bluuebunny/crossref_metadata_2025 huggingface dataset:
Methylprednisolone infusion therapy in rheumatoid arthritis patients. The effect on synovial fluid lymphocyte subsets and inflammatory indices
Authors: Bertouch James V. , Roberts‐Thomson Peter J. , Smith Malcolm D. , Woodruff Timothy G. , Brooks Peter M. , Bradley John
Published: February 2007

Paired samples of synovial fluid (SF) and blood were obtained prior to and at 4 and 24 hours following high‐dose methylprednisolone infusion therapy in a group of patients with refractory rheumatoid arthritis. After therapy there was a significant decrease in numbers of polymorphonuclear leukocytes, lymphocytes, immune complexes, and C‐reactive protein in the SF. Measurement of lymphocyte subsets, using monoclonal antibodies, revealed that at 4 hours postinfusion, there was a disproportionate decrease in the percentage of SF lymphocytes expressing class II antigens (HLA‐DR or Ia‐like). These data suggest that glucocorticoids induce rapid changes in SF indices of disease activity and may directly influence T cell activation within the rheumatoid joint.
IgM anti‐histone H‐3 antibody associated with undifferentiated rheumatic disease syndromes
Authors: Molden Daniel P. , Klipple Gary L. , Peebles Carol L. , Rubin Robert L. , Nakamura Robert M. , Tan Eng M.
Published: February 2007

A distinctive type of speckled antinuclear antibody staining pattern was identified by indirect immunofluorescence on mouse kidney substrate in 4.8% of 5,976 specimens analyzed for antinuclear antibodies. This pattern, termed variable large speckles (VLS), consisted of 3–10 nuclear speckles ranging in size from approximately 0.2–2.0μ. The pattern could be differentiated from other indirect immunofluorescence patterns related to specific antibodies. The predominant immunoglobulin isotype demonstrating the VLS pattern was IgM in 27 of 28 sera examined and IgG in 1 serum. VLS sera had substantial IgM antibodies to histone demonstrated by enzyme immunoassay, and further analysis of representative sera showed predominant antibody activity to histone class 3 (H‐3). Adsorption with histone H‐3 resulted in decrease or removal of antibody producing the VLS pattern. Available information showed that most patients with IgM antibodies of the VLS pattern had undifferentiated connective tissue disease symptoms. They were characterized by a heterogeneity of chronic symptoms including arthralgias, myalgias, inflammatory polyarthritis, myositis, sicca symptoms, and pleurisy associated with elevation of the erythrocyte sedimentation rate. It remains to be determined whether the IgM anti‐histone H‐3 profile of these patients is a transient or long‐standing serologic characteristic.
Composition and glycosaminoglycan metabolism of articular cartilage from habitually loaded and habitually unloaded sites
Authors: Slowman Sally D. , Brandt Kenneth D.
Published: February 2007

The uronic acid (proteoglycan, PG) content of cartilage from habitually unloaded sites of normal canine femoral condyles has been shown to be lower than that from habitually loaded regions, even though the glycosaminoglycan (GAG) synthesis is similar. We investigated whether the GAG degradation in unloaded cartilage would be greater than that in loaded cartilage, and we obtained comparative biochemical data concerning the PGs and organization of the extracellular matrix of normal loaded and unloaded cartilage. PG extractability (determined by sequential guanidinium chloride extracts of cartilage), percentage of PGs forming large aggregates, and hydrodynamic size of the PG monomers (determined by Sepharose 2B chromatography) were essentially the same in loaded and unloaded cartilage. As expected, the uronic acid content of unloaded cartilage was 20% lower than that of loaded cartilage (P < 0.02), while the water and DNA contents of the 2 tissues were not statistically different. There was no difference in the rate of net 35SO4‐GAG synthesis in organ cultures of loaded and unloaded cartilage. Moreover, there was no appreciable difference in the rates of 35SO4‐GAG degradation of loaded and unloaded cartilage, as determined by 35SO4 pulse‐chase studies. We have previously shown that selective cyclic compressive stresses applied in vitro to cartilage from loaded areas of canine femoral condyles may increase 35SO4‐GAG synthesis. The present results suggest that the rates of GAG metabolism in loaded and unloaded cartilage under atmospheric pressure in vitro may not reflect the rates which exist in articular joints under compressive loads in vivo.
Homologous type II collagen induces chronic and progressive arthritis in mice
Authors: Holmdahl Rikard , Jansson Liselott , Larsson Erik , Rubin Kristofer , Klareskog Lars
Published: February 2007

Native mouse type II collagen was used for immunization of DBA/1 mice. Arthritis developed exclusively in male animals and was characterized by a variable and delayed onset, a slow and progressive development, and frequent exacerbations of disease in several joints including those that were previously affected. Titers of anti‐type II collagen autoantibodies were found not to correlate well with arthritis development. It appears that experimental arthritis induced with homologous type II collagen resembles rheumatoid arthritis in humans, both in certain clinical features and in the lack of correspondence between anti‐type II collagen autoantibody titers and disease symptoms.
Anti‐Ro (SS‐A) and Anti‐La (SS‐B) in patients with Sjögren's syndrome
Authors: Harley John B. , Alexander Elaine L. , Bias Wilma B. , Fox Owen F. , Provost Thomas T. , Reichlin Morris , Yamagata Hajime , Arnett Frank C.
Published: February 2007

Clinical, serologic, and genetic findings in Sjögren's syndrome patients were correlated with quantitative determinations for antibody against Ro (SS‐A), La (SS‐B), and nRNP (Sm) using newly developed, sensitive solid‐phase assays. In 86 Sjögren's syndrome patient sera, more than 96% had anti‐Ro (SS‐A), and 87% had anti‐La (SS‐B), spanning a 4.8 log10 range of autoantibody concentration, whereas only 95% of the patients had anti‐nRNP (Sm). Low levels of anti‐Ro (SS‐A) and anti‐La (SS‐B) were found in 10% and 12.5%, respectively, of the 40 normal control sera. In Sjögren's syndrome patients, the level of anti‐Ro (SS‐A) correlated strongly with that of anti‐La (SS‐B) (r = 0.80; P 0.0001) but not with the level of anti‐nRNP (Sm). We found much higher levels of anti‐Ro (SS‐A) and anti‐La (SS‐B) in patients with purpura, leukopenia, lymphopenia, and increased polyclonal gamma globulins than in those without these conditions (between 4.3‐fold and 17‐fold higher; P < 0.001 to P < 0.05). Anti‐Ro (SS‐A) and anti‐La (SS‐B) levels correlated with the rheumatoid factor titer and with the concentrations of total globulin, IgG, and IgA, but not with the IgM concentration. The association of rheumatoid factor titer with levels of anti‐Ro (SS‐A) and anti‐La (SS‐B) occurred only in patients with primary Sjögren's syndrome. Antinuclear antibody titers correlated with levels of anti‐Ro (SS‐A) and anti‐nRNP (Sm). HLA‐DR3‐positive patients had higher levels of anti‐Ro (SS‐A) and anti‐La (SS‐B).
Food‐induced (allergic) arthritis. Inflammatory arthritis exacerbated by milk
Authors: Panush Richard S. , Stroud Robert M. , Webster Ella M.
Published: February 2007

Suggestive, but largely unproven, observations have associated arthritis with environmental antigens, including foods. We studied a patient with inflammatory arthritis in a prospective, “blinded,” controlled fashion to determine whether her symptoms were associated with food sensitivities. This 52‐year‐old white woman with 11 years of class I, stage I, active disease, had symptomatic exacerbations allegedly associated with meat, milk, and beans. We observed an increase in symptoms following an unblinded food challenge and then studied her in our clinical research unit. On her normal diet for 6 days, she averaged 30 minutes of morning stiffness, 9 tender joints, 3 swollen joints, 87% subjective assessment (100% = best possible), and 89% examiner assessment. While she was fasting (3 days) or taking Vivonex (2 days), we noted no morning stiffness, tender joint score of 1, swollen joint score of 0, and assessments of 100% (P < 0.05 versus normal diet). She was then nourished with Vivonex for 33 days without difficulty and challenged in a blinded fashion at mealtimes with lyophilized foods placed into opaque capsules. Four milk challenges (equivalent to ≧8 ounces per meal) produced up to 30 minutes of morning stiffness, 14 tender joints, 4 swollen joints, subjective assessment of 85%, and objective assessment of 80% (P < 0.05 versus fasting‐Vivonex), peaking 24–48 hours postchallenge. Placebo and other foods (lettuce and carrots) were without effect. Immunologic studies suggested both delayed and immediate cutaneous reactivity to milk, no elevation in IgE anti‐milk, marked increases of IgG and IgG4 anti‐milk levels, marginally increased IgG‐milk circulating immune complexes, and in vitro cellular sensitivity to milk. These data relate symptomatic exacerbation of inflammatory arthritis with immunologic hypersensitivity to milk in this patient. This observation suggests new insights in the pathogenesis of inflammatory joint disease and its therapeutic control.
Poems syndrome. Study of a patient with proteinuria, microangiopathic glomerulopathy, and renal enlargement
Authors: Fam Adel G. , Rubenstein Joel D. , Cowan Donald H.
Published: February 2007

We studied a patient with POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal [M]‐protein, skin changes) who was also found to have renal enlargement and microangiopathic glomerulopathy. The latter finding is unusual in POEMS syndrome patients, and the associated symptoms can lead to confusion in diagnosis. We emphasize the importance of considering POEMS syndrome in the differential diagnosis of patients who have unexplained neuropathy, scleroderma‐like skin changes, and/or monoclonal gammopathy.
Normal anti‐Klebsiella lymphocytotoxicity in ankylosing spondylitis
Authors: Kinsella T. Douglas , Fritzler Marvin J. , Lewkonia Raymond M.
Published: February 2007

We compared in vitro lymphocytotoxicity (LCT) of peripheral blood lymphocytes (PBL), obtained from patients with ankylosing spondylitis (AS) and normal controls (NC). Assays were performed with antibacterial antisera prepared from AS‐ and NC‐derived Klebsiella and coliforms Escherichia coli. LCT assessed by eosin staining was not significantly different in PBL of 12 AS patients and 28 controls when reacted with 3 Klebsiella and 1 E coli antisera. LCT assessed by 51Cr release was not significantly different for PBL of 20 age‐and sex‐matched pairs of AS patients and NC when reacted with 3 Klebsiella and 1 E coli antisera. Similarly, LCT‐51Cr of PBL of 15 matched AS and NC pairs was not significantly different for anti‐K21, a serotype putatively implicated in Klebsiella‐HLA‐B27 antigenic cross‐reactivity. Our results do not support the notion of molecular mimicry between Klebsiella and B27 in the pathogenesis of primary AS.
Oxygen radicals as effectors of cartilage destruction. Direct degradative effect on matrix components and indirect action via activation of latent collagenase from polymorphonuclear leukocytes
Authors: Burkhardt H. , Schwingel M. , Menninger H. , Macartney H. W. , Tschesche H.
Published: February 2007

Degradation of intact cartilaginous tissue (bovine nasal cartilage) by oxygen‐derived free radicals (ODFR) generated enzymatically by xanthine oxidase and hypoxanthine was studied. The degree of tissue destruction was determined by measuring the indentation under a defined compression force as well as by the loss of uronic acid‐ and hydroxyproline‐containing matrix components. Cartilage slices altered by prior elastase treatment were more susceptible to oxygen radical attack than were intact tissue specimens. Degradation of cartilage matrix by ODFR was strongly inhibited by superoxide dismutase or catalase. Coincubation of latent collagenase from polymorphonuclear leukocytes with the ODFR‐generating system led to activation of collagenolytic activity, resulting in marked degradation of the bovine cartilage slices. In further studies, activated polymorphonuclear leukocyte‐collagenase was shown to degrade intact human articular cartilage to a degree of mechanical insufficiency. Thus, our assay system serves as an in vitro model of tissue damage, which may be relevant to pathophysiologic states such as rheumatoid arthritis.
Characterization of the antibody response in mice with type II collagen–induced arthritis, using monoclonal anti–type II collagen antibodies
Authors: Holmdahl Rikard , Rubin Kristofer , Klareskog Lars , Larsson Erik , Wigzell Hans
Published: February 2007

Twenty monoclonal antibodies reactive with type II collagen were characterized as to their determinant specificity and their reactivity with cartilage‐derived components. The monoclonal antibodies reacted with 7 different epitopes on the native type II collagen triple helical structure. Antibodies defining 3 of these epitopes occurred more frequently in sera from arthritic mice than in sera from nonarthritic mice. In vivo injection of some selected autoreactive antibodies caused synovitis, but in no case did it give rise to full‐blown arthritis.
Progesterone secretion in the rat in response to an adjuvant arthritis challenge
Authors: Latman Neal S. , Kishore Vimal , Bruot Brent
Published: February 2007

This study was undertaken to determine if progesterone is secreted in response to an adjuvant‐induced arthritis challenge in the rat. While the arthritic rat paw volume increased 33%, the plasma progesterone concentration increased from 502 pg/ml in the control rats to 1,202 pg/ml in the arthritic animals. A strong positive correlation was found between the degree of edema and the plasma progesterone concentrations. We suggest that progesterone may play an antiinflammatory role in adjuvant arthritis in the rat.
Interleukin‐1 lymphocyte chemotactic activity in rheumatoid arthritis synovial fluid
Authors: Miossec Pierre , Dinarello Charles A. , Ziff Morris
Published: February 2007

We examined the role of interleukin‐1 (IL‐1) in the chemotactic activity of rheumatoid arthritis (RA) synovial fluid (SF). Crude RA SF was found to be chemotactic for B cells and T cells. After AcA 54 gel filtration, the principal peaks of chemotactic activity were found in the 5‐kd, 16‐kd, and 60‐kd fractions. The majority of the chemotactic activity for both the B cells (74‐85%) and the T cells (69‐78%) was removed from these fractions by treatment with anti‐IL‐1 antibody. However, in crude SF, approximately 60% of the chemotactic activity for B cells and 40% of that for T cells was removed, indicating the presence of additional chemotactic factors in RA SF. IL‐1 activity, measured by the thymocyte proliferation assay, was demonstrated in RA SF AcA 54 Ultrogel fractions after separation from inhibitors of thymocyte proliferation that are present in crude SF. On chromatofocusing of the 16‐kd fraction, the principal peaks of both thymocyte proliferation activity and chemotactic activity were present in the same fractions with pl values of 6.8, 5.7, and 5.2, which are characteristic of IL‐1. The demonstration of IL‐1‐associated chemotactic activity in RA SF may reflect the presence in the RA synovial membrane (including both the lining layer and the subsynovial layer) of activated macrophages, interstitial histiocytic cells, and other IL‐1‐producing cells, such as endothelial cells. These findings suggest that such cells may attract lymphocytes to their environment by secretion of IL‐1.
Effects of gold therapy on the synthesis and quantity of serum and synovial fluid IgM, IgG, and IgA rheumatoid factors in rheumatoid arthritis patients
Authors: Hanly John G. , Hassan Jaythoon , Whelan Alex , Feighery Conleth , Bresnihan Barry
Published: February 2007

Eleven patients with active rheumatoid arthritis were monitored prospectively while receiving up to 1 gm of gold sodium thiomalate. There was a significant decrease in serum and synovial fluid IgG, IgA, and IgM rheumatoid factor (RF) levels over the period of study. Comparison of changes in serum RF and total immunoglobulin levels indicated a selective effect on RF production. These observations were supported by changes in the spontaneous in vitro production of IgM‐RF and total IgM by peripheral blood mononuclear cells. Studies of synovial membrane synthesis showed a downward trend in immunoglobulin and RF production, but this did not reach statistical significance. A differential effect on the various RF classes was also noted. The most profound effect was on IgM‐RF production; whereas, changes in IgG‐RF production were least affected. These results suggest a selective and differential effect of gold salts on RF production.
An experimental model for hydrogen peroxide–induced tissue damage. Effects of a single inflammatory mediator on (peri)articular tissues
Authors: Schalkwijk Joost , van den Berg Wim B. , van de Putte Levinus B. A. , Joosten Leo A. B.
Published: February 2007

Hydrogen peroxide is receiving increasing attention as a mediator of tissue damage during inflammation. To evaluate its destructive potential in vivo, we devised a model in which hydrogen peroxide is, initially, the sole mediator of tissue damage. Glucose oxidase, which was made cationic to obtain good retention in tissue, was injected intraarticularly in mouse knee joints. This enzyme produces hydrogen peroxide, using endogenous glucose as a substrate. The local production of hydrogen peroxide induced drastic vascular damage, as measured by 99mTc uptake and leakage of 125I‐albumin. The chondrocyte proteoglycan synthesis was severely inhibited, as measured by 35SO4 incorporation. Histologic examination showed impressive inflammatory and degenerative changes, including periarticular infiltration, chondrocyte death, subchondral erosions, and muscle necrosis. Intraarticular administration of catalase could inhibit these vascular effects and cartilage damage. Systemic administration of ebselen, a synthetic glutathione peroxidase‐like compound, provided partial protection. Indomethacin and piroxicam were not effective in the acute phase. We think this model is useful both for testing drugs that are purported to act as scavengers of hydrogen peroxide and for studying chronic destructive processes.
Evaluation of amitriptyline in primary fibrositis. A double‐blind, placebo‐controlled study
Authors: Carette Simon , McCain Glenn A. , Bell David A. , Fam Adel G.
Published: February 2007

Seventy patients with primary fibrositis satisfying Smythe's criteria were studied in a 9‐week double‐blind trial comparing 50 mg amitriptyline with placebo. Fifty‐nine patients completed the trial: 27 were treated with amitriptyline, and 32 took a placebo. The patients who received amitriptyline improved significantly in their morning stiffness and pain analog scores at 5 and 9 weeks, compared with baseline scores, whereas no changes were noted in these parameters in the placebo group. Fibrositic point tenderness did not improve significantly in either of the treatment groups. When compared with the placebo group, the amitriptyline group improved significantly with respect to sleep pattern and patient and physician global assessments. Our data indicate that amitriptyline has some therapeutic benefit in patients with primary fibrositis.
The effect of sodium selenite on chondrocytes in monolayer culture
Authors: Wei Xiqin , Wright George C. , Sokoloff Leon
Published: February 2007

The effect of sodium selenite on DNA and sulfated proteoglycan synthesis by cultured rabbit articular and growth plate chondrocytes was studied as an in vitro model for Kashin‐Beck disease. The selenium content of a defined medium (DMEM, fibroblast growth factor, insulin, and dexamethasone) was below the limit of detection by isotope dilution mass spectrometry. The chondrocytes were viable in the Se‐free basal medium. Selenite over a range of 5 × 10−9M to 5 × 10−7M had no stimulatory effect on DNA or sulfated proteoglycan synthesis by either type of chondrocyte or skin fibro‐blasts. Proliferation of bovine endothelial cells was enhanced by 5 × 10−7M Se. At Se concentrations of ≧ 10−6M, there was progressive inhibition of cell growth and radiosulfate incorporation of the connective tissue cells; bovine endothelial cells were more resistant. Twice equimolar concentrations of vitamins C and E exerted no protective effect against the cytotoxicity of higher concentrations of Se. Se supplementation also failed to stimulate growth of human infant chondrocytes. The model enabled simulation of conditions of hyposelenosis below those encountered in nature. The data provide no evidence that chondrocytes have idiosyncratic requirements for Se, and do not support the hypothesis that Se deficiency is a major etiologic factor in Kashin‐Beck disease.
Complement‐activating abilities of defined antinuclear antibodies
Authors: Kanayama Yoshiharu , Peebles Carol , Tan Eng M. , Curd John G.
Published: February 2007

A complement‐fixing immunofluorescence assay on HEp‐2 cells was used to assess the ability of various antinuclear antibodies (ANA) to activate complement. Sera which contained only specific antibodies to nuclear RNP, SS‐B/La, centromere, Sm antigen, double‐stranded DNA, and/or nuclear histone were selected. Relative abilities of various ANA to activate complement were determined from the ratio of titers of C3, C4, or properdin‐fixing ANA to the IgG ANA titers. Nuclear RNP‐anti‐RNP complexes activated and deposited significantly more complement C3 than other ANA (P < 0.02). Antibodies to SS‐B/La, centromere, and Sm activated more complement than anti‐DNA or antihistone (P < 0.02). Antihistone antibodies activated the least complement. These studies demonstrate that different ANA have significantly different orders of complement‐activating capabilities when bound to their respective nuclear antigens.
Increased proto‐oncogene expression in peripheral blood lymphocytes from patients with systemic lupus erythematosus and other autoimmune diseases
Authors: Boumpas D. T. , Tsokos G. C. , Mann D. L. , Eleftheriades E. G. , Harris C. C. , Mark G. E.
Published: February 2007

Using RNA hybridization techniques, we examined the expression of proto‐oncogenes associated with lymphocyte activation in vitro in patients with systemic lupus erythematosus and other autoimmune diseases. T and B lymphocytes from these patients were found to have significantly increased expression of c‐myc, c‐myb, and c‐raf RNA when compared with those of normal individuals. Among the mononuclear cell subpopulations, B lymphocytes expressed higher levels of RNA for these proto‐oncogenes compared with the T lymphocytes. Since prompt expression of these and other proto‐oncogenes occurs in fibroblasts and lymphocytes following mitogenic stimulation, we propose that the present findings reflect the pathologically activated state of various lymphocytic subpopulations which is observed in systemic lupus erythematosus and in other autoimmune diseases. Endogenous and exogenous factors which lead to the expression of autoimmunity might share the induction of proto‐oncogene expression as a common pathogenetic step.
Reproducibility of synovial fluid analyses. A study among four laboratories
Authors: Schumacher H. Ralph , Sieck Marie S. , Rothfuss Susan , Clayburne Gilda M. , Baumgarten Dorothy F. , Mochan Bonnie S. , Kant Jeffrey A.
Published: February 2007

Aliquots from 30 synovial fluids were submitted to 4 laboratories for comparison of leukocyte counts and differential cell counts, and to 3 laboratories for a search for and identification of crystals. Leukocyte counts showed only fair correlation (coefficients of 0.76–0.80) with the reference laboratory. In synovial fluid from 4 patients, there was sufficient difference in leukocyte counts to cause the fluids to be erroneously classified as either “inflammatory” or “noninflammatory.” In 12 of 24 fluid specimens examined, percentages of neutrophils fell outside the 95% confidence limits of the value determined by the reference laboratory. In 7 of the 11 patients with crystals reported, discrepancies were found between the reports from 1 or more laboratories. More attention to quality control of synovial fluid analyses is important.
Comparison of pain properties in fibromyalgia patients and rheumatoid arthritis patients
Authors: Leavitt Frank , Katz Robert S. , Golden Harvey E. , Glickman Paul B. , Layfer Lawrence F.
Published: February 2007

Pain properties of 50 fibromyalgia patients were examined and compared with pain properties of 50 rheumatoid arthritis patients. In both fibromyalgia and rheumatoid arthritis, pain was bilateral, involved multiple sites, and was of equal intensity (60.8 versus 58.7, respectively, on a scale of 100). Fibromyalgia pain, however, was less localized to the joints and suggested greater spatial diffusion. It involved more kinds of pain experiences (radiating, steady, spreading, spasms, gnawing, unlocalized, pricking, crushing, shooting, pressing, splitting, cramping, nagging, and pins and needles), and was dispersed over larger areas of the body. The anatomic sites best for discrimination between patients with fibromyalgia and patients with rheumatoid arthritis were the lower back, thigh, abdomen, head, and hips for fibromyalgia, and wrist, foot, and fingers for rheumatoid arthritis. The traditional clinical description of aching and stiffness does not appear to accurately describe the complexity of the fibromyalgia pain syndrome.
Arthropathy associated with factor XIII deficiency
Authors: Thakker Suman , McGehee William , Quismorio Francisco P.
Published: February 2007

A 47‐year‐old man with congenital factor XIII deficiency developed recurrent hemarthrosis of the right ankle. He had radiologic evidence of permanent joint damage. A review of the literature revealed that hemarthrosis is not a rare manifestation of factor XIII deficiency; however, destructive changes in the joints are relatively uncommon in this disorder, in contrast with those changes seen in patients with classic hemophilia and arthropathy. The bleeding manifestations of factor XIII deficiency are readily correctable by plasma or cryoprecipitate infusions; this may account for the preservation of joint function and structure.
The safety and efficacy of the use of methotrexate in long‐term therapy for rheumatoid arthritis
Authors: Kremer Joel M. , Lee Joong Kil
Published: February 2007

Twenty‐nine patients participated in a prospective study of the safety and efficacy of oral methotrexate in the treatment of refractory rheumatoid arthritis. Patients received a mean dosage of 12.4 mg weekly over a mean duration of 29.1 months. All patients had liver biopsies at baseline, 2 years, and annually thereafter. Patients improved significantly by all clinical measures of efficacy after 1 month; maximum improvement tended to occur after approximately 6 months of therapy. Radiographs showed improvement of erosive disease in 7 of 11 patients measured. There was a significant reduction in mean prednisone dosage. Four patients required an increase in the dosage of methotrexate after prolonged therapy, because of declining clinical response. Toxicity was noted at some time in 26 of 29 patients (90%), but reactions universally became mild and tolerable after adjustment of the dosage. No significant hepatotoxicity was found in 60 sequential liver biopsies, although elevated transaminase levels were noted at some time in 20 of 29 patients (70%).
Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients: Association with hepatic folate deficiency and formation of polyglutamates
Authors: Kremer Joel M. , Galivan John , Streckfuss Anita , Kamen Barton
Published: February 2007

Serum and red blood cell methotrexate (MTX) levels, as well as hepatic levels of MTX and folate, were analyzed in 24 patients who had received long‐term oral MTX weekly for the treatment of rheumatoid arthritis. The serum MTX level peaked rapidly and was insignificant after 24 hours. The red blood cell MTX level was not related to the interval from the last MTX dose. In hepatic tissue obtained by liver biopsy, MTX was found in a predominantly polyglutamated form with depleted hepatic folate stores when compared with baseline specimens. A brief period of therapy with oral folinic acid repleted hepatic folate. It is possible that MTX hepatotoxicity is related to reduced hepatic folate levels and formation of MTX polyglutamates.
Altered distribution of debrisoquine oxidation phenotypes in patients with systemic lupus erythematosus
Authors: Baer Alan N. , McAllister C. B. , Wilkinson Grant R. , Woosley Raymond L. , Pincus Theodore
Published: February 2007

Oxidative metabolism in patients with systemic lupus erythematosus (SLE) was studied using the antihypertensive drug, debrisoquine. The metabolism of this drug to its principal metabolite, 4‐hydroxy‐debrisoquine, is catalyzed by a discrete isozyme of cytochrome P‐450. The extent of this reaction exhibits genetic polymorphism, with 2 phenotypes, “poor metabolizers” and “extensive metabolizers,” discernible in the normal population. We observed the poor metabolizer debrisoquine phenotype in 9 of 42 patients with idiopathic SLE (21%), in contrast with 12 of 147 healthy volunteers (8%), which is a significant difference in frequency (P < 0.04). These data provide further evidence for altered oxidative metabolism in SLE and support the concept that genetic differences in oxidative metabolism of endogenous compounds, such as sex steroid hormones, or of xenobiotics might influence susceptibility to SLE.
The impact of childhood rheumatic diseases on the family
Authors: McCormick Marie C. , Stemmler Margaret M. , Athreya Balu H.
Published: February 2007

Much of the burden of providing health care and other services for children with rheumatic diseases falls on the parents, but little is known about the impact of these conditions on the family. A survey of the parents of 138 children revealed that the most important predictors of high family impact were the number of the child's activities of daily living that were limited by illness, the educational attainment of the mother, the child's sex, the mother's perception of the child's health, and the volume of medical care use. Our results provide guidelines for identifying families who are most vulnerable to the stress of having a child with a rheumatic disease.
The face scale: A brief, nonverbal method for assessing patient mood
Authors: Lorish Christopher D. , Maisiak Richard
Published: February 2007

Validity and reliability studies were conducted on the Face Scale, a very brief, pictorial scale of mood which uses a sequence of 20 faces and does not require reading literacy. Correlational and experimental evidence of the Face Scale's construct validity is presented, as well as its test‐retest reliability. Recommendations are made for its use as a screening tool and for additional validity studies.
Aseptic arthritis in a man with toxic shock syndrome
Authors: Gertner Elie , Inman Robert D.
Published: February 2007

Synovitis in toxic shock syndrome (TSS) is an unusual finding. A 31‐year‐old man presented with pain and swelling in both knees and was found to have TSS, secondary to a septic bursitis caused by Staphylococcus aureus. Immune complexes were not detected in serum or synovial fluid, and the S aureus was not recovered from the inflamed joints. Antibodies against the TSS toxin‐1 were detected in serum and synovial fluid, but in lower levels than would be seen in a normal control serum. Complement studies implicated alternative pathway activation by a marked diminution in C3 levels compared with C4 levels, and by lower levels of factor B than would be found in other inflammatory joint diseases. The diagnostic dilemma posed by TSS in a man is discussed.
Clinical and serologic associations of the antiribosomal P protein antibody
Authors: Bonfa Eloisa , Elkon Keith B.
Published: February 2007

Antibodies to the ribosomal P proteins (anti‐P) were detected, by Western blot analysis, in the sera of 20 of 114 patients with various autoimmune disorders. Eighty‐five percent of the patients with anti‐P had systemic lupus erythematosus (SLE). Of 93 randomly selected patients, the frequency of anti‐P was 7 of 59 SLE patients (12%) and 0 of 34 non‐SLE patients. Approximately one‐third of the patients with anti‐P antibodies were male; approximately half were black. In contrast to the findings of some previous studies which used isolated ribosomes as antigen, an increased frequency of renal disease was not observed. Although the overall frequency of central nervous system lupus was similar in SLE patients with and those without anti‐P, 6 of 6 patients with psychosis had anti‐P antibodies. Western blotting was the most sensitive and specific method for the detection of anti‐P antibodies; counter‐immunoelectrophoresis and cytoplasmic indirect immu‐nofluorescence were positive in only 47% and 65% of the anti‐P‐positive patients, respectively. Although 53% of the SLE patients with anti‐P had concomitant anti‐Ro antibodies, none had anti‐La (as detected by counterim‐munoelectrophoresis). Anti‐P antibodies, therefore, appear to be relatively specific serologic markers for SLE and may be detected in the serum even when antibodies to double‐stranded DNA are not found.
The use of immunoblotting and immunoprecipitation of (U) small nuclear ribonucleoproteins in the analysis of sera of patients with mixed connective tissue disease and systemic lupus erythematosus: A cross‐sectional, longitudinal study
Authors: Pettersson Ingvar , Wang Grace , Smith Elaine I. , Wigzell Hans , Hedfors Eva , Horn John , Sharp Gordon C.
Published: February 2007

Antibodies to ribonucleoproteins (RNP) and to the Sm antigen in sera from patients with mixed connective tissue disease (MCTD) and systemic lupus erythematosus were studied using the techniques of immunoblotting and immunoprecipitation of U small nuclear RNPs. A cross‐sectional study indicated that antibodies reacting with a 68K protein were associated with anti‐RNP specificity in MCTD, but rarely occurred in systemic lupus erythematosus patients' sera. A longitudinal study demonstrated the persistence of MCTD blotting patterns over many years, and the subsequent disappearance of those specificities in sera from patients who were in prolonged remission.
Intraarticular triamcinolone hexacetonide in the management of chronic arthritis in children
Authors: Allen R. C. , Gross K. R. , Laxer R. M. , Malleson P. N. , Beauchamp R. D. , Petty R. E.
Published: February 2007

The use of intraarticular triamcinolone hexacetonide in the management of persistent arthritis of the knee joint that is unresponsive to nonsteroidal anti‐inflammatory drugs was prospectively evaluated in 40 children with chronic arthritis. Of 49 knees that were injected, 63.3% maintained complete resolution of effusion and other signs of inflammation at the 6‐month followup. This favorable outcome correlated with a young age, a short disease duration, and a higher dose of triamcinolone hexacetonide. At the 12‐month followup, 45% of the injected knees remained in remission.
Increased calcification of growth plate cartilage as a result of compressive force in vitro
Authors: Klein‐Nulend J. , Veldhuijzen J. P. , Burger E. H.
Published: February 2007

The influence of intermittent compressive force (ICF) and of continuous compressive force (CCF) on calcification of growth plate cartilage was investigated, using organ cultures of fetal mouse cartilaginous long bone rudiments. Sixteen‐day‐old metatarsal rudiments, still consisting of uncalcified cartilage, were isolated and cultured for 5 days. Initial calcification of hypertrophic cartilage occurred under control conditions (atmospheric pressure), and under the influence of ICF or CCF by intermittently or continuously compressing the gas phase above the culture medium. Calcification was monitored by means of 45Ca and 32P incorporation into calcium‐phosphate mineral and by morphometric methods. Both ICF and CCF increased cartilage calcification, but ICF was about twice as effective as CCF. Killed rudiments did not calcify during the culture period, nor did ICF or CCF increase the incorporation of label. The effects of ICF and CCF on calcification could not be mimicked by increasing the Po2 and Pco2 levels in the gas phase. The length of the central zone of calcified cartilage was significantly increased by ICF and CCF. We conclude that hypertrophic chondrocytes respond directly to ICF and CCF by an increased deposition of calcium‐phosphate mineral in the matrix. Discontinuous mechanical stimulation evokes a higher cellular response than does continuous stimulation.
In vitro cell proliferation and proteoglycan synthesis of rabbit meniscal fibrochondrocytes as a function of age and sex
Authors: Webber Richard J. , Zitaglio Teresa , Hough Aubrey J.
Published: February 2007

Meniscal fibrochondrocytes from male and female New Zealand white rabbits, ages 6, 12, and 24 months, were grown in primary and secondary monolayer cell culture. Neither age nor sex affected the majority of their cell culture characteristics. Cells from young males (6 months old) synthesized greater amounts of sulfated proteoglycans than did those from young females, but by 2 years of age, this result was reversed. All age groups synthesized 2 classes of proteoglycans, based on hydrodynamic size, but the ratio of the 2 classes changed as a function of age. Overall, the meniscal fibrochondrocytes from both skeletally immature and skeletally mature rabbits of both sexes were capable of proliferation and matrix synthesis in vitro.
Systemic lupus erythematosus is not genetically linked to the beta chain of the T cell receptor
Authors: Fronek Zdenka , Lentz Daniel , Berliner Nancy , Duby Allan D. , Klein Karen A. , Seidman J. G. , Schur Peter H.
Published: February 2007

The genomic DNA polymorphism of the beta chain of the T cell receptor was examined. The restriction fragment length polymorphism distribution was similar in systemic lupus erythematosus patients, their relatives, and normal controls. Our observations suggest that these genes are not coinherited with genes responsible for systemic lupus erythematosus.
Cryoglobulinemia and hepatitis B markers in north African Jews with Raynaud's disease
Authors: Horowitz Jacob , Klein Mordechai , Sukenik Shaul
Published: February 2007

Mixed cryoglobulinemia was discovered in 11 of 20 patients with Raynaud's disease. Hepatitis B surface markers were found in 10 of these patients with cryoglobulinemia. All patients with cryoglobulinemia were female, and 10 were of northern African origin. This study indicates that, in a population with a high prevalence of hepatitis B infection, mixed cryoglobulinemia is an important etiologic factor in Raynaud's disease.
Complement activation during systemic lupus erythematosus: C3A and C5a anaphylatoxins circulate during exacerbations of disease
Authors: Belmont H. Michael , Hopkins Patricia , Edelson Henry S. , Kaplan Howard B. , Ludewig Rocio , Weissmann Gerald , Abramson Steven
Published: February 2007

To determine whether activated complement components appear in the circulation of patients with systemic lupus erythematosus (SLE), we measured C5a and C3a by radioimmunoassay. Mean C5a concentration in the plasma of acutely ill SLE patients was 46.0 ng/ml, compared with 17.1 ng/ml in normal controls (P < 0.01). Mean C3a concentration in patients with severe disease was 526 ng/ml, compared with 134 ng/ml in controls (P < 0.01). In patients with moderately active SLE, the mean C3a concentration, but not the mean C5a concentration, was also elevated. In addition, C3a was elevated in 15 of 21 patients with active SLE, whereas low levels of C3 or C4 were noted in only 7 of these 21 patients. We conclude that the measurement of complement‐derived anaphylatoxins may be useful in the management of patients with SLE. In addition, we suggest that these circulating mediators may contribute to the pathogenesis of vascular injury in patients with the disease.
Auto antibodies in the cerebrospinal fluid of patients with systemic lupus erythematosus
Authors: Golombek Steven J. , Graus Francesc , Elkon Keith B.
Published: February 2007

Autoantibodies may play an important role in the pathogenesis of central nervous system (CNS) disease in systemic lupus erythematosus (SLE). We obtained cerebrospinal fluid (CSF) and, in some cases, sera from 19 SLE patients with CNS lupus and from 12 SLE patients without CNS lupus. Autoantibodies to saline soluble cellular antigens were detected in the CSF of lupus patients and reflected those present in the serum. These antibodies were distinct from the previously described antineuronal antibodies. Analysis of the fine specificities of the anti‐saline soluble cellular antigen antibodies revealed that the antiribosomal P protein antibody was present in 4 of 4 patients with lupus psychosis and was enriched in the CSF of 1 patient. Sera containing antiribosomal P protein showed prominent cytoplasmic staining of human cortical neurons, as well as an epithelial cell substrate. These observations, together with the increase in intrathecal IgG synthesis detected in 71% of patients tested, suggest that several populations of antibodies may contribute to the enhanced immunologic activity in the CSF of CNS lupus patients.
Cryoglobulinemia in autoimmune rheumatic diseases: Evidence of circulating monoclonal cryoglobulins in patients with primary Sjögren's syndrome
Authors: Tzioufas A. G. , Manoussakis M. N. , Costello R. , Silis M. , Papadopoulos N. M. , Moutsopoulos H. M.
Published: February 2007

The incidence and nature of cryoglobulins, as well as their correlation with the clinical and serologic picture of Sjögren's syndrome (SS), were studied in the sera of 30 consecutive primary SS patients. Sera from 29 patients with systemic lupus erythematosus, 58 patients with rheumatoid arthritis, and 125 healthy blood donors were also studied. It was shown that one‐third of the patients with SS had cryoglobulinemia. These cryoglobulins were mixed monoclonal IgM immunoglobulins, whereas those observed in systemic lupus erythematosus and rheumatoid arthritis patients were mixed polyclonal. The nature of the cryoglobulins was demonstrated using high‐resolution electrophoresis combined with immunofixation. The presence of cryoglobulins in the sera of SS patients correlated with extraglandular disease and with antibodies to Ro (SS‐A) and IgM rheumatoid factor. SS patients with cryoglobulins had lower serum C4 levels than did patients without cryoglobulins. These findings suggest that SS expresses, in addition to polyclonal B cell hyperreactivity, a monoclonal process in the absence of lymphoid neoplasia. Further, they show that the extraglandular manifestations of the syndrome may be due to an immune complex‐mediated pathology.
Expression of histocompatibility antigen HLA—DR by salivary gland epithelial cells in Sjögren's syndrome
Authors: Fox Robert I. , Bumol Thomas , Fantozzi Richard , Bone Robert , Schreiber Robert
Published: February 2007

Recent studies have suggested that the induction of HLA—DR antigens on epithelial cells plays an important role in the pathogenesis of autoimmune endocrine‐exocrine disorders. We found that salivary gland epithelial cells (i.e., acinar and ductal cells) in salivary gland biopsy specimens from patients with primary Sjögren's syndrome (keratoconjunctivitis sicca) expressed high levels of HLA—DR antigen, which were detected by staining frozen tissue sections with monoclonal antibodies and immunoperoxidase technique. In contrast, salivary gland epithelial cells from normal subjects did not express this antigen. Lymphocytes eluted from the salivary gland biopsy specimens of patients who had Sjögren's syndrome produced a soluble factor that stimulated HLA—DR synthesis by a salivary gland‐derived cell line (Sal‐1). These tissue culture supernatants contained γ‐interferon, and their ability to induce HLA—DR synthesis was blocked by monoclonal anti‐γ‐interferon antibody. These results demonstrate the presence of HLA—DR antigen on salivary gland epithelial cells and suggest that local production of γ‐interferon plays a role in this induction.
Neutral proteases in human osteoarthritic synovium
Authors: Martel‐Pelletier J. , Cloutier J. M. , Pelletier J. P.
Published: February 2007

The activities of neutral collagenolytic enyzmes (CE) and neutral proteoglycan‐degrading enzymes (PE) in the synovial membranes of osteoarthritis (OA) patients were determined. The total neutral metallo‐CE activity showed a significantly higher level of activity when the membranes of OA patients were compared with those of controls. The severely and moderately inflamed synovia had significantly more enzyme activity than did either mildly inflamed or control synovia. Steroids reduced the total metallo‐CE activity. In specimens with severe inflammation, the active form of the neutral metallo‐CE was significantly elevated over that found in controls. The serine‐CE activity was also significantly elevated in OA synovia with severe inflammation and synovial hypertrophy. The total and active neutral metallo‐PE was significantly elevated in synovial membranes of OA patients with severe inflammation. Moreover, the serine‐PE showed much more activity in OA patients than in controls. The enzyme activity remained at a significantly high level in the OA synovium, regardless of the presence or absence of macroscopic synovial hypertrophy or the histologic grading of the synovium (mild, moderate, severe). Our data indicate that, in OA, an increased level of neutral proteases in the synovia could be involved in the local tissue destruction of the periarticular structures. Because of the very high level of serine proteases, their diffusion may render plausible a degradative action on the cartilage surface.
Macrophage activation in rat models of inflammation and arthritis: Systemic activation precedes arthritis induction and progression
Authors: Johnson William J. , Muirhead Katharine A. , Meunier Paul C. , Votta Bart J. , Schmitt Thomas C. , Dimartino Michael J. , Hanna Nabil
Published: February 2007

The association between the induction and progression of adjuvant‐induced arthritis (AA) and the development of synovial and systemic macrophage activation was assessed by studying the temporal development of these parameters in a rat model. Rats with AA developed significant edema of the uninjected hind leg beginning 10 days post‐adjuvant injection, with progressive increases in edema continuing through day 17. Several parameters of macrophage activation, including the enhanced ability to secrete interleukin‐1 and prostaglandin E2, kill tumor cells, accumulate fluorescent cyanine dyes, emigrate into the peritoneal cavity and synovium, and express Ia antigen, as well as the decreased ability to secrete superoxide anion, were associated temporally with the development of the arthritic lesion. In addition to the temporal association between macrophage activation and development of arthritis, a positive correlation between macrophage activation and arthritis induction was seen with the use of synthetic adjuvants at arthritogenic and nonarthritogenic doses. These data taken together suggest that induction and progression of AA in rats is associated with both systemic (blood, spleen, and peritoneal cavity) and local (synovium) macrophage activation.