bluuebunny/crossref_metadata_2025 huggingface dataset:
Arthritis‐associated changes in flow cytometric characteristics of cultured synovial fibroblasts
Authors: Eerola Erkki , Pulkki Kari , Pelliniemi Lauri J. , Granfors Kaisa , Vuorio Eero , Toivanen Auli
Published: February 2007

Synovial fibroblasts cultured from patients with rheumatoid or reactive arthritis and from controls were studied by flow cytometry, spectroscopy, and electron microscopy. Analysis of 29 cell lines revealed consistent differences between arthritic and normal fibroblasts. Cells cultured from inflamed synovial tissue exhibited higher autofluorescence than did control fibroblasts, and displayed exceptional light scatter properties in flow cytometry, indicating changes in cytoplasmic structures. Electron microscopic examination of the fibroblasts from arthritic synovial tissue revealed large numbers of round, swollen, laminated, mitochondrion‐like bodies, which were not observed in the control fibroblasts. The changes observed by flow cytometry (light scatter and autofluorescence) coincided with the presence of the mitochondrion‐like organelles. The strong autofluorescence observed in the arthritic fibroblasts resembled the fluorescence spectrum of mitochondrial flavoproteins. These data suggest that persistent metabolic and structural changes have occurred in the mitochondria of synovial fibroblasts and inflammatory synovial tissue. The usefulness of flow cytometry in identifying such cells is described.
Autoantibodies to mitochondria in systemic sclerosis. frequency and characterization using recombinant cloned autoantigen
Authors: Fregeau David R. , Leung Patrick S. C. , Coppel Ross L. , Mcneilage L. Jane , Medsger Thomas A. , Gershwin M. Eric
Published: February 2007

Mitochondrial autoantibodies, a hallmark of primary biliary cirrhosis (PBC), have been widely described for many years in patients with systemic sclerosis, and there have been several reports of the concurrence of systemic sclerosis and PBC. However, there is very little information with respect to the significance of these autoantibodies or any definitive evidence that the antigens involved represent the mitochondrial autoantigens (M2 complex) described in PBC. We have cloned and sequenced a rat complementary DNA which encodes for all the epitopes recognized by autoantibodies to the major, or 70‐kd, mitochondrial autoantigen in patients with PBC. Using this recombinant fused autoantigen, as well as by immunoblotting with human placental mitochondria, we tested for antimitochondrial antibody specificity in sera from 250 patients with systemic sclerosis. Nineteen sera (7.6%), including those from patients with CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias) and diffuse scleroderma, had reactivity with human placental mitochondria proteins by immunoblot testing. All 19 sera reacted with the M2 complex. All sera that reacted with the 70‐kd protein likewise reacted with the recombinant cloned autoantigen. The predominant autoantibody isotype to the 70‐kd protein was IgG3. Interestingly, the 70‐kd protein is 11% proline, an amino acid which is frequently preceded by hydrophobic amino acids.
Enhanced production of interleukin‐2 in patients with progressive systemic sclerosis. hyperactivity of cd4‐positive t cells?
Authors: Umehara Hisanori , Kumagai Shunichi , Ishida Hiroshi , Suginoshita Toshihiko , Maeda Michiyuki , Imura Hiroo
Published: February 2007

A significant enhancement of interleukin‐2 production was observed in phytohemagglutinin‐stimulated peripheral lymphocytes from patients with progressive systemic sclerosis (PSS). Their Leu‐3a:Leu‐2a ratio was also significantly higher than normal. Moreover, Leu‐3a+ cells freshly purified from PSS patients' blood produced much more interleukin‐2 than did cells from normal subjects. These results suggest that T cell hyperactivity, especially among Leu‐3a+ T cells, occurs in patients with PSS.
Encapsulation of indomethacin in liposomes provides protection against both gastric and intestinal ulceration when orally administered to rats
Authors: Soehngen Ellen C. , Godin‐Ostro Evelyn , Fielder Francis G. , Ginsberg Richard S. , Slusher Michael A. , Weiner Alan L.
Published: February 2007

Encapsulation of indomethacin into egg phospha‐tidylcholine (EPC) monophasic vesicles (MPV) or into stable plurilamellar vesicles (SPLV) before oral administration to rats substantially reduced or eliminated the gastric and intestinal ulceration normally associated with ingestion of this drug. Ulcers were assessed by the 4‐hour single‐dose gastric ulceration model and the 4‐ or 14‐day repeated‐dose intestinal ulceration model, using microscopic/planimetric quantitation. Oral dosages of up to 10 mg/kg of indomethacin in polyethylene glycol‐400 resulted in substantial gastric ulceration, but not when given in methylcellulose suspension or as EPCMPV. Severe intestinal ulcers resulted following oral administration of indomethacin in either vehicle at daily 3–4‐mg/kg doses, but did not result from EPCMPV formulations, whether dosed for 4 days or 14 days. Oral administration of pH‐sensitive indomethacin liposomes constructed from cholesterol hemisuccinate resulted in loss of the protective action. Indomethacin‐MPV showed both comparable bioactivity and comparable blood levels of the drug when contrasted with free drug in vehicles. Biodistribution studies demonstrated that when delivered from liposomes, drug and phospho‐lipid are rapidly cleared through the stomach but then are differentially absorbed. Empty EPCMPV given by mouth also offered some protection against ulcers induced by systemic (subcutaneous) introduction of indomethacin, although better protective action was noted when the drug was first liposome‐encapsulated and then given orally. The application of liposomes to the development of nonsteroidal antiinflammatory drugs that have minimal gastrointestinal side effects is discussed.
Some adverse reactions to allopurinol may be mediated by lymphocyte reactivity to oxypurinol
Authors: Emmerson B. T. , Hazelton R. A. , Frazer I. H.
Published: February 2007

Six of 9 patients with previously documented adverse reactions to allopurinol exhibited transformation of their peripheral blood lymphocytes when these were exposed in vitro to the allopurinol metabolite, oxypurinol. In 2 of these subjects, intradermal skin challenge was positive at 48 hours with either allopurinol or oxypurinol. The evidence presented suggests that some adverse reactions to allopurinol represent delayed‐type hypersensitivity to oxypurinol.
Augmented interleukin‐1 production and hla–dr expression in the synovium of rheumatoid arthritis patients
Authors: Miyasaka Nobuyuki , Sato Kazuto , Goto Makoto , Sasano Minoru , Natsuyama Motonobu , Inoue Kazuhiko , Nishioka Kusuki
Published: February 2007

Potent interleukin‐1 (IL‐1) activity was detected in culture supernatants from synovium, obtained by arthroscopy, from rheumatoid arthritis (RA) patients but not from non‐RA patients. Production of IL‐1 by RA synovium correlated well with findings of inflammation on arthroscopy and HLA–DR expression in immunohistochemical staining. Furthermore, there was a positive correlation between IL‐1 production from RA synovium and joint changes detected on roentgenograms. These findings strongly suggest that IL‐1 might play an important role in the joint destruction in RA.
Quantitative immunoassay of anti‐la antibodies using purified recombinant la antigen
Authors: T. Clair E. William S , Pisetsky David S. , Reich Charles F. , Chambers Jasemine C. , Keene Jack D.
Published: February 2007

A purified recombinant La fusion protein was tested in an enzyme‐linked immunosorbent assay to quantitate anti‐La responses. This protein contained the immunodominant region of the La molecule fused to β‐galactosidase. In solid‐phase assays, recombinant La protein was solubilized in urea and bound to polystyrene wells without loss of immunoreactivity. The recombinant‐based enzyme‐linked immunosorbent assay proved to be a sensitive method for the detection of anti‐La binding, and it accurately distinguished anti‐La precipitin positive sera from normal sera.
Ten‐year followup study of patients with yersinia arthritis
Authors: Leirisalo‐Repo Marjatta , Suoranta Hannu
Published: February 2007

Eighty‐five patients with acute Yersinia arthritis were seen in followup for a mean of 10 years. During that time, peripheral joint symptoms occurred frequently (51.8%), but these symptoms were mild (45.9%). Development of a new reactive arthritis (4.7%) or chronic arthritis (2.4%) was uncommon. One‐third of the patients experienced low back pain, and one‐third of the patients had radiologic evidence of sacroiliitis. The presence of sacroiliitis was more frequent in patients with low back pain (46.7%) than in those who did not have symptoms (21.2%). More patients with HLA–B27 had low back pain and sacroiliitis, but there was no association of this genetic factor with the residual symptoms in peripheral joints.
Pain management in rheumatoid arthritis patients
Authors: Parker Jerry C. , Frank Robert G. , Beck Niels C. , Smarr Karen L. , Buescher Keith L. , Phillips Les R. , Smith Elaine I. , Anderson Sharon K. , Walker Sara E.
Published: February 2007

To examine the effectiveness of a cognitive‐behavioral pain management program for patients with rheumatoid arthritis, three patient groups were studied: a cognitive‐behavioral group (CB), an attention‐placebo group, and a control group. The CB group received a comprehensive, 12‐month pain management program that taught coping strategies such as problem‐solving techniques, relaxation training, strategies for attention diversion, and training in family dynamics and communication. Dependent measures included pain, coping strategies, psychological status, functional status, and disease status. Data analysis at 12 months revealed benefits for the CB group in the area of enhanced coping strategies. Specifically, the CB subjects showed significantly greater use of coping strategies and significantly more confidence in their ability to manage pain. The findings are discussed in terms of the importance of enhanced self‐efficacy and personal control for patients with rheumatoid arthritis.
Reduced mandibular dimensions and asymmetry in juvenile rheumatoid arthritis
Authors: Stabrun Anne E. , Larheim Tore A. , Höyeraal Hans M. , Rösler Marek
Published: February 2007

The pathogenesis of reduced mandibular dimensions and asymmetry was studied in 103 patients with juvenile rheumatoid arthritis. Abnormalities of the temporomandibular joint were intimately related to mandibular growth disturbances. Unilateral joint abnormality resulted in jaw asymmetry and underdevelopment on the affected side. Duration of disease and of corticosteroid therapy, age at disease onset, and age when the data were recorded were correlated with the size of the mandible. Our findings did not support a hypothesis of cervical spine involvement as an etiologic factor of reduced mandibular size.
Increased levels of plasma anaphylatoxins in systemic lupus erythematosus predict flares of the disease and may elicit vascular injury in lupus cerebritis
Authors: Hopkins Patricia , Michael Belmont H. , Buyon Jill , Philips Mark , Weissmann Gerald , Abramson Steven B.
Published: February 2007

We measured levels of complement anaphylatoxin split products, C3a and C5a, in the circulation of patients with systemic lupus erythematosus (SLE). In 23 SLE patients who were followed serially, the mean C3a value was 179 ng/ml during stable disease and 550 ng/ml during a disease flare. In 10 patients, C3a levels predicted disease activity, with the C3a value rising from a mean of 183 ng/ml at a time of stable disease to a mean of 242 ng/ml 1–2 months prior to a clinical exacerbation of disease. The mean C3a level in 5 patients with acute dysfunction of the central nervous system (CNS) was 1,297 ng/ml, which is significantly higher than that observed in patients with active disease but without CNS involvement (P < 0.01). C5a levels were also significantly elevated in 4 patients with acute CNS disease. Pathologic specimens from 2 patients who died during an acute lupus flare revealed neutrophils occluding the cerebral and intestinal vessels. Fluorescein angiography in a patient with CNS lupus revealed vasoocclusive retinopathy. In 5 of 7 SLE patients who were pregnant, C3a levels were elevated, with a group mean value of 310 ng/ml. There was a negative correlation (r = – 0.59) between C3a and C3 levels in pregnant patients with SLE, and this finding is consistent with complement activation as the cause of decreasing C3 levels. We suggest that serial measurements of C3a can predict flares of disease in lupus patients and can demonstrate complement activation during pregnancy in women with SLE. In addition, release of C3a and C5a (mediators of inflammation) into the circulation may elicit vascular injury, particularly in patients with lupus cerebritis.
Activation of rat synovium by iron
Authors: Sousa Maria De , Dynesius‐Trentham Roselynn , Mota‐Garcia Fernando , Silva Manuel Teixeira Da , Trentham David E.
Published: February 2007

We observed a consistent sequence of activation changes in rat knee synovia following a single intravenous injection of sterile ferric citrate at a dosage sufficient to cause a transient saturation of transferrin. The initial alteration, appreciated 2 hours postinjection, consisted of an expansion in the lumen of synovial capillaries. At 8 hours, a thickening of the synovial lining and subsynovial tissue due to the hypervascularity and increased cellularity was noted, along with peaks in the mitotic activity of synovial cells (fourfold over baseline) and pinocytosis by endothelial cells. During the period of 8–24 hours, mature collagen appeared in the space between pericyte layers and between pericytes and endothelial cells, and 2–9‐fold increases in ferritin+, W3/13+, W3/25+, Ox8+, and Ox26+ mononuclear cells occurred. In contrast to the action on synovial fibroblasts, iron injection did not affect the mitotic activity of fibroblasts within the serosa of the small intestine. These findings demonstrate that, under experimental conditions, iron can readily induce changes in the synovium that are reminiscent of early events occurring in response to antigen.
Comparison of parotid and minor salivary gland biopsy specimens in the diagnosis of sjögren's syndrome
Authors: Wise Christopher M. , Agudelo Carlos A. , Semble Elliott L. , Stump Thomas E. , Woodruff Ralph D.
Published: February 2007

We conducted a prospective study comparing minor salivary gland and parotid gland biopsy specimens obtained simultaneously from 24 patients who were undergoing evaluation for primary Sjögren's syndrome (SS). Adequate tissue for study was obtained with all minor salivary gland biopsies and 19 of 24 parotid gland biopsies. Parotid inflammation was seen in 6 of 11 patients whose minor salivary gland biopsy results indicated SS, but in none of 8 patients who had normal findings on minor salivary gland biopsy. Patients with parotid inflammation were older and had a higher frequency of dry eyes and mouth, abnormal results on Schirmer's test, serious extraglandular involvement, and serologic abnormalities. We conclude that parotid gland biopsy adds very little to the minor salivary gland biopsy in the diagnosis of primary SS, but that parotid inflammatory changes may reflect disease duration and/or severity.
Immunologic dysfunction in scleroderma: evidence for increased mast cell releasability and hla–dr positivity in the dermis
Authors: Pearson Mark E. , Clark Huff J. , Giorno Ralph C. , Panicheewa Sucheelar , Claman Henry N. , Steigerwald James C.
Published: February 2007

To investigate the role of mast cells and cell‐mediated immunity in the pathogenesis of scleroderma, we studied wheal size after skin testing with compound 48/80, a liberator of mast cell histamine, and demonstrated increased mast cell releasability in skin that appeared normal, adjacent to involved skin. Immunofluorescent staining for HLA–DR showed dermal positivity in 12 of 13 involved‐ and 9 of 13 uninvolved‐skin biopsy specimens from scleroderma patients, compared with only 1 of 10 controls. By immunoperoxidase staining, most of the DR positivity was found in fibroblast‐like cells. These findings further support the notion of immunologic dysfunction in scleroderma.
Neonatal lupus risk to newborns of mothers with systemic lupus erythematosus
Authors: Lockshin Michael D. , Bonfa Eloisa , Elkon Keith , Druzin Maurice L.
Published: February 2007

We prospectively studied 91 infants born to women with systemic lupus erythematosus (SLE) or with SLE‐like disease. Thirty‐eight infants, including 3 sets of twins, were born to women who had anti‐Ro, anti‐La, or anti‐RNP antibodies. Four infants had definite neonatal lupus, and 4 had possible neonatal lupus. No prospectively studied infant had congenital heart block. The presence of neonatal lupus did not correlate with the titer of anti‐Ro antibodies. During the same time period, 2 additional babies with neonatal lupus and congenital heart block were born to mothers not previously known to have SLE. Taken together, these findings confirm the association of anti‐Ro antibody with neonatal lupus, but indicate that life‐threatening neonatal lupus is rare in children born to mothers who are known to have SLE, even when antibodies to Ro, La, or RNP are present. Prophylactic therapy is therefore not indicated for these women. An important proportion of mothers bearing children with neonatal lupus do not have recognized SLE and, currently, cannot be prospectively identified.
Soluble interleukin‐2 receptors in systemic lupus erythematosus
Authors: Wolf Robert E. , Brelsford William G.
Published: February 2007

We studied levels of soluble interleukin‐2 receptors (IL‐2R), which are released by activated lymphocytes, in 139 serum samples from 12 patients with systemic lupus erythematosus (SLE). Concentrations of soluble IL‐2R were significantly increased in SLE patients compared with controls (P < 0.001), and they were significantly higher in patients during active SLE defined by low C3 levels (P < 0.001), low C4 levels (P < 0.001), or proteinuria (P < 0.05) than during inactive SLE. Elevated levels of soluble IL‐2R correlated with hypocomplementemia in longitudinal studies (P < 0.001). Measurement of serum concentrations of soluble IL‐2R may provide a sensitive and specific method for monitoring disease activity and immune activation in patients with SLE.
Adjuvant‐induced polyarthritis. synovial cell activation prior to polyarthritis onset
Authors: López‐Bote Juan Pedro , Bernabeu Carmelo , Marquet Alberto , Fernández Jesús M. , Larraga Vicente
Published: February 2007

We studied synoviocytes obtained from rats that had been injected with Freund's complete adjuvant 12 days prior to killing. We found that several activation parameters were affected in these synoviocytes, namely, the concanavalin A protein‐binding pattern, the production of superoxide, and the appearance of the p77 polypeptide, which we have previously shown to be associated with the activation caused by the induction of polyarthritis. Our findings suggest that prior to the establishment of the inflammatory process, synoviocytes are in a state of activation, and may be a component of the molecular mechanism during the early stages of disease.
Synovial fluid lymphocytes in different subtypes of juvenile rheumatoid arthritis
Authors: Bergroth Ville , Konttinen Yrjö T. , Pelkonen Pirkko , Haapala Mervi , Haapasaari Jarkko , Nordström Dan , Kunnamo Ilkka , Friman Claes
Published: February 2007

We studied the subsets of synovial fluid (SF) lymphocytes and their activation states in 4 subtypes of juvenile rheumatoid arthritis. The expression of lymphocyte differentiation antigens and activation markers (Ia and Tac) appeared to be similar in these subgroups. Tac+ DNA‐synthesizing T blasts represented, at most, 5% of all SF mononuclear cells. This finding was in clear contrast to the high proportion of Ia‐positive SF mononuclear cells. There were no differences in Ia and Tac expression or DNA synthesis among the different juvenile rheumatoid arthritis subgroups. This finding suggests that the cell‐mediated immune response may represent secondary features of the disease that are involved as a final common pathogenetic pathway.
Apophyseal arthritis limits lumbar motion in patients with ankylosing spondylitis
Authors: Simkin Peter A. , Downey Daniel J. , Kilcoyne Ray F.
Published: February 2007

Ankylosing spondylitis patients who develop progressive spinal flexion may assume this posture to alleviate the pain of apophyseal arthritis. To examine this relationship, we scored injury to L4–L5 and L5–S1 apophyseal joints, as assessed by computed tomography, in 10 men with early ankylosing spondylitis. Both by the modified Schober test and by radiography of the lateral spine, impaired spinal motion correlated highly with evidence of apophyseal injury.
Deficient phytohemagglutinin‐induced interleukin‐2 activity in patients with inactive systemic lupus erythematosus is correctable by the addition of phorbol myristate acetate
Authors: Murakawa Yohko , Sakane Tsuyoshi
Published: February 2007

In systemic lupus erythematosus (SLE) patients, the production of interleukin‐2 (IL‐2) by blood T lymphocytes in response to stimulation with phytohemagglutinin (PHA) either alone or with phorbol myristate acetate (PMA) or ionomycin, a Ca2+ ionophore, was examined. Deficiency in PHA‐stimulated IL‐2 production by cells from SLE patients was repaired by the addition of PMA, but not ionomycin. PMA alone did not stimulate IL‐2 production but, in concert with PHA, induced IL‐2 synthesis. Moreover, PMA was effective in the repair of the deficiency of PHA‐induced IL‐2 production by both T4+ and T8+ subsets. Thus, for effective IL‐2 production, SLE T cells required signals either distinct from or in addition to those supplied by PHA.
Elevated soluble interleukin‐2 receptor levels in the sera and synovial fluids of patients with rheumatoid arthritis
Authors: Keystone E. C. , Snow K. M. , Bombardier C. , Chang Chi‐Hsing , Nelson D. L. , Rubin L. A.
Published: February 2007

In a previous study, we used an enzyme‐linked immunosorbent assay to measure soluble human interleukin‐2 receptors (IL‐2R), and found that when activated lymphocytes produce cell‐associated IL‐2R, they also release a soluble form of IL‐2R into culture supernatants in vitro. Soluble IL‐2R have also been detected circulating in vivo at low levels in the serum of healthy individuals, and at abnormal levels in a variety of diseases, particularly those where immune dysfunction is thought to play an important role. We therefore evaluated serum IL‐2R levels in 77 patients with rheumatoid arthritis (RA), and compared them with levels in 46 age‐matched healthy controls. Nineteen additional RA patients with concurrently obtained sera and synovial fluid (SF) samples were compared with 14 patients with osteoarthritis of the knee or hip. The serum IL‐2R levels were significantly elevated in RA patients, compared with the control groups (P < 0.0001). Serum IL‐2R levels in the RA patients did not correlate with disease activity as determined by a variety of clinical and laboratory parameters. RA SF IL‐2R levels were significantly higher than corresponding RA serum IL‐2R levels (P = 0.0001). No such difference was noted in the osteoarthritis group, where serum and SF IL‐2R levels were comparable with serum levels in healthy controls. These findings support the hypothesis that in vivo lymphocyte activation plays an important role in RA; moreover, soluble IL‐2R measurement in serum and SF may be a very useful way to identify patients at risk for, or manifesting, a chronic immune‐mediated inflammatory arthropathy.
Hybridoma lupus autoantibodies can bind major cytoskeletal filaments in the absence of DNA‐binding activity
Authors: Senécal Jean‐Luc , Rauch Joyce
Published: February 2007

A panel of 65 systemic lupus erythematosus (SLE) and 61 normal‐derived human hybridoma auto‐antibodies was studied for cytoskeletal reactivity, using an indirect immunofluorescence method. Reactivity with the cytoskeleton was expressed 3 times more frequently in the SLE‐derived antibody group and included intermediate filaments, microfilaments, microtubules, and centrioles. By immunoblot analysis, the antigenic specificity of intermediate filament—reactive SLE hybridoma antibodies was not restricted to vimentin, but included cytokeratins and desmin. The antibodies were also studied for their DNA‐binding, lupus anticoagulant, and rheumatoid factor activities. These autoantibody activities were expressed 3–5 times more frequently in the SLE‐derived group. The ability to bind DNA was not a prerequisite for reactivity with intermediate filament proteins. Our findings suggest that there are at least 2 subsets of cytoskeletal‐reactive hybridoma antibodies: those that recognize epitopes found only on cytoskeletal proteins, and those that recognize epitopes common to both DNA and certain cytoskeletal proteins. In addition, we hypothesize that there may be a third subset of antibodies that recognize a phosphate‐containing moiety (phospholipid or phosphoprotein) associated with cytoskeletal filaments.
Correlates of a clinical classification schema for the arthritis helplessness subscale
Authors: Stein Mitchell J. , Wallston Kenneth A. , Nicassio Perry M. , Castner Nancy M.
Published: February 2007

We examined the categorization of the helplessness subscale of the Arthritis Helplessness Index (AHI) into clinical ranges analogous to laboratory values, and the predictive validity of these cutoff scores over a 2‐year period. Data were obtained via questionnaires mailed every 6 months over 5 time periods to 368 patients who had been diagnosed as having rheumatoid arthritis. The results demonstrate that patients classified as low helpless were distinct from those classified as normal. In turn, those classified normal were distinct from high helpless patients on numerous measures of beliefs, affect, behavior, and symptom severity. Even after 2 years, the 5‐item helplessness subscale identified distinct clinical courses for these 3 groups.
Radial and spinal bone mineral density in a patient population
Authors: Mazess Richard B. , Barden Howard S. , Ettinger Mark
Published: February 2007

Density of the radius (by single‐photon absorptiometry) and the spine (by dual‐photon absorptiometry) was measured in 281 normal young women and in a large heterogenous group of 1,622 consecutive female patients. Both spinal and radial density were useful measurements when performed on patients with medical indications; spine and radius densities in these patients averaged 10–20% below those of age‐matched controls. However, patients younger than 60 years of age had deficits of spine density that were twice as large as those in the radius, and twice as many of these patients had spinal osteopenia, compared with those with radial osteopenia. After age 70, loss of density in the radius approximated that in the spine and the prevalence of osteopenia was similar at both sites. The poorer sensitivity of the radius measurement reflected the fact that it did not predict spine density. The standard error of the estimate was 0.12 gm/cm2 in normal subjects and 0.15 gm/cm2 in patients. At any given radial density, the spinal density of patients averaged 0.18 gm/cm2 (15–20%) below that in normal subjects. Predictions of spinal density from body weight were as accurate as predictions from radial density. Preferential spinal osteopenia occurring without radial osteopenia precluded radial densitometry as a screening method for individuals with osteoporosis before age 60. However, measurement of the radius was more effective than body weight for defining groups at risk, even though the radius did not reliably predict individual spine density. A radius shaft density < 0.55 gm/cm 2 occurring with a body weight < 55 kg was associated with a high prevalence of spinal osteopenia.
Peripheral lymphocyte depletion in gold sodium thiomalate—treated rheumatoid arthritis patients
Authors: Lundberg Max S. , Cannon Grant W. , Ward John R.
Published: February 2007

It has been reported that gold sodium thiomalate treatment of rheumatoid arthritis reduces the number of peripheral blood lymphocytes. In a prospective, double‐blind, randomized trial comparing gold sodium thiomalate, auranofin, and placebo in the treatment of rheumatoid arthritis, we investigated absolute lymphocyte counts. We found that peripheral lymphocyte counts decreased, but there was no correlation with clinical change in disease activity.
Bromocriptine suppresses postpartum exacerbation of collagen‐induced arthritis
Authors: Whyte A. , Williams R. O.
Published: February 2007

We administered bromocriptine (Parlodel) to arthritic mice immediately postpartum, and found that the drug suppressed the clinical exacerbation of joint involvement that was seen in untreated animals. Approximately 50% reduction in severity of disease was achieved with bromocriptine (P < 0.001). The effect may be due to suppression of the prolactin release that normally occurs postpartum.
Synovial microenvironment‐t cell interactions
Authors: Haynes Barton F. , Grover Betty J. , Whichard Leona P. , Hale Laura P. , Nunley James A. , Mccollum Donald E. , Singer Kay H.
Published: February 2007

Synovitis in rheumatoid arthritis is characterized by infiltration of the synovium by T and B lymphocytes and monocytes, as well as by the proliferation of synovial lining cells, fibroblasts, and endothelial cells. To study synovial cell‐T cell interactions in vitro, we established cultures of fibroblast‐like synovial cells, and used these cells in a synovial cell‐T cell binding assay. Using T cells at various stages of differentiation and activation, we found that human thymocytes and mitogen‐activated peripheral blood T cells bound to fibroblast‐like synovial cells, whereas fresh peripheral blood T cells did not. Moreover, activated T cells from inflammatory synovial tissue or from synovial fluid also bound to fibroblast‐like synovial cells cultured in vivo. Antibodies against certain epitopes of the T cell CD2 (35.1) and synovial cell lymphocyte function‐associated antigen‐3 (LFA‐3) (TS2/9) molecules inhibited synovial cell‐thymocyte binding. However, these same anti‐CD2 and anti‐LFA‐3 antibodies only partially inhibited synovial cell binding to activated normal peripheral blood T cells. Moreover, T cells from inflammatory synovium from rheumatoid arthritis and psoriatic arthritis patients also bound to synovial cells in vitro. These findings demonstrate that fibroblast‐like synovial cells are capable of binding to human T cells in vitro, and suggest that during the course of inflammatory synovitis, synovial fibroblast‐T cell interactions may occur in vivo.
Dqβ polymorphism and genetic susceptibility to felty's syndrome
Authors: Alex K. L. SO , Warner Catherine A. , Sansom David , Walport Mark J.
Published: February 2007

We used an oligonucleotide probe specific for a polymorphic sequence in the HLA‐DQβ gene to investigate the role of DQ polymorphism in genetic susceptibility to Felty's syndrome (FS) and rheumatoid arthritis (RA). The sequence of this gene was identified from a complementary DNA library derived from an RA patient's B lymphoblastoid cell line. With this probe, we studied the prevalence of the specific DQβ allele in DR4 positive FS patients, RA patients, and normal control subjects. Significantly more FS patients (17 of 25) showed hybridization with this oligonucleotide probe, compared with the number of DR4 positive non‐FS RA patients (7 of 23) and normal controls (7 of 21). The findings indicate that genes linked to the DQ region are important in determining susceptibility to FS.
Anti‐ige autoantibodies in systemic lupus erythematosus
Authors: Gruber Barry L. , Kaufman Lee D. , Marchese Mary J. , Roth William , Kaplan Allen P.
Published: February 2007

IgG and IgM autoantibodies directed against IgE were determined in 95 serum samples from 67 patients with systemic lupus erythematosus, by an enzyme‐linked immunosorbent assay. IgM anti‐IgE autoantibodies were found in 18 patients (27%) and IgG anti‐IgE autoantibodies were detected in 23 patients (34%). The specificity of the immunoassay was confirmed by the ability to inhibit binding with IgE myeloma, but not other immunoglobulin isotypes and the demonstration that the reactivity was directed to the Fc ε fragment of IgE. The IgG fraction of certain sera with anti‐IgE activity was capable of inducing histamine release from control basophils and cutaneous mast cells. Clinical associations with the presence of anti‐IgE activity were sought by retrospective chart analysis of 61 patients. Significant correlation was found with articular involvement, lymphadenopathy, and anti‐DNA antibodies (P < 0.05). Anti‐IgE autoantibodies are observed in a significant number of patients with systemic lupus erythematosus and may contribute to the pathogenesis of the vascular and articular lesions characteristic of this disease.
Distribution of chondroitin 4–sulfate and chondroitin 6–sulfate in human articular and growth cartilage
Authors: Mourão Paulo A. S.
Published: February 2007

The relative concentrations of chondroitin 4– and chondroitin 6–sulfate in different normal human cartilages are reported. Articular cartilages contained higher concentrations of chondroitin 6‐sulfate, whereas growth cartilages contained nearly equal amounts of chondroitin 4– and chondroitin 6–sulfate. Adult cartilages, in which the calcification process is already complete, contained only chondroitin 6–sulfate. The results suggest that chondroitin 6–sulfate is related to the integrity of the articular surfaces, whereas chondroitin 4–sulfate seems to be an important factor in the calcification process. The pathogenesis of the bone and cartilage alterations that occur in patients affected by heritable disorders of the sulfation of chondroitin sulfate are discussed in view of these findings.
Detection of tumor necrosis factor α but not tumor necrosis factor β in rheumatoid arthritis synovial fluid and serum
Authors: Saxne T. , Palladino M. A. , Heinegãrd D. , Talal N. , Wollheim F. A.
Published: February 2007

Synovial fluids from 6 of 12 patients with rheumatoid arthritis (RA) and from 3 of 11 patients with reactive arthritis contained measurable levels of tumor necrosis factor α (TNFα). Seven of 12 sera from RA patients contained TNFα, while only 1 of those from reactive arthritis patients was positive. Gamma‐inter‐feron was detected in the synovial fluids and sera of only the RA patients. Tumor necrosis factor β was not detected in any sera or synovial fluids. RA patients with detectable TNFα had higher erythrocyte sedimentation rates and synovial fluid leukocyte counts.
Studies of a common idiotype pr4 in autoimmune rheumatic disease
Authors: Williams W. , Zumla A. , Behrens R. , Locniskar M. , Voller A. , Mcadam K. P. W. J. , Isenberg D. A.
Published: February 2007

A new common idiotype, designated PR4, is described. This idiotype was originally identified on a human hybridoma‐derived monoclonal antibody from a patient with leprosy, which binds the major Mycobacterium leprae‐derived antigen, phenolic glycolipid‐1, poly(ADP)‐ribose, DNA, and poly(dT). The PR4 idiotype was found in patients with systemic lupus erythematosus (SLE) (70%), rheumatoid arthritis (40%), and Sjögren's syndrome (15%). It was not, however, found in the spouses of the SLE patients or (unlike other lupus idiotypes) in their healthy first‐degree relatives. Although no correlation between PR4 idiotype levels and disease activity in SLE was found, a subset of rheumatoid arthritis patients with high levels of the idiotype was identified.
Lupus retinopathy
Authors: Stafford‐Brady Frances J. , Urowitz Murray B. , Gladman Dafna D. , Easterbrook Michael
Published: February 2007

In a prospective study of 550 patients with systemic lupus erythematosus (SLE), 41 were found to have retinopathy. Lupus retinopathy in the majority of cases consisted of a microangiopathy, with an excellent prognosis for vision. Five patients developed other complications that resulted in loss of visual acuity. Lupus retinopathy was associated with active SLE in 88% of patients and with lupus cerebritis in 73% of cases. Retinopathy in SLE was a marker of poor prognosis for survival.
Mechanisms of joint damage in an experimental model of hemophilic arthritis
Authors: Madhok Rajan , Bennett David , Sturrock R. D. , Forbes Charles D.
Published: February 2007

Autologous whole blood was injected into the knee joints of rabbits 3 times each week for 12 weeks. The resulting destructive arthritis showed macroscopic and microscopic changes similar to those described in hemophilic arthritis in humans. Immunofluorescence studies indicated that a specific immune response is probably not involved in the pathogenesis of hemophilic arthritis. Detailed histopathologic examinations of knee joints in both the early and the late phase of arthritis revealed an obvious synovial and cartilage iron load, in the absence of inflammatory changes. The implications of these findings in the pathogenesis of destructive cartilage changes are discussed.
Partial C4A deficiency is associated with susceptibility to systemic lupus erythematosus in black americans
Authors: Wilson Wendell A. , Perez Myriam C. , Armatis Patricia E.
Published: February 2007

In a study of 59 black American patients with systemic lupus erythematosus (SLE), we found that partial C4A deficiency occurred twice as frequently as in 59 control subjects (32.3% versus 15.3%; P = 0.02). Complete C4A deficiency, however, occurred in only 1 patient and in no controls. Partial C4A deficiency is a risk factor for SLE in black, as well as in white, SLE populations studied to date. In contrast with white patients, complete C4A deficiency occurs relatively infrequently in black patients with SLE.
Reactive arthritis associated with shigella sonnei infection
Authors: Lauhio Anneli , Lähdevirta Juhani , Janes Rita , Kontiainen Sirkka , Repo Heikki
Published: February 2007

Several studies have failed to show an association between Shigella sonnei dysentery and reactive arthritis. We describe 3 patients who had reactive arthritis and a recent or concurrent S sonnei infection. To our knowledge, this is only the second study to suggest this association. We propose that S sonnei should be considered as a triggering agent for reactive arthritis.
Tuberculous rheumatism (poncet's disease) in a child
Authors: Southwood T. R. , Hancock E. J. , Petty R. E. , Malleson P. N. , Thiessen P. N.
Published: February 2007

A 2‐year‐old boy who had increasing difficulty walking and had large, warm, sterile knee and ankle effusions was found to have active vertebral tuberculosis and a large prevertebral abscess. Lymphocyte proliferation assays demonstrated increased purified protein derivative‐induced reactivity of synovial fluid lymphocytes compared with peripheral blood lymphocytes. The arthritis responded rapidly to antituberculous and antiinflammatory drugs. This patient's disease represented an example of tuberculous rheumatism (Poncet's disease).
A novel autoantibody causing a peripheral fluorescent antinuclear antibody pattern is specific for nuclear pore complexes
Authors: Dagenais André , Bibor‐Hardy Viviane , Senécal Jean‐Luc
Published: February 2007

We characterized serum from a patient with polymyositis, and found that it produced a peripheral (rim) fluorescent antinuclear antibody pattern on rat liver substrate. Indirect immunofluorescence analysis revealed a punctate pattern at the nuclear surface of PtK2, BHK‐21, and HEp‐2 cells. This pattern was still present after sequential extraction in situ with non‐ionic detergent, DNase, RNase, and high ionic strength buffer (2M NaCl). Immunogold electron microscopic localization was specific for nuclear pore complexes. By immunoblot analysis, the antigens were polypeptides of 200 kd and 130 kd that were enriched in the nuclear fraction.
Formal education level as a significant marker of clinical status in rheumatoid arthritis
Authors: Callahan Leigh F. , Pincus Theodore
Published: February 2007

Clinical status was assessed in 385 patients with rheumatoid arthritis, according to erythrocyte sedimentation rate, joint count, grip strength, walking time, and other quantitative measures. All measures indicated substantially poorer clinical status in patients who did not complete high school, compared with those who had completed high school. In general, the poorest results were seen in patients with only a grade school education. Progressively better results were seen in patients with some high school education, high school graduates, and patients with some college education. No differences in clinical status were seen among patients who had attended college, graduated from college, or had post‐graduate education. Although patients seen at the Veterans Administration Medical Center had lower levels of formal education than those seen at a university clinic and private practices, trends in clinical status according to formal education level were similar in all three clinical settings. Differences in clinical status according to formal education level are not explained by age, sex, duration of disease, clinical setting, or multiple comparisons. Formal education level may identify an important marker of clinical status in rheumatoid arthritis.
Serum levels of interleukin‐2 receptor and activity of rheumatic diseases characterized by immune system activation
Authors: Campen David H. , Horwitz David A. , Quismorio Francisco P. , Ehresmann Glenn R. , John Martin W.
Published: February 2007

Levels of interleukin‐2 receptors (IL‐2R), as measured by a double‐antibody “sandwich” enzyme‐linked immunosorbent assay technique, were markedly elevated in the serum of patients with systemic lupus erythematosus, rheumatoid arthritis, and bacterial endocarditis, but not in patients with acute gout. Serum levels of IL‐2R correlated strongly with clinical and laboratory indicators of disease activity in patients with lupus and in those with rheumatoid arthritis. This relationship was confirmed by sequential determinations in individual patients. Serum IL‐2R values correlated with disease activity better than did the Westergren erythrocyte sedimentation rate. Our findings indicate that serum levels of IL‐2R may serve as a reliable serologic indicator of disease activity in inflammatory diseases characterized by immune system activation.
Nonlinkage of the t cell receptor α, β, and γ genes to systemic lupus erythematosus in multiplex families
Authors: Wong David W. , Bentwich Zvi , Martinez‐Tarquino Carlos , Seidman J. G. , Duby Allan D. , Quertermous Thomas , Schur Peter H.
Published: February 2007

To test the possibility that T cell antigen receptor (TcR) genes are linked to the genes involved in the pathogenesis of systemic lupus erythematosus (SLE), genomic DNA restriction fragment length polymorphisms were studied, using the Southern blot technique, in 5 families with multiple members with SLE, 14 unrelated SLE patients, and 14 normal controls. Polymorphic patterns were detected with probes for all 3 TcR chains, but there was no significant difference in the distribution of the restriction fragment length polymorphism pattern among the patients, the relatives, and the controls. Furthermore, in the families with at least 2 individuals with the disease, each of the 3 TcR chain genes did not cosegregate with the disease. We conclude that TcRα, β, γ chain genes are not likely to be linked to genes related to SLE.
Postdysenteric reactive arthritis
Authors: Inman R. D. , Johnston M. E. A. , Hodge M. , Falk J. , Helewa A.
Published: February 2007

Following an outbreak of foodborne gastroenteritis caused by Salmonella typhimurium, questionnaires were sent to affected individuals and then to the family physicians of any who experienced extra‐enteric complications. Of 260 individuals infected with S typhimurium for whom adequate data were obtained, 19 patients developed joint disease (7.3%). All were men; the mean age ± SD was 39.3 ± 1.6 years. Among the 16 patients for whom this information was available, the interval from the onset of diarrhea to the onset of joint pain was <7 days in 7, 8–21 days in 2, and >21 days in 7. There was a significantly longer duration of diarrhea in those patients with joint disease (mean ± SEM 15.2 ± 2.6 days) than in those without complications (10.0 ± 1.1 days) (P < 0.01). The joint disease was monarticular in 3 patients and polyarticular in 16. The joints most commonly affected were the elbow (47%), wrist (47%), knee (42%), low back (32%), and shoulder (32%). Six of the 19 patients had at least 1 extraarticular feature: ocular (5 patients), mucosal (1 patient), urethral (2 patients), or cutaneous (1 patient). Of these 19 patients, 11 were located and agreed to HLA typing. Four were positive for HLA—B27, 6 were HLA—B7 positive, and 1 had HLA—Bw60. Of the 4 B27 positive patients, 3 were DR1 positive; of the 6 B7 positive patients, 5 were DR2 positive. A followup assessment 12.1 months after the acute infection revealed that of the 15 patients with arthritis (4 patients were lost to followup), 8 no longer had symptoms and 7 had persistent joint symptoms. Mucosal and urethral symptoms had resolved in all, and ocular symptoms had resolved in 90%. These findings highlight the interplay of microbe and major histocompatibility complex, a phenomenon that appears to be a precondition for the development of reactive arthritis.
Examination of subchondral bone architecture in experimental osteoarthritis by microscopic computed axial tomography
Authors: Layton Mark W. , Goldstein Steven A. , Goulet Robert W. , Feldkamp Lee A. , Kubinski David J. , Bole Giles G.
Published: February 2007

Subchondral bone changes have been proposed as an early event in the pathogenesis of osteoarthritis. In this study, microscopic computed axial tomography was used to evaluate the subchondral bone structure in femoral heads from a guinea pig model of osteoarthritis. Examination of trabecular bone within the femoral head showed a highly significant increase in bone fraction in the experimental animals. This was due to the development of trabeculae that were thicker and closer together. We conclude that trabecular remodeling may be an early event in this model of osteoarthritis.
Scleromyxedema myopathy: case report and review of the literature
Authors: Helfrich David J. , Walker E. R. , Martinez A. Julio , Medsger Thomas A.
Published: February 2007

We describe a patient who had scleromyxedema associated with proximal myopathy. The histopathologic and electron microscopic features are presented. In addition, we review the clinical and pathologic features of all 9 previously reported patients with documented scleromyxedema and myopathy. Proximal (pharyngeal) or distal dysphagia (7 of 7 patients), elevated creatine kinase (5 of 8), elevated aldolase (3 of 3), and electromyographically demonstrated myopathy (7 of 7) were usual features. Four patients had muscle biopsies that showed myofibril vacuolar changes, but inflammation was infrequent (2 cases). Our patient responded to oral prednisone and weekly intravenous methotrexate with improvement of the erythroderma, papular rash, and muscle strength.