bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of native and denatured DNA antibody forming cells by the enzyme‐linked immunospot assay: A clinical study of (New Zealand black × New Zealand white)F1 mice
Authors: Ando Dale G. , Ebling Fanny M. , Hahn Bevra H.
Published: February 2007

A new method for measuring DNA antibody forming cells (DNA‐AFC) using the enzyme‐linked immunospot (ELISPOT) assay is described. This method uses enzyme‐linked immunosorbent assay (ELISA) techniques applied to cells cultured on DNA‐coated plates, which allows visual quantitation of spots representing imprints of specific antibodies from DNA‐AFC. Specificity for DNA was confirmed by inhibition studies and lack of reactivity by anti‐lysozyme hybridomas. Isotypes of IgG and IgM can be measured using the appropriate antisera in the assay. A study of 16 female (New Zealand black × New Zealand white)F1 ([NZB × NZW]F1) female mice showed significant correlation between age, rising blood urea nitrogen levels, and increasing proteinuria and increasing numbers of DNA‐AFC. In contrast, the correlation between circulating antibodies to DNA (ELISA method) and clinical parameters of nephritis was not significant. Both the native DNA ELISPOT and the native DNA ELISA had similar significant linear correlations with age. This is the first report of use of the ELISPOT assay for measurement of DNA‐AFC. The DNA‐AFC measured by this method were specific and correlated with the presence of clinical nephritis in (NZB × NZW)F1 mice. This method should allow further study on the regulation of DNA‐AFC in vitro and in vivo, and will be useful in the investigation of DNA‐AFC and cellular mechanisms of autoimmunity.
Eosinophilic synovitis: Clinical observations on A newly recognized subset of patients with dermatographism
Authors: Brown Jacques P. , Rola‐Pleszczynski Marek , Menard Henri‐A.
Published: February 2007

Eosinophilia of synovial fluid is uncommon. Using the identification of Charcot‐Leyden crystals to alert for the presence of eosinophils, we have increased by a factor of 5 the detection rate of synovial fluid eosinophilia. We describe here our clinical and laboratory findings in 7 patients with this feature. We believe they constitute a defined syndrome. Typically, the patients were young (ages 18–51) and had a personal and family history of allergy. They developed an acute, painless monarthritis after a minor trauma, and had no concurrent allergic symptoms. Each episode resolved in 1–2 weeks without therapy, and 3 patients had recurrences. All had pronounced dermatographism. The synovial fluid was mildly inflammatory: 10,850 ± 3,665 white blood cells/mm3, with 41 ± 5% eosinophils (mean ± SEM). The cellularity and chemistry of the peripheral blood was unremarkable, except for a mild elevation of IgE levels (370 ± 104 IU/ml). The exact pathophysiologic mechanism underlying this benign entity is not clear, but we suspect a nonimmunologic triggering event is operant, i.e., synovial trauma which mimics the cutaneous dermatographism.
Intraarticular ferritin‐bound iron in rheumatoid arthritis: A factor that increases oxygen free radical‐induced tissue destruction
Authors: Biemond Pieter , Swaak Antonius J. G. , Van Eijk Henk G. , Koster Johan F.
Published: February 2007

Iron mobilized from ferritin is able to convert superoxide and hydrogen peroxide, which are produced in large amounts in rheumatoid arthritis (RA), to the extremely toxic hydroxyl radical. We have found that synovial fluid ferritin is increased significantly in RA patients compared with levels in controls. The high synovial fluid:serum ferritin ratio is compatible with the hypothesis that synovial fluid ferritin is derived from the synovial membrane. We found no difference in ferritin concentrations in the synovial membranes of RA patients compared with those of controls. Quantitative data on the amount of iron bound to ferritin showed that the level was 2.9 times higher in RA synovial membranes than in those of controls. Moreover, RA synovial fluid contained considerable amounts of iron bound to ferritin. Calculation of the iron saturation of ferritin revealed that RA synovial membranes contained a mean of 2,210 moles of iron per mole of ferritin: a significant elevation when compared with the mean value of 1,500 moles found in the synovial membranes of the controls. The decreased saturation of ferritin in RA synovial fluid, compared with that in the synovial membrane, could be caused by an uncompensated release of iron from ferritin, which has been induced by superoxide that is produced by stimulated granulocytes. The results demonstrate that in the joints of RA patients, sufficient ferritin loaded with iron is available to stimulate oxygen free radical damage.
Group therapies for rheumatoid arthritis: A controlled study of two approaches
Authors: Strauss Gordon D. , Spiegel Jane Sinden , Daniels Marcia , Spiegel Timothy , Landsverk John , Roy‐Byrne Peter , Edelstein Carole , Ehlhardt Johanna , Falke Roberta , Hindin Lee , Zackler Les
Published: February 2007

An important unanswered question about rheumatoid arthritis (RA) is how the patient's psychological or emotional state relates to disease activity and functional status. No controlled studies of psychothera‐peutic interventions in RA have been reported. To test the hypothesis that a psychosocial intervention would lead to improvement in functional status or disease activity, 57 RA patients were randomly assigned to 1 of 3 groups, which received: 1) conventional group psychotherapy; 2) group assertion/relaxation training; or 3) no treatment (control group). Patient and physician questionnaires collected at baseline, immediately after the interventions, and 12 months after baseline provided outcome data on functional status, social and psychological adaptation, psychological symptoms, and disease activity. There were few outcome measures for which either treatment resulted in significantly higher scores than were seen in controls, though more improvement did occur among patients who received conventional group psychotherapy.
Deficient γ‐interferon production in patients with systemic lupus erythematosus
Authors: Tsokos George C. , Boumpas Dimitri T. , Smith Paula L. , Djeu Julie Y. , Balow James E. , Rook Alain H.
Published: February 2007

We examined the ability of peripheral mononuclear cells (MNC) from patients with systemic lupus erythematosus (SLE) to produce γ‐interferon (γ‐IFN) in vitro. MNC from patients with SLE produced varying amounts of γ‐IFN upon mitogenic stimulation. However, they produced distinctly decreased amounts of γ‐IFN upon in vitro stimulation with interleukin‐2 (IL‐2). Deficient production seemed to be primary, rather than secondary to either excessive monocytic suppresion or failure of IL‐2 to bind to the MNC surface membranes. γ‐IFN‐specific RNA transcription, as determined by slot‐blot analysis, was severely decreased in MNC that had been stimulated with phytohemag‐glutinin or IL‐2. These findings suggest that MNC of patients with SLE have defects in the IL‐2 signal transduction which is required for production of γ‐IFN.
DNA‐daunorubicin complexes specifically suppress in vitro spontaneous anti‐DNA antibody production in lymphocytes of patients with systemic lupus erythematosus
Authors: Takeuchi Tsutomu , Koide Jun , Hosono Osamu , Amano Koichi , Homma Mitsuo , Masuho Yasuhiko , Morimoto Chikao , Takano Makoto , Abe Tohru
Published: February 2007

Elevated production of anti‐DNA antibody in patients with systemic lupus erythematosus (SLE) is a central problem in the pathogenesis of tissue injury. In the present study, we attempted to manipulate anti‐DNA antibody production through the antigen‐cytotoxic drug conjugates, DNA‐daunorubicin complexes. The effect of DNA‐daunorubicin complexes was determined by examining SLE lymphocytes for spontaneous in vitro production of anti‐DNA antibody. These complexes, at 2 μg/ml, suppressed anti‐DNA antibody production, but not total IgG production, which suggests that specific suppression of anti‐DNA antibody production was achieved at this concentration. We believe that the DNA‐daunorubicin complexes affected mainly B cells, since such suppression was obtained by treating B cells, as well as B plus T cells. Furthermore, the complexes had no effect on the proliferative responses of SLE T cells to DNA, phytohemagglutinin, or concanavalin A. These results indicate that DNA‐daunorubicin complexes may have the potential for selectively suppressing anti‐DNA antibody production in patients with SLE.
Evidence of an immunopathogenic basis for central nervous system disease in primary Sjögren's syndrome
Authors: Alexander Elaine L. , Lijewski Jane E. , Jerdan Myles S. , Alexander Garrett E.
Published: February 2007

The pathogenesis of central nervous system complications in primary Sjögren's syndrome (CNS‐SS) is unknown. In order to determine whether patients with active CNS‐SS have cerebrospinal fluid (CSF) abnormalities indicative of CNS inflammation, CSF analyses from 30 patients with active CNS‐SS (SSA) were contrasted with those from 20 SS patients without CNS involvement (SSI) and 20 patients with systemic lupus erythematosus and active CNS disease (SLEA). Elevations of total protein concentration, IgG concentration, IgG to total protein ratio, and IgG index were observed in patients with SSA, but not in those with SSI. Agarose gel electrophoresis results were abnormal, with 1 or more bands, in 25 of 29 SSA patients (86%), but in only 3 of 18 SSI patients (17%). Similar, but less striking, CSF abnormalities were seen in a minority of SLEA patients. Fifteen SSA patients (50%) had transient, mild‐to‐moderate CSF pleocytosis, while only 1 SSI patient and 2 SLEA patients had similar findings. Cytologic findings were abnormal in 18 SSA patients (60%); these included atypical mononuclear cells, lymphoblastoid cells, and plasma cells. The presence of immuno‐competent cells and evidence for the intrathecal synthesis of IgG within the CSF of SSA, but not SSI, patients provide diagnostic parameters which are indicative of active disease and which can be monitored serially during therapy.
Incidence of arthritis in urban finnish children: A prospective study
Authors: Kunnamo Ilkka , Kallio Pentti , Pelkonen Pirkko
Published: February 2007

The incidence of various types of arthritis in children was estimated by a prospective 1‐year study in the greater Helsinki area (population under 16 years of age: 148,362). Patients were sought from primary care physicians, and 71% of the patients studied were seen within 1 week of the onset of symptoms. All patients received followup care for at least 3 months; patients whose symptoms were prolonged received followup care for a minimum of 2 years. The incidence per 100,000 children under 16 years of age was as follows: 108.5 for all cases of arthritis, 6.7 for septic arthritis, 5.4 for enteropathic arthritis, 51.9 for transient synovitis of the hip, 18.9 for prolonged arthritis (duration >3 months), and 25.8 for acute transient arthritis. The incidence of juvenile rheumatoid arthritis was 19.6. Oligoarticular disease was prevalent (76%) among the juvenile rheumatoid arthritis patients.
Heterogeneity of proteoglycans extracted before and after collagenase treatment of human articular cartilage: I. Physical properties related to age
Authors: Van De Stadt Rob J. , Kuijer Roel , Van Kampen G. P. Jos , De Koning Margret H. M. T. , Van De Voorde‐Vissers Els , Van Der Korst Jan K.
Published: February 2007

Proteoglycans were isolated from young and mature human articular cartilage 4 different ways: by direct extraction with 4M guanidine hydrochloride (GuHCl); after digestion of the residue from this first extraction with collagenase, by extraction with 4M GuHCl; associatively with 0.5M GuHCl after digestion of the cartilage with collagenase; and dissociatively with 4M GuHCl after digestion of the cartilage with collagenase. The structural properties of these proteoglycans were compared. Proteoglycan aggregates and monomers isolated from second extractions and from young cartilage were of larger hydrodynamic size than proteoglycans isolated from first extractions and mature cartilage, respectively. The same applied to the chondroitin sulfate chain lengths of these proteoglycans. The proteoglycan fraction from second extractions of cartilage contained a larger proportion of monomers than the fraction from first extractions. Associative extraction of mature collagenase‐digested cartilage yielded mainly proteoglycan monomers, whereas an appreciable amount of proteoglycan aggregate was also liberated from young collagenase‐digested cartilage. Our results indicate that, because of their larger size, proteoglycans from second extractions of cartilage are more entrapped in the collagen network. These large proteoglycans can only be liberated from the matrix after extraction of the smaller proteoglycans, followed by digestion of the residue with collagenase. This indicates that proteoglycans overlap and entangle with the collagen and protect it from degradation by collagenase.
Anti‐SS‐A antibodies and fetal outcome in maternal systemic lupus erythematosus
Authors: Ramsey‐Goldman Rosalind , Hom David , Deng Jau‐Shyong , Ziegler Gayle Casterline , Kahl Leslie E. , Steen Virginia D. , Laporte Ronald E. , Medsger THOMAS A.
Published: February 2007

In 155 women with systemic lupus erythematosus, there were no significant differences in the rates of fertility or adverse fetal outcome between the 47 (30%) with serum anti‐SS‐A antibody and the 108 without anti‐SS‐A, except in the frequency of congenital heart block. This complication occurred in 6 of 96 pregnancies in women with anti‐SS‐A and was associated with high‐titer maternal antibody. The overall risk of a woman with lupus having an infant with congenital heart block was estimated to be 1:60, but the risk was considerably higher (1:20) if anti‐SS‐A antibody was present.
Rheumatoid nodulosis: Report of a case with evidence of intraosseous rheumatoid granuloma
Authors: Morales‐Piga Antonio , Elena‐Ibañez Angel , Zea‐Mendoza Antonio C. , Rocamora‐Ripoll Antonio , Beltrán‐Gutiérrez Juan
Published: February 2007

We describe a patient who had multiple subcutaneous rheumatoid nodules associated with episodes of acute intermittent arthritis and subchondral cystic lesions of the small bones of the hands and feet; this condition is termed “rheumatoid nodulosis.” The patient had a cystic lesion in communication with the joint cavity, rheumatoid granulomas, and evidence of a central zone of necrosis opening toward the joint space. His case is compared with 8 previously reported cases, and possible etiologies of the subchondral bone cyst formation in rheumatoid nodulosis are discussed.
Work disability among persons with musculoskeletal conditions
Authors: Yelin Edward H. , Henke Curtis J. , Epstein Wallace V.
Published: February 2007

We examined the question of what distinguishes persons with musculoskeletal disease who continue working after onset of illness from those who do not. We also investigated why persons with musculoskeletal disease have high rates of work disability relative to those with other chronic conditions of comparable activity limitation. Data regarding 3,100 persons with limitations in activities and chronic disease who were respondents to the 1978 Social Security Administration Survey of Disabled and Non‐Disabled Adults were used. Persons with musculoskeletal disease who stopped working had poorer overall health status and physical function, and different work attitudes and working conditions than did those who continued to work. Symptoms of the musculoskeletal condition were poor predictors of whether work disability would result. Persons with musculoskeletal conditions had high rates of work disability, relative to those with other chronic conditions, primarily because of their age, level of comorbidity, and the interaction of the physical limitations imposed by their illness and the requirements of their jobs. They had similar levels of commitment to work and a similar proclivity to seek alternative sources of income as did those with other chronic diseases.
Cytoskeletal binding of monoclonal anti‐dna antibodies derived from tonsillar lymphoid cells of a normal subject
Authors: Cairns EWA , Komar Ronald , Bell David A.
Published: February 2007

The ability of monoclonal IgM anti‐DNA auto‐antibodies derived from normal human lymphoid cells to bind to cellular constituents of human epithelial cells (HEp‐2) was examined by immunofluorescence. Hybridoma supernatants from 10 different clones were studied. Four of them gave a strong fibrillar cytoplasmic staining that resembled cytoskeletal staining, 1 showed strong nuclear staining only, 3 showed weak nucleolar staining only, and 2 showed no staining. The hybridoma supernatants that reacted with HEp‐2 cytoskeleton were either polyspecific for various nucleic acid antigens, such as single‐stranded DNA, DNA, poly(dA:dT), poly(dG)·poly(dC), RNA, and cardiolipin, or were restricted to cardiolipin. Cytoskeletal staining identical to the hybridoma supernatant staining was also seen with mouse monoclonal anti‐vimentin antibody B11.5.1. Inhibition of the cytoskeletal staining was accomplished in 3 of the 4 hybridoma supernatants by preabsorption of these hybridoma supernatants with cardiolipin and/or single‐stranded DNA, or by preincubation of the HEp‐2 cells with the mouse monoclonal anti‐vimentin antibody.
PREVALENCE OF COXSACKIE B VIRUS ANTIBODIES IN PATIENTS WITH JUVENILE DERMATOMYOSITIS
Authors: Christensen MARY L. , Pachman Lauren M. , Schneiderman Richard , Patel Devendrakumar C. , Friedman Jan M.
Published: February 2007

A number of viruses have been implicated as being the cause of various forms of myositis, including acute transient myositis, chronic polymyositis, and dermatomyositis. However, the cause of juvenile dermato‐myositis (JDM) has remained elusive. Our study of serum samples taken within 4 months of the onset of disease in 12 children with JDM showed that 83% had detectable titers of complement‐fixing (CF) antibody to 1 or more coxsackie B viral antigens. Detectable titers were found in only 25% of age‐, sex‐, and date‐matched control sera taken from 24 patients with juvenile rheumatoid arthritis (JRA), and in 25% of serum samples taken from 2,192 “normal” children who had been hospitalized because of viral syndromes. Titers of CF antibody to coxsackie B1, B2, and B4 were positive in 58%, 50%, and 58%, respectively, of the JDM patients. In matched JRA controls, the respective values were 8%, 13%, and 8%. There were no significant antiviral titers and no significant differences in the results of tests for 13 other viral CF antigens, hepatitis B surface antigen, and Mycoplasma pneumoniae CF antigen in the JDM patient sera compared with the JRA patient sera. When titers of neutralizing antibody were determined, 58%, 58%, and 67% of the JDM patients were positive for coxsackie B2, B4, and B5, respectively, whereas 16%, 26%, and 21%, respectively, of the JRA controls were positive for the 3 antigens. These data suggest that the host response to coxsackie B virus might be related to the pathophysiology of JDM.
A randomized, controlled trial of amitriptyline and naproxen in the treatment of patients with fibromyalgia
Authors: Goldenberg Don L. , Felson David T. , Dinerman Hal
Published: February 2007

Sixty‐two patients with fibromyalgia were randomly assigned to receive 25 mg of amitriptyline at night, 500 mg of naproxen twice daily, both amitriptyline and naproxen, or placebo in a 6‐week, double‐blind trial. Amitriptyline was associated with significant improvement in all outcome parameters, including patient and physician global assessments, patient pain, sleep difficulties, fatigue on awakening, and tender point score. Patients taking the combined naproxen—amitriptyline regimen experienced minor, but not significant, improvement in pain when compared with patients who took amitriptyline alone. Amitriptyline, or amitriptyline and naproxen, is an effective therapeutic regimen for patients with fibromyalgia.
In vitro synthesis of IgM rheumatoid factor in response to STAPHYLOCOCCUS AUREUS, by lymphocytes from healthy adults
Authors: Goldstein Rose , Karsh Jacob
Published: February 2007

Peripheral blood mononuclear cells from 20 healthy adults were tested in vitro for the production of IgM rheumatoid factor (RF) in response to Staphylococcus aureus Cowan I (SAC) or pokeweed mitogen. Fifteen of the 20 normal subjects produced ⩾4 ng/ml IgM‐RF (mean ± SD 46 ± 55 ng/ml) in response to SAC, compared with only 2 of 20 who produced ±4 ng/ml IgM‐RF (mean ± SD 2 ± 4 ng/ml) in response to pokeweed mitogen (P = 0.0001). Separation and reconstitution of autologous T and B cell‐enriched fractions, with and without prior T cell irradiation, provided evidence for a radiosensitive T helper/inducer cell involved in the IgM‐RF response to SAC in 70% of the normal subjects studied. SAC appears to be a potent stimulus of IgM‐RF production, with a cellular mechanism distinct from that of other in vitro systems.
Hypocomplementemia with low Cls‐Cl inhibitor complex in systemic lupus erythematosus
Authors: Lockshin M. D. , Qamar Tasneem , Redecha Patricia , Harpel P. C.
Published: February 2007

Ninety‐three serum and plasma samples from 45 patients with systemic lupus erythematosus were analyzed for the complex formed by Cls and its inhibitor, as well as for C3, C4, C4a desarginine, and staphylococcal protein A‐bound immune complexes. There were statistically significant correlations between Cls‐Cl inhibitor complex and CH50, between Cls‐Cl inhibitor complex and C4, and between Cls‐Cl inhibitor complex and C4a desarginine. Serial studies were performed on 24 patients over a period of 6 months. Seven of 21 patients with hypocomplementemia had persistently normal levels of Cls‐Cl inhibitor complex, 7 had transiently abnormal levels of Cls‐Cl inhibitor complex, and 7 had sustained abnormal levels of Cls‐Cl inhibitor complex. Two of 3 pregnant patients with normal levels of complement had abnormal levels of Cls‐Cl inhibitor complex. Staphylococcal protein A‐bound immune complexes demonstrated no correlation with any of the complement assays. Complement activation, as measured by Cls‐Cl inhibitor complex, is often a transient phenomenon in systemic lupus erythematosus patients with persistent hypocomplementemia.
Ankylosing spondylitis in families with two distinct B27 haplotypes: A selective association
Authors: Suarez‐Almazor Maria E. , Russell Anthony S. , Leclercq Sharon
Published: February 2007

Five families whose members had 2 distinct B27 haplotypes, and in which numerous members had ankylosing spondylitis (AS), were studied to see whether, in each family, both B27 haplotypes were associated with similar risks for the development of AS. In 4 of the 5 families, all family members with AS (4, 2, 3, and 2 individuals, respectively) shared the same B27 haplotype; however, 1 was homozygous for HLA‐B27 and carried both haplotypes. By statistical analysis, we showed that the B27 haplotype carried by the eldest member with AS in each family was more likely to be associated with disease. If additional genetic factors play a role in the development of AS, these preliminary findings suggest that they are probably located around the major histocompatibility complex.
Association between HLA and Sjögren's syndrome in Japanese patients
Authors: Moriuchi Junko , Ichikawa Yukinobu , Takaya Masatoshi , Shimizu Hiroaki , Uchiyama Mitsuaki , Sato Kaoru , Tsuji Kimiyoshi , Arimori Shigeru
Published: February 2007

Japanese patients with primary Sjögren's syndrome (SS), patients with SS and rheumatoid arthritis (SS‐RA), and patients with SS and connective tissue disease without RA (nonrheumatoid connective tissue disease [SS‐CTD]) were typed for HLA antigens. Patients with primary SS and those with SS‐RA had higher frequencies of DRw53 than did those who had SS‐CTD; however, the group with SS‐CTD showed a negative correlation with DRw52. These data indicate that Japanese and white patients with SS have different HLA specificities, and that genetic factors involved in the development of SS‐CTD might be different from those in primary SS and SS‐RA.
The natural history of fibromyalgia
Authors: Felson David T. , Goldenberg Don L.
Published: February 2007

The natural history of fibromyalgia was studied in 39 treated patients. All patients were surveyed by interviews conducted in 1983 (at an average of 1.3 years after diagnosis), in 1984, and again in 1985. Throughout the survey period, more than 60% of patients had moderate to severe continuing symptoms, and almost all took medications regularly to control symptoms. Younger patients (P = 0.02), those with less severe symptoms at the initial survey (P = 0.005), and those with isolated Raynaud's phenomenon (P = 0.04) were more likely to be doing well 2 years later, although symptom remission was usually transitory.
Long‐term followup of rheumatoid arthritis patients treated with total lymphoid irradiation
Authors: Tanay A. , Field E. H. , Hoppe R. T. , Strober S.
Published: February 2007

Total lymphoid irradiation was administered to 32 patients with intractable rheumatoid arthritis. Twenty‐four patients showed at least a 25% improvement in 3 of 4 disease activity parameters, which persisted during the followup period of up to 48 months. Eight of the 32 patients required adjunctive immunosuppressive drug therapy to maintain improvement. Four patients died after total lymphoid irradiation; the causes of death were acute myocardial infarction (1 patient), pulmonary embolism (1 patient), and rheumatoid lung disease complicated by respiratory infection (2 patients). After therapy, patients exhibited a prolonged reduction in the number and function of circulating T helper cells.
Cyclosporin A Treatment of Refractory Rheumatoid Arthritis
Authors: Weinblatt Michael E. , Coblyn Jonathan S. , Fraser Patricia A. , Anderson Ronald J. , Spragg Jocelyn , Trentham David E. , Austen K. Frank
Published: February 2007

Ten patients with rheumatoid arthritis were entered into a 24‐week pilot study of oral cyclosporin A at a starting dosage of 6 mg/kg/day, followed by a 12‐week washout period. Significant improvement in clinical parameters was observed at 12 weeks and 24 weeks (P < 0.02 versus baseline for joint pain and joint swelling indexes and patient and physician assessments; P < 0.04 versus baseline in the numbers of painful/tender joints and swollen joints). Adverse reactions were varied: renal impairment occurred in all patients and hypertension occurred in 7. All patients demonstrated an increase in defined disease activity at cessation of treatment and through the washout period. Cyclosporin A is clinically effective in the treatment of patients with refractory rheumatoid arthritis, but its value as an intervention therapy is limited by its toxicity.
Immunohistochemical characterization of synovial cells in arthritic mrl‐lpr/lpr mice
Authors: Tarkowski Andrej , Jonsson Roland , Holmdahl Rikard , Klareskog Lars
Published: February 2007

MRL‐lpr/lpr (MRL/l) mice spontaneously develop an autoimmune disease associated with arthritic manifestations. We used a recently developed mild demineralization procedure, followed by immunohistochemical staining of frozen sections, to investigate cell patterns in the hindlimbs of MRL/l mice at various stages of arthritic disease. Large numbers of Mac‐1 (Mas 034)–positive, macrophage‐like cells were seen both within the thickened synovial lining layer and in the deeper layers of the synovial tissue in all stages of arthritis. Ia‐expressing cells were scarce in the lining layer, but occurred in moderate numbers in the deeper layers of synovial tissue. Lymphocytes were totally absent in MRL/l joints in all stages of arthritis, as demonstrated by lack of staining with Ly‐1, Lyt‐2, GK 1,5, and antiimmunoglobulin antibodies. Our findings are discussed and related to other types of experimental arthritis and to rheumatoid arthritis in humans.
Evidence of the validity of the arthritis impact measurement scales
Authors: Potts Marilyn K. , Brandt Kenneth D.
Published: February 2007

The Arthritis Impact Measurement Scales (AIMS) were administered to 120 patients with rheumatoid arthritis. These patients also rated the importance of various aspects of their treatment. Our findings support the validity of the pain, anxiety, depression, dexterity, and physical activity subscales of the AIMS. The household activity subscale, however, may not be appropriate for use with men, and the activities of daily living subscale may be insensitive to mild impairment.
Nuclear ribonucleoprotein immune complexes in pericardial fluid of a patient with mixed connective tissue disease
Authors: Negoro Nobuo , Kanayama Yoshiharu , Yasuda Mitsutaka , Okamura Mikio , Amatsu Koji , Koda Shinichi , Takeda Tadanao , Inoue Takatoshi
Published: February 2007

We performed immunopathologic studies of the pericarditis present in a patient with mixed connective tissue disease. A large number of nuclear RNP (nRNP) immune complexes (ICs) were found in the pericardial fluid, but not in the serum. The pericardial small vessels had no deposits of IgG. These results suggest that locally formed nRNP ICs were closely associated with the pathogenesis of pericarditis in this patient.
A controlled study of concurrent therapy with a nonacetylated salicylate and naproxen in rheumatoid arthritis
Authors: Furst Daniel E. , Blocka Kenneth , Cassell Sidney , Harris E. Robert , Hirschberg Joel M. , Josephson Nathan , Lachenbruch Peter A. , Trimble R. Bruce , Paulus Harold E.
Published: February 2007

Previous studies of combinations of nonsteroidal drugs used in the treatment of rheumatoid arthritis (RA) have yielded conflicting results. We used standard methods to measure disease activity and high pressure liquid chromatography to measure plasma drug concentrations. We used doses of choline magnesium trisalicylate, adjusted to achieve therapeutic serum salicylate concentrations, and naproxen in a randomized, double‐blind, placebo‐controlled cross‐over study of full dose trisalicylate (CMT), full dose naproxen (N), full dose of both (CMT‐N), and half dose of both (cmt‐n) to examine their relative efficacy and toxicity in treating RA. CMT‐N was statistically superior to all other treatments in only 1 of 12 efficacy variables, but was equal to N and better than CMT or cmt‐n for 7 variables. There were minimal differences among treatments for the other 4 efficacy variables. The mean percentage difference for the efficacy variables between CMT‐N and N was 3%, between CMT‐N and CMT was 10.6%, and between CMT‐N and cmt‐n was 10.5%. Thirteen percent of patients manifested toxic reactions during the initial open dose‐adjustment salicylate run‐in phase. During the double‐blind phases of the study, CMT‐N was more toxic than N, CMT, or cmt‐n (7.5% versus 3.4%, 1.8%, and 3.7%, respectively). Tinnitus was more common when full‐dose CMT was used; N (N or CMT‐N) was associated with increased skin toxicity. Gastrointestinal complaints were equally common with all regimens. CMT‐N, although sometimes statistically superior to CMT, N, or cmt‐n, showed no clinically important additive or synergistic effect versus N or CMT alone.
Non‐hodgkin's lymphoma of the synovium simulating rheumatoid arthritis
Authors: Dorfman Howard D. , Siegel Howard L. , Perry Michael C. , Oxenhandler Ronald
Published: February 2007

Skeletal involvement in patients with non‐Hodgkin's lymphoma (NHL) is common, although direct involvement of the joints is unusual. We describe 2 adults who presented with features suggestive of a diagnosis of rheumatoid arthritis, but who were found to have diffuse NHL of the synovium. Results of a review of the literature, and assessment of the few similar cases in which NHL presented in the joint, suggest that the lymphoma may mimic either a monarticular or polyarticular synovitis, without lymphadenopathy or hepatosplenomegaly. Radiographic demonstration of associated bone destruction is the best evidence for non‐Hodgkin's lymphomatous arthropathy in patients with rheumatic symptoms.
Detection of antibodies to total histones and their subfractions in systemic lupus erythematosus patients and their asymptomatic relatives
Authors: Shoenfeld Y. , Segol G. , Segol O. , Neary B. , Klajman A. , Stollar B. D. , Isenberg D. A.
Published: February 2007

Sera drawn from 75 patients with systemic lupus erythematosus, 141 healthy relatives (from the families of 51 patients), and 115 healthy control subjects were examined, by enzyme‐linked immunosorbent assay, for IgG and IgM antibodies to total histones and their subfractions. Compared with the controls, statistically significant numbers of patients and their relatives had antihistone antibodies of both isotypes. Among the relatives, the sera from females, notably sisters of the patients, contained the highest levels of anti–total histone antibody. Anti‐H2A/H2B and H3 antibodies were most prevalent among the lupus patients, but many of the relatives had IgM anti‐H4 antibodies. These findings indicate that antihistone antibodies can serve as a genetic marker in patients with systemic lupus erythematosus.
Proteoglycan‐induced arthritis in balb/c mice
Authors: Glant Tibor T. , Mikecz Katalin , Arzoumanian Artin , Poole A. Robin
Published: February 2007

Immunization with chondroitinase ABC–digested fetal human cartilage proteoglycan and Freund's complete adjuvant induced polyarthritis and ankylosing spondylitis in female BALB/c mice. The initial external symptoms of the joint inflammation were swelling and redness. This was associated with edema of the synovium and periarticular tissues and gross proliferation of cells, which reached a peak during weeks 7–9 of the experiment. Mononuclear cell infiltration, with perivascular concentration and occlusion of small vessels, was common. Synovitis increased in severity, villous pannus developed, and erosions of bone, articular cartilage, and occasionally, growth plate were observed. The lumbar spine and the proximal intervertebral discs of the tail also exhibited inflammatory and degenerative changes. As the arthritis progressed, sometimes with acute inflammatory exacerbations, more joints became involved and, by the sixteenth to the twentieth weeks of the experiment, a progressive polyarthritis, with gross joint deformities and restricted function, developed in the majority of the limb joints. Clinical and morphologic features of the disease correlated well with radiologic analysis and with an increased deposition of 99mTc–methylene diphosphonate (determined by radionuclide imaging). The development of this arthritis was accompanied by the expression of cell‐mediated and humoral immunity to the immunizing antigen. However, this immunity was also observed, although it was generally less well developed, in mice that received the intact or digested proteoglycan without adjuvant. These mice did not usually develop arthritis. Control mice that received only adjuvant did not develop arthritis.
Arthritis care in older‐adult centers
Authors: Mazzuca Steven A. , Barger Gloria J. , Brandt Kenneth D.
Published: February 2007

In this study, we evaluated an inservice training program for public health nurses. The training program concerned arthritis screening and management of the disease in elderly subjects. Twenty‐nine nurses were assigned randomly to experimental (training) or control conditions. Evaluation data from 158 interviews with patients showed that screening for arthritis was done twice as frequently by nurses in the experimental group, compared with that done by nurses who were not in the experimental group (P < 0.01). Recommended management of arthritis was not correspondingly improved. Stronger inservice programs are discussed in light of the need to anticipate seasonal conflicts between arthritis care and preventive care for the elderly, to change habitual practice patterns, and to increase access to arthritis health professionals.
Nicardipine in the treatment of raynaud's phenomenon
Authors: Wigley Fredrick M. , Wise Robert A. , Malamet Raymond , Scott Thomas E.
Published: February 2007

A new calcium channel blocker, nicardipine, was studied for treatment of Raynaud's phenomenon in a double‐blind, placebo‐controlled, crossover trial during the winter months. Clinical response was assessed by a patient‐kept diary of symptoms and finger systolic pressure that was measured at room temperature and during cold challenge. In vivo platelet activation was determined by measuring plasma levels of the platelet‐specific proteins, beta‐thromboglobulin and platelet factor 4. When treatment with placebo was compared with treatment with nicardipine, no significant differences were found in the number of Raynaud's attacks per day, the severity of attacks, change in character in Raynaud's phenomenon, use of hands in winter months, patient assessment of medication or objective measurements of finger systolic pressure, and critical closing temperature. There was a reduction of plasma levels of beta‐thromboglobulin and platelet factor 4 in the overall study group while taking nicardipine compared with that during the placebo period (mean change 5.0 ± 2.4 ng/ml, P = 0.054, and 1.4 ± 0.6 ng/ml, P < 0.01, respectively). These results demonstrate that while nicardipine was not effective in reducing the episodes of Raynaud's phenomenon, it did inhibit in vivo platelet activation. These findings suggest that platelet activation is not the primary event in the pathogenesis of acute vasospasm in Raynaud's phenomenon, since reduction of platelet activation by the drug did not change the severity of vasospasm.
Giant cell arteritis, temporal arteritis, and polymyalgia rheumatica in a danish county
Authors: Boesen Per , Sørensen Søren Freiesleben
Published: February 2007

The annual incidence of giant cell arteritis (the term used in this study to encompass the syndromes of temporal arteritis and polymyalgia rheumatica, occurring either together or alone) was prospectively determined in a Danish county that had a population of approximately 200,000. In a single year, 46 new cases of giant cell arteritis were diagnosed, a number which corresponds to an incidence in the overall population of 21.5/105, and to an incidence of 76.6/105 for individuals age 50 years or older. These rates are higher than those previously reported in retrospective studies. The 3‐year followup of all patients showed no onset of other diseases that would require a revision of the original diagnosis. There was no deviation from the age‐ and sex‐specific malignancy rate or the mortality rate in the overall population. Women had an incidence rate 4 to 5 times higher than that seen in men. Symptoms, for the most part, were the same as those found in other studies; however, vision loss was not observed during the followup period. Point prevalence at the start of the study was 37.8/105, which is below the rates previously reported. This is probably because of failure on the part of participating physicians to record all cases.
Immunity to cartilage proteoglycans in balb/c mice with progressive polyarthritis and ankylosing spondylitis induced by injection of human cartilage proteoglycan
Authors: Mikecz Katalin , Glant Tibor T. , Poole A. Robin
Published: February 2007

Intraperitoneal injection of human fetal cartilage proteoglycan (depleted of chondroitin sulfate) in Freund's complete or incomplete adjuvant induces a chronic erosive polyarthritis and spondylitis in all female BALB/c mice. This occurrence is strain‐specific but not haplotype‐specific, and it is sex‐related. The development of the arthritis is associated with the natural presence of cellular immunity to the immunizing antigen and to chondroitinase ABC–treated mouse cartilage proteoglycan. In addition, relatively more antibody to the immunizing proteoglycan is elicited in arthritic mice, and antibodies are produced that cross‐react with native mouse proteoglycan. This combination of immune responses is not observed in mice that do not develop arthritis. Associated with the arthritis is the development of cytotoxicity to mouse chondrocytes and, in some animals, of rheumatoid factor, immune deposits in joint tissues and kidneys, and the production of autoantibodies to mouse type II collagen. These observations might be related to our earlier demonstration that immunity to human cartilage proteoglycan is observed in some patients with ankylosing spondylitis.
Antibodies to canine collagen types i and II in dogs with spontaneous cruciate ligament rupture and osteoarthritis
Authors: Niebauer Gert W. , Wolf Benjamin , Bashey Reza I. , Newton Charles D.
Published: February 2007

Antibodies to homologous collagens, types I and II, have been found in the sera and synovial fluids of dogs with spontaneous cruciate ligament rupture and osteoarthritis. Samples from 30 dogs with degenerative joint disease of the knee and from 15 healthy dogs were investigated by enzyme‐linked immunosorbent assay. Fifty‐three percent of dogs with joint disease showed significant levels of anti–type I collagen antibodies in their sera, and 56% had anti–type II reactivity. Ninety‐one percent of the dogs with joint disease exhibited antibody reactivity to type I collagen in their synovial fluid, and 88% showed reactivity to type II collagen. Correlation of these results with the clinical data indicated that the antibodies had been elicited by antigens derived from cruciate ligaments (type I collagen) and from altered joint cartilage (type II collagen). Immunologic reactivity in this form of canine osteoarthritis is a new concept, and it should be considered in our attempts to understand the pathogenesis of this disease.
Increase of dihydrofolate reductase in peripheral blood lymphocytes of rheumatoid arthritis patients treated with low‐dose oral methotrexate
Authors: Rodenhuis Sjoerd , Kremer Joel M. , Bertino Joseph R.
Published: February 2007

Because of a previously observed plateau of clinical response after long‐term methotrexate (MTX) therapy for rheumatoid arthritis (RA), we investigated whether such treatment might lead to acquired resistance to the drug. We studied the activity of dihydrofolate reductase (DHFR) (the target enzyme of MTX) in peripheral blood mononuclear cells of 11 RA patients who had been treated with MTX for a median of 43 months. The enzyme levels were markedly increased compared with levels found in the cells of 6 RA patients treated with other slow‐acting drugs. Quantitative dot‐blot analysis of DNA from 7 of these patients showed no evidence of DHFR gene amplification. No correlation was observed between increased levels of DHFR and either response to therapy or to the weekly MTX dosage. Phytohemagglutinin‐stimulated peripheral blood lymphocytes from 6 patients with increased levels of DHFR showed no evidence of MTX resistance in vitro. The increased DHFR levels may result from binding of MTX to the enzyme, which may block the normal degradation pathways; they do not appear to be a marker of impending drug resistance.
Identification of class ii HLA alloantibodies in placenta‐eluted gamma globulins used for treating rheumatoid arthritis
Authors: Moynier Marinette , Cosso Beatrice , Brochier J. , Clot J.
Published: February 2007

Placenta‐eluted gamma globulins (PEGG) have been recently and successfully used in the treatment of patients with rheumatoid arthritis. PEGG, eluted at acid pH from large pools of human placentas, contained 99% IgG material. Sephacryl S300 gel filtration revealed a main fraction (76%) of native IgG accompanied by 10% aggregates and 14% digested fragments (as identified by sodium dodecyl sulfate—polyacrylamide gel electrophoresis and immunoelectrophoresis with specific antisera). Previous in vitro data had suggested that alloantibodies to class II HLA antigens were present in this preparation. This study confirms that PEGG and F(ab')2 fragments were able to inhibit stimulating cells in mixed lymphocyte reactions. Additional findings showed that: (a) IgG from PEGG were cytotoxic for the non—T cell population; (b) IgG or F(ab')2 from PEGG bound only to class II HLA—bearing cells; (c) F(ab')2 from PEGG were able to block the complement‐mediated cytotoxicity of anti—HLA—DR and anti‐DQw1 alloantibodies. These data confirm the presence of class II HLA alloantibodies in PEGG. These antibodies may account for the clinical improvement reported in patients with rheumatoid arthritis. Our findings are similar to recent data showing that the injection of anti‐Ia antibodies in experimental animal models decreases the autoimmune process.
Anticardiolipin antibodies in patients with systemic lupus erythematosus
Authors: Sturfelt Gunnar , Nived Ola , Norberg Renée , Thorstensson Rigmor , Krook Katarina
Published: February 2007

We studied a group of 59 unselected patients with systemic lupus erythematosus (SLE); these patients were from a defined population who lived in southern Sweden. We found that serum concentrations of anticardiolipin antibodies were increased in 32 SLE patients (54.2%). No significant correlation between increased amounts of anticardiolipin antibodies and clinical symptoms, such as thrombocytopenia or thrombosis, was found. Serial serum samples from 28 patients (12 patients were from the epidemiologic cohort) were analyzed. Sixteen of these 28 patients (57.1%) had increased levels of anticardiolipin antibodies; in most cases, there was no variation in these values with regard to clinical disease flares or treatment. Increased concentrations of anticardiolipin were observed in 4 patients with cerebral infarction. However, very high concentrations of anticardiolipin antibodies were observed in several patients with inactive SLE who had no history of thrombosis or thrombocytopenia. Our results underscore the importance of studying unselected patient groups when correlating laboratory data with clinical manifestations of disease.
Receptor‐mediated binding of leukocyte elastase by chondrocytes
Authors: Bartholomew Jennifer S. , Lowther Denis A.
Published: February 2007

Studies on the effect of leukocyte elastase on the metabolism of chondrocytes in culture have demonstrated that these cells possess a specific cell surface receptor for leukocyte‐derived elastase. Purified elastase from rabbit and human leukocytes is capable of modulating the metabolism of the cell by causing a marked decrease in both proteoglycan and protein biosynthesis. Addition of 125I‐labeled elastase to chondrocytes maintained in suspension culture has shown that binding occurs, and that it is saturable and is inhibited by the addition of unlabeled enzyme. We ascertained that the active site of the enzyme was necessary for binding to the chondrocyte, since phenylmethylsulfonyl fluorideinactivated leukocyte elastase failed to bind. Pancreatic elastase had only a slight affinity for the receptor, whereas trypsin and bovine serum albumin failed to bind to any significant extent. Autoradiographic studies and the use of inhibitors of endocytosis, such as dansyl cadaverine, confirmed that endocytosis of elastase was the secondary event after cell binding.
Failure of tetracycline therapy in early lyme disease
Authors: Dattwyler Raymond J. , Halperin John J.
Published: February 2007

We describe the clinical courses of 5 patients with Lyme disease who developed significant late complications, despite receiving tetracycline early in the course of their illness. All 5 patients had been treated for erythema chronicum migrans with a course of tetracycline that met or exceeded current recommendations. The late manifestations of Lyme disease included arthritis, cranial nerve palsy, peripheral neuropathy, chronic fatigue, and changes in mental function. Our findings suggest that the use of tetracycline at a dosage of 250 mg, 4 times a day for 10 days, as a treatment for early Lyme disease should be reconsidered. To determine optimal therapy for early Lyme disease, a study that compares an increased dosage of tetracycline with alternative treatments is indicated.