bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporomandibular joint involvement in systemic lupus erythematosus
Authors: Jonsson Roland , Lindvall Ann‐Marie , Nyberg Gudrun
Published: February 2007

Temporomandibular joint involvement was studied in 37 systemic lupus erythematosus patients not selected with regard to this involvement. One‐third had current complaints and two‐thirds had a history of severe symptoms. Objective findings indicating systemic lupus erythematosus arthritis were locking or dislocation, tenderness to palpation, and pain on movement of the mandible. Such changes were found in 8 patients (22%) but in none of the healthy controls. Radiographic changes of the condyles, including flattenings, erosions, osteophytes, and sclerosis, were seen in 11 patients (30%), 4 of whom had deformity of other joints as well.
Computed tomography and conventional radiographs of the craniocervical region in rheumatoid arthritis
Authors: Braunstein Ethan M. , Weissman Barbara N. , Seltzer Steven E. , Leland Sosman J. , Wang Ay‐Ming , Zamani Amir
Published: February 2007

Radiographs and computed tomography (CT) scans of 12 patients with rheumatoid arthritis of the cervical spine were reviewed to determine whether CT provides additional information to that obtained from conventional radiography and tomography. Modalities were compared with respect to determination of the extent of erosion, C1‐C2 subluxation, atlantoaxial impact impaction, and soft tissue findings. CT showed greater extent of erosion in 9 of 12 patients. In 11 patients with C1‐C2 subluxation, CT and plain radiographs were both useful because it was necessary to demonstrate both sagittal and axial relationships. In the 5 patients with atlantoaxial impaction both CT and plain radiographs demonstrated the abnormal relationships between the odontoid and the foramen magnum. CT showed attenuation of the transverse ligament and the presence or absence of spinal cord compression, whereas plain radiographs did not. Nevertheless, significant new information regarding the spinal cord was obtained by CT in only 1 of the 12 patients. Computed tomography provides additional information about the rheumatoid cervical spine that is unobtainable by conventional modalities. In particular, CT demonstrates bone changes in the axial projection and facilitates evaluation of soft tissue, ligament, and spinal cord involvement. However, CT should be reserved for those instances in which plain radiographs and tomograms do not explain clinical findings.
Biochemical and metabolic abnormalities in normal and osteoarthritic human articular cartilage
Authors: Ryu Junnosuke , Treadwell Benjamin V. , Mankin Henry J.
Published: February 2007

Incorporation of radioactive precursors into macromolecules was studied with human normal and osteoarthritic articular cartilage organ culture. Analysis of the salt extracted matrix components separated by cesium chloride buoyant density gradient centrifugation showed an increase in the specific activities of all gradient fractions prepared from the osteoarthritic cartilage. Further analysis of these fractions showed the osteoarthritic cartilage contained 5 times as much sulfate incorporated into proteoglycans, and an even greater amount of 3H‐glucosamine incorporated into material sedimenting to the middle of the gradient. Greater than half of this radioactive middle fraction appears to be hyaluronate, as judged by the position it elutes from a DEAE column and its susceptibility to hyaluronidase digestion. This study supports earlier findings showing increased rates of macromolecular synthesis in osteoarthritis, and in addition, an even greater synthetic rate for hyaluronic acid is demonstrated.
Ntp pyrophosphohydrolase in human chondrocalcinotic and osteoarthritic cartilage: some biochemical characteristic
Authors: Muniz Ofelia , Pelletier Jean‐Pierre , Martel‐Pelletier Johanne , Morales Sara , Howell David S.
Published: February 2007

Nucleoside triphosphate pyrophosphohydrolase activity was first detected in articular cartilage in previous studies at our laboratory. In this report, the enzyme is partially characterized with respect to its pH optimum and Km. The enzyme was metal‐dependent and was active in the presence of 1 mM Ca++. It was inhibited by several substances, including cysteine and dithiothreitol. Its activity was not inhibited by tetramisole at concentrations which inhibited 100% of the pyrophosphatase activity in the same extracts. It functioned most effectively on ATP, but also on UTP, CTP, and GTP. A role for scavenging nucleotides and production of pyro‐phosphate in osteoarthritic and chondrocalcinotic cartilage is postulated.
Studies on the kinetics of binding of complement‐fixing dsdna/anti‐dsdna immune complexes to the red blood cells of normal individuals and patients with systemic lupus erythematosus
Authors: Horgan Carol , Taylor Ronald P.
Published: February 2007

The kinetics of binding of prepared complement opsonized 3H‐dsDNA/anti‐DNA immune complexes to normal red blood cells (RBCs) and to RBCs with lowered immune complex binding capacity from certain patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis was examined. Normal RBCs bound the immune complexes rapidly and reached equilibrium in about 4 minutes at 37°C, while the SLE RBCs not only bound less immune complex but required up to 30 minutes to reach equilibrium. Chemical modification of normal RBCs with moderate amounts of dithiothreitol, an agent that destroys the binding activity of the C3b receptor (CR1), produced RBCs that mimicked the equilibrium and kinetic binding properties of the SLE RBCs. These observations, taken in conjunction with a detailed examination of the temperature dependence of the binding kinetics, suggest that CR1 reorganization on the RBC surface to form binding clusters may be an essential step in the complement mediated binding of immune complexes to RBCs. The implications of these findings with respect to the clearance of immune complexes from the circulation of patients with autoimmune diseases are discussed.
Clearance of 85Sr‐Labeled Calcium Phosphate Crystals from Rabbit Joints
Authors: Palmer David W. , Mccarty Daniel J.
Published: February 2007

The clearance of basic calcium phosphate crystals from rabbit joints was studied using synthetic crystals with characteristics similar to natural joint fluid mineral phase. Addition of strontium 85 during synthesis resulted in uniform trace‐labeling. Crystals were rapidly taken up by synovial lining cells after intrasynovial injection. The time for clearance of one‐half of the injected basic calcium phosphate crystal mass was 6.7 days, approximately 3 times faster than found previously for the much larger calcium pyrophosphate dihydrate crystals.
The lubricating activity of human synovial fluids
Authors: Swann David A. , Bloch Kurt J. , Swindell David , Shore Elizabeth
Published: February 2007

The lubricating abilities of human synovial fluids were measured using a rotating cartilage‐on‐glass apparatus. A total of 247 human fluids were lubricationtested. Of these, 20 of the 180 knee fluids from patients with degenerative/traumatic joint disease lubricated less well than normal bovine synovial fluid. The remainder of the fluids from the knee and other joints were equivalent to normal bovine synovial fluid in their lubricating properties. The concentrations of hyaluronic acid, protein, and sialic acid and the relative viscosity of 117 human fluid samples were determined, but no relationships between the gross composition and the lubricating abilities were apparent.
Dr Antigens and Gold Toxicity in white rheumatoid arthritis patients
Authors: Barger Bruce O. , Acton Ronald T. , Koopman William J. , Alarcón Graciela S.
Published: February 2007

An increase in the frequency of DR3 in rheumatoid arthritis (RA) patients exhibiting toxic reactions to chrysotherapy has been reported in several studies of white patients. This study was designed to compare DR antigen frequencies in local white RA patients undergoing chrysotherapy with their response to treatment. The results from our sample of RA patients (n = 148) confirm the fact that there is increased frequency of DR3 in patients who develop toxic reactions to gold therapy, as reported in other studies of white patients. The DR3 increase was attributable to those gold‐treated patients who developed proteinuria, and was not observed in patients who developed skin toxicity. Interestingly, the associations were not as strong as those found in other reports. Only 21.1% of the patients with DR3 manifested toxic reactions overall, with only one‐third of the patients with proteinuria being DR3 positive. There was also an association of toxicity, albeit not significant, with a decreased frequency of DR2, which is consistent with the suggestion that this phenotype may protect against adverse reactions to gold treatment. These results suggest that while DR3 is significantly associated with adverse response to gold treatment, the relationship is not as strong as that previously reported. Explanation of these differences remains to be elucidated.
Mitogenic effects of hydroxyapatite and calcium pyrophosphate dihydrate crystals on cultured mammalian cells
Authors: Cheung Herman S. , Story Michael T. , Mccarty Daniel J.
Published: February 2007

Synthetic hydroxyapatite (HA) crystals in 1% serum stimulated 3H thymidine uptake into quiescent canine synovial fibroblasts and human foreskin fibroblast cultures, as did 10% serum. The onset of stimulation and peak uptake of thymidine after crystal addition were delayed by 2—3 hours as compared with the effects produced by 10% serum. Stimulation of 3H thymidine uptake was proportional to the serum concentration used. HA crystals (50 μg/ml) stimulated nuclide uptake at each serum concentration used. 3H thymidine uptake was also proportional to the dose of HA or calcium pyrophosphate dihydrate crystals, although larger doses of the latter crystal were required to produce equivalent effects. Not all particulates were effective mitogenic agents. Latex beads and diamond crystals had no effect. Monosodium urate crystals modestly stimulated and calcium urate crystals markedly stimulated nuclide uptake. The more complex crystals found in a naturally occurring condition (calcinosis) were as mitogenic as the pure synthetic HA. The synovial cell hyperplasia sometimes associated with crystals might be explained in part by their mitogenic activity.
Type ii collagen—induced arthritis in mice
Authors: Wooley Paul H. , Luthra Harvinder S. , Krco Christopher J. , Stuart John M. , David Chella S.
Published: February 2007

The passive transfer of high levels of anti‐type II collagen antibody from mice with type II collagen‐induced arthritis may transfer arthritis to syngeneic recipient animals. However, the transfer of either arthritogenic or sub‐arthritogenic doses of polyclonal anti‐type II collagen antibody, or non‐arthritogenic monoclonal anti‐type II collagen antibody may protect mice against the subsequent induction of arthritis by type II collagen. A protective effect was also observed in mice given free native type II collagen intravenously before the administration of collagen in an arthritogenic protocol.
Phosphorylation of proteoglycans from human articular cartilage by a camp‐dependent protein kinase
Authors: Anderson Roger S. , Schwartz Edith R.
Published: February 2007

Purified proteoglycan subunits from human articular, bovine articular and nasal cartilages, and a rat chondrosarcoma were phosphorylated in vitro by beef heart cAMP‐dependent protein kinase in the presence of γ32P‐ATP. In these experiments, a maximum of 1.7 moles of 32P were incorporated per mole of proteoglycan from human cartilage. Phosphorylation was dependent on the presence of cAMP. Analysis by autoradiography revealed that serine residues in the core protein of the proteoglycan were the sites of phosphorylation. Treatment of proteoglycan subunits with chondroitinase ABC and alkaline phosphatase prior to reaction with cAMP‐dependent protein kinase increased the incorporation of 32P by 12–30% when compared with untreated proteoglycans. These data indicate that proteoglycans in cartilage can be phosphorylated by cAMP‐dependent protein kinase.
Degradation of a chromogenic substrate by α2‐macroglobulin from plasma of patients with rheumatoid arthritis
Authors: Teodorescu Marius , Gaspar Alexandre , Spear Greg , Skosey John L. , Ganea Doina
Published: February 2007

We have shown previously that serum from patients with rheumatoid arthritis (RA) contains a polyclonal B cell activator that is associated with α2‐macroglobulin (α2M). Some biologic effects of this activator appear to be due to a trypsin‐like protease attached to α2M. Therefore, in the present study, we used an anti‐α2M antibody solid‐phase assay, with Chromozym‐Try as a substrate, to determine the level of α2M‐protease complexes in plasma α2M. We found higher levels of these complexes in RA patients than in 2 control groups. Since α2M‐protease complexes have been shown to induce RA‐like inflammation in experimental animals and to be produced by lymphoid cells, we speculate that they may be involved in the pathogenesis of RA. However, the role of the other cells or enzyme systems in the formation of these complexes has not yet been ruled out. Results of these investigations could lead to another link between activation of the immune system and joint inflammation.
D‐penicillamine in patients with rheumatoid arthritis serum levels, pharmacokinetic aspects, and correlation with clinical course and side effects
Authors: Muijsers A. O. , Van De Stadt R. J. , Henrichs A. M. A. , Ament H. J. W. , Van Der Korst J. K.
Published: February 2007

After administration of D‐penicillamine to patients with rheumatoid arthritis, measurements of serum level and urinary excretion showed half‐life times of 1.6 hours in the rapid phase and 4–6 days in the slow phase. The latter evidence suggests that tissue pooling occurs. With a dosage of 750 mg/day, basic serum levels of 100 μM are gradually reached. Serum D‐penicillamine levels were shown to be the same for patients who responded well to treatment, those who did not respond, and for patients who had adverse side effects as well as those who had none. Intestinal resorption decreased when D‐penicillamine was taken close to meals and was greatly reduced by iron preparations.
Clonally restricted anti‐igg antibodies in rheumatoid arthritis
Authors: Persselin Jay E. , Louie James S. , Stevens Ronald H.
Published: February 2007

Clonally restricted anti‐IgG antibodies were detected, by isoelectric focusing (IEF) and chromatofocusing techniques, in the sera of patients with rheumatoid arthritis (RA). Anti‐Fab antibodies were predominantly acidic proteins with isoelectric points of 4.5–6.5 and displayed restricted spectrotype patterns. Proteins reactive with the Fc portion of IgG showed polyclonal spectrotype patterns with alkaline pI of 7.5–9.0. A limited array of anti‐Fab spectrotypes was consistently detected in RA sera when analyzed by IEF on 6M urea gels. Additional anti‐Fab antibody bands were detected when the RA sera were dialyzed against 4–6M urea prior to IEF analysis, indicating that some anti‐Fab antibodies exist in a complexed form in serum. Under these dissociating conditions, anti‐Fab antibodies could also be detected in normal subjects, but the spectrotype patterns were more restricted than those in RA sera. Because anti‐Fab antibodies may regulate normal immune responses, the increased quantity of clonally restricted anti‐Fab antibodies in RA may indicate an abnormality of this immunoregulation.
Studies of anti‐f(ab')2 antibodies and possible immunologic control mechanisms in systemic lupus erythematosus
Authors: Silvestris Franco , Bankhurst Arthur D. , Searles Robert P. , Williams Ralph C.
Published: February 2007

Studies of anti‐DNA and anti‐F(ab')2 antibodies were performed by enzyme‐linked immunosorbent assay in 51 patients with systemic lupus erythematosus (SLE). Patients with severe, uncontrolled disease showed high levels of anti‐DNA and low levels of anti‐F(ab')2 antibodies. Patients with quiescent SLE usually showed high levels of anti‐F(ab')2 and low levels of anti‐DNA antibodies. Isolated anti‐F(ab')2 antibodies from autologous SLE remission serum or from the sera of unaffected siblings of SLE patients showed maximum inhibition in test systems using affinity‐purified SLE anti‐DNA antibodies reacting with single‐stranded DNA.
Reproducibility of multiple‐observer scoring of radiologic abnormalities in the hands and wrists of patients with rheumatoid arthritis
Authors: Sharp John T. , 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. , Young Donald Y.
Published: February 2007

Forty‐one coded radiographic films from 16 patients with rheumatoid arthritis were read by 13 observers, using 4 different methods for scoring abnormalities. Although absolute scores differed widely among individual observers, correlation coefficients were greater than 0.850 for approximately 2 of 3 comparisons. When films were ranked, using the median rank of all readers, 72% of individual ranks were within 10% of the median ranks. Among serial films on individual patients, 92% of comparisons between early and late films were interpreted as demonstrating progression of abnormalities when mean standardized scores showed an increase in scores of 15 units or greater. Films with lesser changes were interpreted inconsistently. This study shows good general agreement among readers in scoring radiologic abnormalities of hands and wrists, when applied to a film set showing a broad spectrum of severity, and defines the sensitivity of radiologic detection of disease progression.
Effects of L‐canavanine on t cells may explain the induction of systemic lupus erythematosus by alfalfa
Authors: Alcocer‐varela Jorge , Iglesias Antonio , Llorente Luis , Alarcón‐Segovia Donato
Published: February 2007

Alfalfa sprouts can induce systemic lupus erythematosus (SLE) in monkeys. This property of alfalfa sprouts has been attributed to their non‐protein amino acid constituent, L‐canavanine. Occurrence of autoimmune hemolytic anemia and exacerbation of SLE have been linked to ingestion of alfalfa tablets containing L‐canavanine. In this report we show that L‐canavanine has dose‐related effects in vitro on human immunoregulatory cells, which could explain its lupus‐inducing potential. These effects include: 1 diminution of the mitogenic response to both phytohemagglutinin and concanavalin A but not to pokeweed mitogen, as determined in both thymidine incorporation and cell cycle studies, and 2 abrogation of concanavalin A‐induced suppressor cell function, which results in increased release of both IgG and DNA binding activity into supernatants by cells from normal subjects and SLE patients. These immunoregulatory effects of L‐canavanine may explain the induction or exacerbation of SLE by alfalfa.
HLA gene frequencies in children and adults with systemic onset juvenile rheumatoid arthritis
Authors: Miller Marc L. , Aaron Stephen , Jackson Jean , Fraser Patricia , Cairns Lloyd , Hoch Susan , Borel Yves , Larson Martin , Glass David N.
Published: February 2007

The HLA genetic region was studied in 51 patients with systemic onset juvenile rheumatoid arthritis: 35 with childhood onset and 16 with adult onset (adult Still's disease). HLA genotypes were established by including family members, 261 of whom were also typed in the study. The most marked difference between patients and controls involved the HLA‐DR4 gene, which occurred with a frequency of 0.348 in the childhood onset patients and 0.170 in the controls (X2 = 8.97, P = 0.0028, adjusted P = 0.017). In contrast, the adult onset patients showed a marginal increase in HLA‐DR7, but were similar to controls with respect to HLA‐DR4. HLA‐Bw35 was increased in children with systemic onset disease, in accordance with earlier findings. The results suggest that patients with systemic onset juvenile rheumatoid arthritis have complex HLA associations which are different in childhood onset and adult onset disease.
Immunohistochemical studies of interleukin‐2 and γ‐interferon in rheumatoid arthritis
Authors: Husby Gunnar , Williams Ralph C.
Published: February 2007

Synovial tissues were studied, using immunofluorescence techniques, for localization of lymphocytic infiltrates and immune reactants, including C3, C5b‐9, C9, and la antigen. Tissue distribution of interleukin‐2 (IL‐2) and γ‐interferon was also determined, using mouse monoclonal antibodies. IL‐2 was found in association with OKT8 and OKT4 T cells, and γ‐interferon was noted in association with T cells, B cells, and macrophages. Staining both for IL‐2 and for γ‐interferon was surprisingly faint in view of the intensity of lymphocytic infiltration.
Substrain heterogeneity in prostaglandin E2 synthesis of human dermal fibroblasts. Differences in prostaglandin E2 synthetic capacity of substrains are not stimulus‐restricted
Authors: Korn Joseph H.
Published: February 2007

We examined prostaglandin E2 (PGE2) biosynthetic heterogeneity in fibroblast substrains and possible mechanisms that might mediate this heterogeneity. PGE2 synthesis of fibroblast substrains, in response to phytohemagglutinin‐stimulated mononuclear cell supernates, ranged from 9.0 ± 1.0 ng/ml to 79.3 ± 7.4 ng/ml (mean ± SD). The phenotypic behavior of individual substrains was stable. Substrains were also heterogeneous in PGE2 response to phorbol myristate acetate, and displayed stability in this phenotype as well. Substrains which were high responders to mononuclear cell supernate also ranked high in response to phorbol myristate acetate. Similar heterogeneity was observed in response to purified interleukin‐1. Arachidonic acid added exogenously did not raise interleukin‐1 responsiveness of low‐producer substrains to that of high producers, suggesting that differences in PGE2 synthesis among substrains did not reflect differences in substrate availability or phospholipase activity. Supernates of high‐ and low‐responder phenotype substrains, when added to cells of the reciprocal strain or to unrelated fibroblasts, did not affect the pattern of PGE2synthesis. The concordance of substrain responsiveness to mononuclear cell supernate and phorbol myristate acetate suggests that heterogeneity among substrains in PGE2 synthesis is related to the ability to produce PGE2 rather than to the ability to respond to a given mediator. In addition, differences in PGE2 synthesis among substrains do not appear to result from release of regulatory autokines.
Kinetics of Extraction of Proteoglycans from Human Cartilage
Authors: Pottenger Lawrence A. , Webb June E. , Lyon Nancy B.
Published: February 2007

Fifty‐one uniformly sliced human patellar cartilage specimens were extracted with physiologic buffer containing inhibitors. Galactosamine‐rich proteoglycans were more easily extracted than glucosamine‐rich proteoglycans. Extraction occurred in 2 phases. There was a large proteoglycan extraction during the first 30 minutes, followed by a steady loss proportional to the square root of time. The amount of proteoglycans extracted during phase 1 was approximately half that of phase 2. Extraction of proteoglycans varied with age, structural integrity, and cartilage thickness. Intact osteoarthritic cartilage had normal proteoglycan extraction.
Spontaneous in vitro production of anti‐DNA and anti‐RNA by systemic lupus erythematosus and normal peripheral blood mononuclear cells
Authors: Liebling Michael R. , Wong Curtice , Radosevich Jean
Published: February 2007

The spontaneous in vitro production of anti‐DNA and anti‐RNA by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE) and from normal subjects was evaluated employing sensitive solid‐phase assays that are specific for these antibodies. PBMC from SLE patients produced more IgG anti‐DNA and anti‐RNA than did normal PBMC (P < 0.01). In vitro production of IgG anti‐DNA appeared to correlate with serum DNA bindings (r = 0.72, P < 0.005). Similar amounts of IgM anti‐DNA and anti‐RNA were produced by both SLE and normal PBMC. However, IgM anti‐DNA antibodies always appeared to be directed against determinants on denatured DNA. Only PBMC from SLE patients produced IgG antibodies to native DNA.
Relationship between nailfold capillary abnormalities and organ involvement in systemic sclerosis
Authors: Lovy Michael , Mac‐Carter Daryl , Steigerwald James C.
Published: February 2007

Nailfold capillary abnormalities in 42 consecutive patients with systemic sclerosis were studied by widefield capillary microscopy, and capillary abnormalities were correlated with organ involvement. Twenty‐eight patients had diffuse skin disease, and 14 had the CREST variant of systemic sclerosis (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias) with anticentromere antibodies. Nailfold capillary enlargement and loss were graded from photographs. There was no correlation between the severity of either nailfold capillary loss or enlargement and duration of disease, number of organ systems involved, or acroosteolysis. The presence of telangiectasias correlated with extreme capillary enlargement (P < 0.025). Based on these findings it can be concluded that nailfold capillary changes in individual patients with systemic sclerosis are not useful in predicting organ involvement.
Reduced joint count indices in the evaluation of rheumatoid arthritis
Authors: Egger M. J. , Huth D. A. , Ward J. R. , Reading J. C. , Williams H. J.
Published: February 2007

Two types of summary measures of joint disease were evaluated in 2 controlled clinical trials in rheumatoid arthritis patients. One measure was based solely on the clinical/biologic judgment approach; the other combined this methodology with statistical approaches using reliability and factor analyses. „Signal joint”︁ indices, summarizing disease activity in 2–5 key joints, were found to be insensitive to deterioriation of nonsignal joints. Therefore, they are not recommended as replacements for the complete articular survey in rheumatoid arthritis. A reduced version of the complete articular survey was found to be desirable based on its validity, reliability, accuracy, precision, and sensitivity to active drugs. Its sensitivity can be slightly higher or lower than that of the full joint survey.
Effectiveness of cyclosporin therapy for Beh¸let's disease
Authors: Nussenblatt Robert B. , Palestine Alan G. , Chan Chi‐Chao , Mochizuki Manabu , Yancey Kim
Published: February 2007

Behçet's disease is a clinical entity with mouth and genital ulcers, skin lesions, and both anterior and posterior uveitis as its major criteria. It has been theorized that Behçet's disease is immune complex mediated, and is characterized by multiple attacks which often lead to severe visual handicap. Behçet's disease patients with severe ocular involvement and cytotoxic and/or systemic corticosteroid agent failures were treated with cyclosporin (CsA). CsA therapy effectively abrogated the acute phase of the ocular attack and either totally prevented, or markedly reduced, the recurrences of these attacks. Generally, patients tolerated the medication well; occasionally however, renal toxicity secondary to cyclosporin therapy prevented prescription of a maximally effective therapeutic dose of the drug. CsA levels in plasma were dose‐dependent for each patient, but the dosage per kg of CsA needed to obtain a specific plasma level varied greatly from patient to patient. Circulating immune complex levels were not universally elevated during the acute ocular attack. However, increases in circulating immune complex concentrations were noted after treatment with CsA was begun and the disease became clinically inactive. These data, as well as the effectiveness of CsA, an agent with predominantly anti–T cell effects, raise a question as to whether circulating immune complexes are centrally relevant to the pathogenesis of this disorder, and if T cell mediation of this disease must be contemplated.
Outcomes of self‐help education for patients with arthritis
Authors: Lorig Kate , Lubeck Deborah , Kraines R. Guy , Seleznick Mitchell , Holman Halsted R.
Published: February 2007

Behavioral and health status outcomes of an unreinforced, self‐help education program for arthritis patients taught by lay persons were examined in 2 ways: a 4‐month randomized experiment and a 20‐month longitudinal study. At 4 months, experimental subjects significantly exceeded control subjects in knowledge, recommended behaviors, and in lessened pain. These changes remained significant at 20 months. The course was inexpensive and well‐accepted by patients, physicians, and other health professionals.
Utilization of nonsteroidal antiinflammatory drugs
Authors: Baum Carlene , Kennedy Dianne L. , Forbes Mary B.
Published: February 2007

Information derived from pharmaceutical marketing databases on the use of 12 nonsteroidal antiinflammatory drugs in 1983 is presented. Estimates of population exposure, regularity of treatment, average daily dose, age and sex distributions of users, concomitant use of other drugs, associated diagnoses, and trends in use are provided. Utilization patterns were similar for 8 of the nonsteroidal antiinflammatory drugs, with differing patterns seen for mefenamic acid, oxyphenbutazone, phenylbutazone, and zomepirac.
Application, to Japanese patients, of the 1982 American Rheumatism Association revised criteria for the classification of systemic lupus erythematosus
Authors: Yokohari Ryuichi , Tsunematsu Tokugoro
Published: February 2007

The 1982 American Rheumatism Association revised criteria for the classification of systemic lupus erythematosus were tested on Japanese patients. Sensitivity and specificity data were comparable with those presented in the development of the revised criteria by the American Rheumatism Association. Complement determinations were evaluated for their ability to improve the criteria for the diagnosis of early systemic lupus erythematosus.
Influence of the severity and duration of murine antigen‐induced arthritis on cartilage proteoglycan synthesis and chondrocyte death
Authors: Kruijsen Marijn W. M. , van den Berg Wim B. , van de Putte Levinus B. A.
Published: February 2007

Recent studies have shown that joint inflammation can suppress chondrocyte proteoglycan synthesis and can even kill chondrocytes. In the present study, we investigated the influence of the severity and chronicity of murine antigen‐induced arthritis on the degree of these toxic effects on chondrocytes. Joint inflammation, quantitated by measurements of 99mtechnetium pertechnetate uptake, was significantly correlated with the inhibition of proteoglycan synthesis, measured by 35S‐sulfate incorporation. Histologic grading of the extent of chondrocyte death on day 28 after arthritis induction correlated best with the degree of inflammation present on day 14. High scores for chondrocyte death were found only in mice with persistent, severe arthritis. Our data indicate that the severity of joint inflammation is a major determinant of the degree of chondrocyte proteoglycan synthesis inhibition, whereas both the severity and chronicity of the inflammation determine chondrocyte killing and, therefore, irreversible joint destruction.
Impact of diagnosis‐related group‐based reimbursement for treatment of rheumatic diseases in a teaching hospital
Authors: Hartley Robert M. , Liang Matthew H. , Cullen Karen E.
Published: February 2007

The impact of Medicare's diagnosis‐related group (DRG)‐based reimbursement system was examined for care given to 734 rheumatic disease patients discharged from a teaching hospital during a 2‐year period. The analysis accounted for length of stay “outliers” as defined by Medicare and distinguished costs from charges. Excluding outliers, DRG reimbursement would result in net revenues to the hospital of $1,126 per DRG 240 patient and $1, 794 per DRG 241 patient. The difference between DRGs in cost per patient was significant, indicating that DRGs clearly identify 2 groups of rheumatic disease patients. After excluding outliers, the coefficients of variation in costs for DRGs 240 and 241 were 72% and 80%, respectively, which although high, were average for DRGs at our institution. Mean total charge per patient was different for groups defined by their primary rheumatologic diagnosis in DRG 240 but not DRG 241. For rheumatoid arthritis and systemic lupus erythematosus patients, the total charge per patient did not differ, but the types of services did. The cost of treating outliers would create an average loss per outlier of $18,400 and $16,500, respectively, in DRGs 240 and 241. Outliers accounted for 34.5% and 21.8% of the 2 DRGs' total costs, respectively, but only 6.4% and 3.6% of the total number of patients. Under current DRG reimbursement rates, the cost of care for rheumatology patients would be adequately reimbursed in our hospital: losses from outliers would be offset by net revenues from inliers as long as current Medicare adjustments for capital and medical education costs were continued.
The value of complement and immune complex determinations in monitoring disease activity in patients with systemic lupus erythematosus
Authors: Valentijn R. M. , van Overhagen H. , Hazevoet H. M. , Hermans J. , Cats A. , Daha M. R. , van Es L. A.
Published: February 2007

Serial serum samples from 33 patients with systemic lupus erythematosus were tested for CH50, C3, C4, and circulating immune complexes. Circulating immune complexes were determined by 5 different assays. Disease activity was determined by a scoring system we devised. On an interpatient analysis, overall disease activity correlated significantly with levels of CH50, C3, and a positive result on C1q binding assay. However, with the exception of depressed C3 levels, the sensitivity, specificity, and predictive values of all the serologic tests were low. An intrapatient analysis revealed a patient‐specific activity parameter in 11 of the 33 patients. We conclude that these serologic tests are not reliable in assessing disease activity in patients with systemic lupus erythematosus, although a small subgroup of patients will exhibit a patient‐specific activity parameter.
A rheumatoid arthritis b cell subset expresses a phenotype similar to that in chronic lymphocytic leukemia
Authors: Plater‐Zyberk C. , Maini R. N. , Lam K. , Kennedy T. D. , Janossy G.
Published: February 2007

An abnormal subpopulation of B cells expressing the T1 antigen, which is normally restricted to T cells, was demonstrated in the peripheral blood of 16 patients with rheumatoid arthritis. This T1+ B cell population accounted for a mean of 19.6% (upper limit 48%) of the circulating B cells and did not correlate with clinical disease activity, rheumatoid factor, or drug treatment. The highest percentage of T1+ B cells found in the blood of 8 patients with connective tissue diseases, including systemic lupus erythematosus, was 5% of the B cells, and for normal controls, it was was 3% of the B cells. As previously reported, we confirmed that the T1+, Ig+ phenotype was a feature of leukemic cells in B‐type chronic lymphocytic leukemia. The finding of increased numbers of T1+ B cells in patients with rheumatoid arthritis and those with B‐type chronic lymphocytic leukemia raises the possibility that these cells play a role in a spectrum of diseases, including those involving autoimmunity and malignancy.
Total lymphoid irradiation in patients with refractory rheumatoid arthritis
Authors: Nüsslein Hubert G. , Herbst Manfred , Manger Bernhard J. , Gramatzki Martin , Burmester Gerd R. , Fritz Harald , Sauer Rolf , Kalden Joachim R.
Published: February 2007

Eleven patients with rheumatoid arthritis that had been refractory to conventional drug therapy were treated with total lymphoid irradiation (TLI). Followup continued for 6 months in 9 patients, 12 months in 6 patients, and 24 months in 3 patients. At 6 and 12 months post‐TLI, a significant improvement in clinical disease activity was demonstrated. Side effects noted during TLI included fatigue, nausea, diarrhea, and vomiting. One patient died of cardiorespiratory arrest, 2 patients died of kidney failure secondary to generalized amyloidosis, and 1 patient died of septic shock secondary to a multilocular septic arthritis. One patient experienced 2 episodes of septic arthritis; 2 patients manifested delayed wound healing. Immunologic assessments showed consistent lymphopenia in all patients. T lymphocyte subsets decreased after TLI, and showed a transient increase at 6 months post‐TLI. The suppressed mitogen responsiveness, which was noted 2 months after irradiation, was found to increase almost to the pre‐TLI levels at 12 months. The observed increase in morbidity and mortality after TLI is evidence that discourages the use of this therapeutic technique, at least in its present form.
Ro (SS‐A) antibody and antigen in a patient with congenital complete heart block
Authors: Harley John B. , Kaine Jeffrey L. , Fox Owen F. , Reichlin Morris , Gruber Barry
Published: February 2007

Congenital complete heart block is closely associated with the presence of anti‐Ro (SS‐A) autoantibodies. Quantitative solid‐phase assays for Ro (SS‐A) autoantigen and autoantibody have established the presence of Ro (SS‐A) in cardiac tissues and have been used to evaluate an informative pedigree. The propositus we describe here had complete congenital heart block and showed anti–Ro (SS‐A) binding of 13‐fold less than his normal HLA‐identical twin sister. Both had identical titers of antinuclear antibody. These data support the hypothesis that anti–Ro (SS‐A) may be directly involved in the pathogenesis of congenital complete heart block.
Effects of gold sodium thiomalate on functional correlates of human monocyte maturation
Authors: Littman Bruce H. , Hall Robert E.
Published: February 2007

The mechanism of action of gold salts in the treatment of rheumatoid arthritis is unknown. Effects of gold on monocyte‐macrophage function could be due to inhibition of maturation and differentiation. We found that 3 markers of monocyte differentiation, loss of peroxidase activity, spontaneous synthesis of C2, and spontaneous cytotoxicity for chicken erythrocytes, were all inhibited by gold treatment. This was not a general toxic effect since phorbol myristate acetate could still induce gold‐treated monocytes to lyse chicken erythrocytes. Also, phorbol myristate acetate‐stimulated superoxide production, a monocyte function not requiring further differentiation, was not inhibited by incubation with gold. Lymphokine‐stimulated cytotoxicity for nucleated target cells, another function of monocytes, was inhibited only partially for certain target cells and not at all for others. These data suggest that gold has the capacity to selectively inhibit some monocyte functions which are associated with macrophage differentiation.
Persistence of scleroderma‐like phenotype in normal fibroblasts after prolonged exposure to soluble mediators from mononuclear cells
Authors: Worrall Jennifer G. , Whiteside Theresa L. , Prince Robert K. , Buckingham Robert B. , Stachura Irene , Rodnan Gerald P.
Published: February 2007

Supernatants of mononuclear cells (MNC‐SN) were shown to increase synthesis of glycosaminoglycan (GAG) by cultured normal dermal fibroblasts. Fibro‐blasts from the skin of patients with progressive systemic sclerosis (PSS, scleroderma) were hyporesponsive. We exposed fibroblasts outgrowing from explants of normal adult skin to MNC‐SN for up to 30 generations in culture. MNC‐SN were obtained by incubating normal MNC with concanavalin A. Four experimental, 4 normal control, and 3 PSS control lines were passaged by trypsinizing and splitting the cultures 1:2 every 7 days. At the third and fifth passages, portions of the experimental fibroblasts were removed from MNC‐SN, then passaged in medium alone. Cell counts, assays for GAG, and electron microscopy were performed and increases in GAG after brief reexposure to MNC‐SN were determined at the third, fifth, and eighth passages. In normal dermal fibroblasts, baseline GAG production, measured by 3H‐glucosamine uptake, was low and increased as much as 15 times after reexposure to MNC‐SN. In contrast, production was high in both experimental and PSS lines, and increases after reexposure to MNC‐SN were consistently small. This PSS‐like behavior persisted in experimental fibroblasts removed from MNC‐SN at the third and fifth passages. Growth of experimental and scleroderma fibroblasts was slower than that of control fibroblasts. Ultra‐structurally, both scleroderma and experimental dermal fibroblasts differed from normal fibroblasts by their oval cellular shape, indentations in nuclear membrane, numerous organelles and bundles of microfilaments, prominent Golgi, and intranuclear inclusions. These experiments indicate that normal adult dermal fibroblasts subjected to MNC‐SN in vitro acquire a scleroderma‐like phenotype that persists for many generations.
Hereditary joint disorder in progressive ankylosis (ank/ank) mice. II. Effect of high‐dose hydrocortisone treatment on inflammation and intraarticular calcium hydroxyapatite deposits
Authors: Hakim Frances T. , Brown Kenneth S. , Oppenheim Joost J.
Published: February 2007

Mice homozygous for the progressive ankylosis trait develop an inflammatory joint disorder associated with the intraarticular deposition of calcium hydroxyapatite. When affected (ank/ank) mice were treated with high doses of hydrocortisone, synovitis receded, development of cartilaginous and bony osteophytes halted, and calcium hydroxyapatite accumulated in and distended the synovial spaces. No changes, however, occurred in the joint morphology of hydrocortisonetreated normal (ank/+) mice. Since inhibition of inflammation by hydrocortisone treatment did not block apatite accumulation, intraarticular deposition of hydroxyapatite occurs independent of inflammation in progressive ankylosis.
Histamine stimulates prostaglandin E production by rheumatoid synovial cells and human articular chondrocytes in culture
Authors: Taylor David J. , Yoffe Joan R. , Brown Diane M. , Woolley David E.
Published: February 2007

Histamine stimulates prostaglandin E (PGE) production by cultures of adherent rheumatoid synovial cells and human articular chondrocytes. When subcultured synovial fibroblasts or human articular chondrocytes were “primed” by preincubation with conditioned media from primary adherent rheumatoid synovial cell cultures (synovial factor), each produced even higher PGE levels upon histamine exposure. This histamine stimulation was prevented by histamine H1, but not H2, antagonists and was more marked if serum was absent from the culture media. Thus, histamine‐induced PGE production by these cells is mediated via H1 receptor activation and subsequent arachidonic acid liberation.
Phagocytosis and intracellular killing of Staphylococcus aureus by polymorphonuclear cells from synovial fluid of patients with rheumatoid arthritis
Authors: Breedveld Ferdinand C. , Lafeber Geertruida J. M. , van den Barselaar Maria T. , van Dissel Jaap T. , Leijh Peter C. J.
Published: February 2007

The phagocytosis and intracellular killing by synovial fluid (SF) polymorphonuclear cells (PMN) of 10 patients with rheumatoid arthritis was studied. PMN phagocytosis was assessed by morphologic and microbiologic methods and intracellular killing was measured independently of continuous phagocytosis of Staphylococcus aureus. Phagocytosis of S aureus by SF PMN or peripheral blood (PB) PMN was as effective in the presence of synovial fluid as in the presence of serum. On average, SF PMN ingested S aureus opsonized with synovial fluid and serum more efficiently than patient or donor PB PMN did. Enhanced ingestion of S aureus was associated with increased expression of C3 receptors on the membrane of SF PMN. In the presence of heat‐inactivated synovial fluid, the capacity of SF PMN to ingest S aureus was greater than that of patient or donor PB PMN. Under these conditions, phagocytic activity was correlated with Fc receptor expression. SF PMN was found to be as active in killing S aureus as PB PMN from healthy donors.
Type C retroviruses of the human T cell leukemia family are not evident in patients with systemic lupus erythematosus
Authors: Boumpas D. T. , Popovic M. , Mann D. L. , Balow J. E. , Tsokos G. C.
Published: February 2007

Type C retroviruses of the human T cell leukemia virus (HTLV) family have been implicated in immune aberrations observed in patients with leukemias, lymphomas, and the acquired immune deficiency syndrome. We have investigated whether retroviruses of the HTLV family are involved in the etiopathogenesis of systemic lupus erythematosus (SLE) by using 1) an immunoenzymatic assay to measure antibodies to HTLV‐I and HTLV‐III proteins in the sera of 30 patients with SLE, and 2) nucleic acid hybridization techniques (Southern transfer) to detect proviral sequences of HTLV‐I, HTLV‐II, and HTLV‐III in DNA extracted from peripheral blood mononuclear cells of 10 of these patients. Sera from 20 normal individuals served as controls. None of the 30 sera from SLE patients or the 20 sera from normal controls had any detectable antibodies to HTLV‐I or HTLV‐III. Nucleic acid hybridization studies also failed to detect any HTLV proviral sequences. These results suggest that viruses of the HTLV family do not participate in the etiopathogenesis of SLE.
Inhibition by cyclosporin A of streptococcal cell wall‐induced arthritis and hepatic granulomas in rats
Authors: Yocum David E. , Allen Janice B. , Wahl Sharon M. , Calandra Gary B. , Wilder Ronald L.
Published: February 2007

We investigated the effect of cyclosporin A, an inhibitor of T helper/inducer lymphocyte activation, on the development of streptococcal cell wall‐induced arthritis and hepatic granulomas in female LEW/N rats. Continuous daily treatment with cyclosporin A, begun either 24 hours before or 7–12 days after streptococcal cell wall administration and continued for 6 weeks, resulted in significant inhibition of the chronic proliferative, erosive synovitis and total inhibition of hepatic granuloma formation. When cyclosporin A was stopped at 6 weeks, its effects continued for at least another 5 weeks, demonstrating long‐term benefit without continued administration of the drug. In contrast, therapy given only during the acute phases of the experimental disease (days 1–12) did not inhibit the development of chronic disease. Cyclosporin A had no apparent effects on streptococcal cell wall antigen distribution or persistence in tissues. These data provide additional evidence of an important role for the T helper/inducer lymphocyte in the experimental model and suggest that cyclosporin A may be a useful probe in defining molecular and cellular processes involved in chronic proliferative and erosive synovitis.
Immunoglobulin from systemic lupus erythematosus serum induces interferon release by normal mononuclear cells
Authors: Ramirez Francisco , Williams Ralph C. , Sibbitt Wilmer L. , Searles Robert P.
Published: February 2007

Ig fractions from patients with systemic lupus erythematosus (SLE) were tested with cultured normal peripheral blood mononuclear cells for induction of interferon release. Lymphocyte eluates, euglobulins containing IgG and IgM, and IgG or IgM from DEAE or sucrose gradients all induced interferon production. Lymphocytotoxic antibody in SLE sera showed a high correlation with capacity of isolated Ig fractions to induce interferon. Most interferon produced was of the gamma type. Monoclonal SLE IgM antilymphocyte antibody induced interferon synthesis.