 2007

Twelve patients with refractory rheumatoid arthritis were included in a 1–year open trial of cyclosporin A (CsA), 5 mg/kg/day. Clinical efficacy was observed 1 month after beginning treatment, was well established after 4 months of therapy, and remained stable for the remainder of the 1‐year treatment period. Among the numerous side effects observed, renal toxicity and hypertension occurred suddenly during the trial and required constant monitoring, adequate therapy, and modulation of CsA dosage. Cyclosporin A seems to be an effective treatment for active rheumatoid arthritis, but it requires close monitoring for toxicity.
Modulation of cartilage destruction by select nonsteroidal antiinflammatory drugs
Authors: Herman Jerome H. , Appel Alan M. , Hess Evelyn V.
Published: February 2007

Non‐enzymatic factors produced by synovial tissue can potentially mediate cartilage destruction by inducing the synthesis and release of matrix‐degrading proteinases from chondrocytes. Pharmacologic control of this process is of potential clinical relevance. The in vitro effect of therapeutic concentrations of select nonsteroidal antiinflammatory drugs on the synthesis and activity of catabolism‐inducing cytokines produced by 6‐day explant cultures of osteoarthritic and rheumatoid synovial tissue was studied. Piroxicam regularly suppressed such factor synthesis by both types of tissue without significantly affecting total protein synthesis. This did not occur using sodium salicylate or indomethacin in osteoarthritis tissue cultures and was observed only occasionally in rheumatoid arthritis cultures. None of the nonsteroidal antiinflammatory drugs studied consistently blocked catabolism‐inducing activity in osteoarthritis tissue, whereas piroxicam more consistently inhibited activity produced by rheumatoid arthritis tissue. Results suggest that the catabolism‐inducing factors produced by the 2 tissue sources may differ.