bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel neuronal antigen identified by sera from patients with systemic lupus erythematosus
Authors: Hanly John G. , Rajaraman Selva , Behmann Sharon , Denburg Judah A.
Published: February 2007

Using human neuroblastoma cell lines (IMR‐6, NMB‐7, SK—c, SK—H) as sources, we characterized surface neuronal antigens as an initial step in determining the pathogenic role and clinical significance of neuronal antibodies in systemic lupus erythematosus (SLE) patients. SLE sera were screened for the presence of surface neuronal antibodies using a mixed hemadsorption assay. Thirty SLE sera were further tested by Western blotting and immunoprecipitation of lysed IMR‐6 cells. Western blotting revealed binding to predominantly intracellular antigens, none of which was restricted to neuroblastoma cells. In contrast, immunoprecipitation experiments demonstrated binding to a 97K antigen, which appeared to be of surface origin, by 3 SLE sera. This was not present on non‐neuronal cells and was not precipitated by sera from healthy or disease controls. This 97K antigen was also precipitated from the neuroblastoma cell line NMB‐7, but was not present on SK—c or SK—H cells. Precipitation was depleted by preabsorption with viable IMR‐6 and NMB‐7 cells, but not with non‐neuronal cells. Thus, some SLE sera recognize a 97K neuronal antigen on select neuroblastoma cells.
Acute nonlymphocytic leukemia following short‐term, intermittent, intravenous cyclophosphamide treatment of lupus nephritis
Authors: Gibbons Robert B. , Westerman Eric
Published: February 2007

Intermittent intravenous cyclophosphamide therapy has been shown to be effective in the management of lupus nephritis. There have been no reports of malignancies associated with such treatment regimens. We describe a patient who developed acute nonlymphocytic leukemia after receiving a total dose of 4 gm of cyclophosphamide over a 1‐year period.
Assessment of disease activity in essential cryoglobulinemia by serum levels of a basement membrane antigen, laminin
Authors: Gabrielli Armando , Marchegiani Gabriele , Rupoli Serena , Ansuini Giuseppina , Brocks Dietrich G. , Danieli Giovanni , Timpl Rupert
Published: February 2007

When compared with 40 normal controls, 46 patients with essential cryoglobulinemia had higher serum concentrations of a basement membrane antigen, laminin fragment P1 (LP1). Serum LP1 values were more pronounced in patients with visceral involvement, compared with those with skin vasculitis only. Asymptomatic patients or those with arthralgia usually had normal values. Increased disease activity was associated with a significant increase in LP1 (P < 0.01). For evaluation of disease activity, determination of serum LP1 was a more sensitive measure than any complement factor assay.
Prognosis in systemic lupus erythematosus
Authors: Reveille John D. , Bartolucci Alfred , Alarcón Graciela S.
Published: February 2007

To assess the impact of demographic and clinical factors on prognosis in patients with systemic lupus erythematosus (SLE), we examined survivorship by life‐table analysis in 389 patients. There were approximately equal numbers of Caucasian patients and American black patients in this study group. On both univariate and multivariate analyses, we found that both American black race and increasing age at SLE onset independently worsened the probability of survival. Of all the clinical factors we analyzed, thrombocytopenia emerged as the only independent risk factor for a worse prognosis in SLE. In all clinical and demographic groups considered, the leading cause of death was infection.
C‐MYC proto‐oncogene expression in peripheral blood mononuclear cells from patients with primary Sjögren's syndrome
Authors: Boumpas Dimitrios T. , Eleftheriades Elias G. , Molina Rudolpho , Barez Shirin , Atkinson Jane , Older Steven A. , Balow James E. , Tsokos George C.
Published: February 2007

We examined peripheral blood mononuclear cells (PBMC) from 16 patients with Sjögren's syndrome (SS) and 7 normal control subjects for the expression of the c‐myc proto‐oncogene. Patients with SS were found to have a significantly increased expression of c‐myc messenger RNA compared with normal individuals. No abnormal forms of c‐myc RNA were detected in the SS patients. DNA analysis did not show deletion, rearrangement, or amplification in the c‐myc proto‐oncogene. The methylation status of the c‐myc gene in patients with SS was found to be comparable with that of the control subjects. Nuclear run‐off assays showed increased transcription of the c‐myc gene in some patients but normal transcription in others, suggesting that posttranscriptional mechanisms are also involved in the increased c‐myc messenger RNA observed in these patients. Two patients with primary SS and B cell lymphomas were found to have normal c‐myc expression in their PBMC. These results demonstrate the presence of activated PBMC in patients with primary SS and delineate some of the mechanisms that are involved at the molecular level. We speculate that increased c‐myc expression may represent an early permissive event in the progression toward neoplasia in these patients.
Inhibition of osteoclastic bone resorption by mechanical stimulation in vitro
Authors: Klein‐Nulend Jenneke , Paul Veldhuijzen J. , Van Strien Michael E , Jong Marcel De , Burger Elisabeth H.
Published: February 2007

The influence of mechanical stimulation by intermittent compressive force (ICF) of physiologic magnitude on osteoclastic bone resorption was investigated in cultures of fetal mouse cartilaginous long bones. Exposure to ICF resulted in a significant decrease in mineral resorption, as indicated by the decreased release of 45Ca and a decreased number of osteoclasts in the diaphysis. Conditioned medium (CM) from ICF‐exposed periosteum‐free cultures (ICF‐CM), but not from control cultures (Co‐CM), inhibited mineral resorption in fresh bones cultured under control conditions. Co‐CM increased, but ICF‐CM decreased, the number of tartrate‐resistant acid phosphatase‐positive cells in 7‐day bone marrow cultures. Direct exposure of bone marrow cultures to ICF yielded the same results. Thus, osteoclastic bone resorption in cartilaginous long bones is inhibited by ICF in vitro. A soluble factor(s) acting on tartrate‐resistant acid phosphatase‐positive, osteoclast precursor‐like cells seems to play a role in this effect.
Hydrostatic and oncotic determinants of microvascular fluid balance in normal canine joints
Authors: Simkin Peter A. , Benedict Richard S.
Published: February 2007

Water moves between plasma (p) and synovial fluid (SF) in response to gradients in the balance of opposing hydrostatic pressures (HP) and oncotic pressures (OP). At the vascular site where proximal filtration ceases and distal reabsorption begins, all forces are theoretically in balance. At this point, the transitional microvascular pressure (TMP) may be estimated from the equation TMP = HPSF + OPp − OPSF. We measured these forces in the shoulders, wrists, and knees of 10 normal dogs, ages 2–10 years. The mean HPSF in the knee was lower than that in the shoulders and significantly lower than that in the wrist. Conversely, the OPSF in the wrist was significantly lower than that in the shoulder or the knee. These factors combined indicate that the microvascular bed in the normal knee has a remarkably low mean TMP (7.9 mm Hg). We also found a strong positive correlation between the age of each dog and the mean oncotic pressure of its SF.
Substance p and arthritis: analysis of plasma and synovial fluid levels
Authors: Wayne Marshall K. , Chiu Basil , Inman Robert D.
Published: February 2007

The uncadecapeptide substance P (SP), which is localized in peripheral and central terminals of afferent nerve fibers with polymodal nociceptors, has recently been implicated as having a neurogenic, inflammatory role in experimental arthritis. We used a radioimmunoassay to measure SP levels in plasma and synovial fluid samples from patients with rheumatoid arthritis (RA), osteoarthritis (OA), Reiter's syndrome (RS), and posttraumatic arthritis, as well as in plasma samples from 13 normal subjects. Plasma SP levels in RS patients exceeded levels in RA and OA patients, which in turn exceeded levels in posttrauma patients and in normal subjects. Synovial fluid SP levels exceeded respective plasma levels for all groups, except in RS patients, in whom the plasma level was not significantly different from that in synovial fluid. SP levels in synovial fluid of RA, OA, and RS patients did not differ significantly from each other, but the level in posttrauma patients was higher than in all other groups (P > 0.005). These studies demonstrate localized intraarticular SP release, and significant plasma/synovial fluid SP concentration gradients in several forms of arthritis.
Estrogen metabolism in the (New Zealand black × New Zealand white)F1 Murine model of systemic lupus erythematosus
Authors: Baer Alan N. , Green Floyd A.
Published: February 2007

Hepatic microsomal estrogen metabolism was analyzed in the (New Zealand black × New Zealand white)F1 ([NZB × NZW]F1) murine model of systemic lupus erythematosus. Both the estrogen 2‐hydroxylase activity (per mg microsomal protein) and the hepatic cytochrome P‐450 content were higher in premorbid (NZB × NZW)F1 mice, as compared with similarly aged nonautoimmune mice. However, these differences were not associated with alterations in the relative formation of the 2‐hydroxylated and the 16α‐hydroxylated metabolites. The development of overt nephritis was associated with a decrease in estrogen metabolic activity, but not with any alteration in the distribution of estrogen metabolites. Thus, estrogen metabolism was not altered in premorbid (NZB × NZW)F1 mice in a manner that would result in abnormal retention of hormonally active metabolites.
The american college of rheumatology 1990 criteria for the classification of fibromyalgia
Authors: Wolfe Frederick , Smythe Hugh A. , Yunus Muhammad B. , Bennett Robert M. , Bombardier Claire , Goldenberg Don L. , Tugwell Peter , Campbell Stephen M. , Abeles Micha , Clark Patricia , Fam Adel G. , Farber Stephen J. , Fiechtner Justus J. , Michael Franklin C. , Gatter Robert A. , Hamaty Daniel , Lessard James , Lichtbroun Alan S. , Masi Alfonse T. , Mccain Glenn A. , John Reynolds W. , Romano Thomas J. , Jon Russell I. , Sheon Robert P.
Published: February 2007

To develop criteria for the classification of fibromyalgia, we studied 558 consecutive patients: 293 patients with fibromyalgia and 265 control patients. Interviews and examinations were performed by trained, blinded assessors. Control patients for the group with primary fibromyalgia were matched for age and sex, and limited to patients with disorders that could be confused with primary fibromyalgia. Control patients for the group with secondary‐concomitant fibromyalgia were matched for age, sex, and concomitant rheumatic disorders. Widespread pain (axial plus upper and lower segment plus left‐ and right‐sided pain) was found in 97.6% of all patients with fibromyalgia and in 69.1% of all control patients. The combination of widespread pain and mild or greater tenderness in ⩾ 11 of 18 tender point sites yielded a sensitivity of 88.4% and a specificity of 81.1%. Primary fibromyalgia patients and secondary‐concomitant fibromyalgia patients did not differ statistically in any major study variable, and the criteria performed equally well in patients with and those without concomitant rheumatic conditions. The newly proposed criteria for the classification of fibromyalgia are 1) widespread painin combination with2) tenderness at 11 or more of the 18 specific tender point sites. No exclusions are made for the presence of concomitant radiographic or laboratory abnormalities. At the diagnostic or classification level, the distinction between primary fibromyalgia and secondary‐concomitant fibromyalgia (as defined in the text) is abandoned.
Osteoarthritis‐related changes in human articular cartilage
Authors: Vilamitjana‐Amedee J. , Harmand M.‐F.
Published: February 2007

We report the use of immunologic methods for detecting specific alterations in human osteoarthritic cartilage. Monoclonal antibodies with specificities for proteoglycans and link proteins have been used to define immunogenic sites in these molecules. We have identified 1 site in the protein core, 1 site in the link proteins, and another site that is common to both proteoglycan and link proteins, which are not modified in osteoarthritic cartilage. In addition, an antigenic determinant in link proteins that is altered in osteoarthritic cartilage has been identified. These results suggest that the structure of the ternary complex (hyaluronic acid binding region‐link proteins‐hyaluronic acid) could be altered in osteoarthritic cartilage. These modifications may be due to a genetic defect or to partial enzymatic degradation of these sites.
Metalloproteinases and cartilage proteoglycan depletion in chronic arthritis
Authors: Henderson B. , Pettipher E. R. , Murphy G.
Published: February 2007

Chronic monarticular arthritis can be induced in ovalbumin‐sensitized rabbits by intraarticular injection of ovalbumin (antigen‐induced arthritis) or in naive rabbits by injecting hyaluronic acid mixed with the polycation poly‐D‐lysine (polycation‐induced arthritis). Both models show some points of similarity, including joint swelling, the presence of inflammatory leukocytes and the inflammatory mediator prostaglandin E2, and the kinetics of cartilage proteoglycan loss. However, the assessment of the capacity of synovial lining and articular cartilage to synthesize and secrete neutral metalloproteinases reveals a difference between these models. We found that articular cartilage from the inflamed joints of rabbits with antigen‐induced arthritis did not synthesize neutral metalloproteinases, although the synovial lining did. In contrast, both the synovial lining and the articular cartilage from the inflamed joints of rabbits with polycation‐induced arthritis synthesized neutral metalloproteinases. These findings suggest that in inflammatory synovitis, different mechanisms can operate to produce damage to the matrix of articular cartilage.
The spectrum of atlanto axial facet joint involvement in rheumatoid arthritis
Authors: Halla James T. , Hardin Joe G.
Published: February 2007

Six hundred fifty outpatients with rheumatoid arthritis (RA) were evaluated and followed up during a 7‐year period. As part of their routine evaluation or because of neck‐shoulder girdle symptoms, 48% of the patients underwent routine cervical spine radiography. Sixty‐one RA patients (9% of the total population) had C1‐C2 involvement. Compared with the 589 patients with no evidence of C1‐C2 involvement, these 61 patients were significantly more likely to be younger, female, and seropositive, and they had significantly more nodules and erosions, as well as a longer disease duration. Based on radiographic evidence of C1‐C2 disease severity, 3 groups emerged. Group 1 (28 patients) had lateral mass collapse, group 2 (27 patients) had lateral facet joint sclerosis, erosion, or loss of joint space with no collapse, and group 3 (6 patients) had lateral subluxation with no bone or cartilage changes. Nine patients in group 1 had severe pain, and 25 had a nonreducible rotational tilt of the head. None of the patients in the other 2 groups had either of these signs or symptoms. Moreover, patients in group 1 were more likely to have other C1‐C2 or subaxial subluxations and were more likely to have myelopathy. C1‐C2 lateral facet joint involvement is common in RA, correlates with disease severity generally and specifically with that in the cervical spine, and, when severe, causes nonreducible rotational tilt of the patient's head.
Low‐dose methotrexate compared with auranofin in adult rheumatoid arthritis
Authors: Weinblatt Michael E. , Kaplan Herbert , Germain Bernard F. , Merriman Richard C. , Solomon Sheldon D. , Wall Bruce , Anderson Larry , Block Sidney , Irby Robert , Wolfe Frederick , Gall Eric , Torretti Dennis , Biundo Joseph , Small Ralph , Coblyn Jon , Polisson Richard
Published: February 2007

Weekly treatment with low‐dose oral methotrexate (MTX) was compared with daily auranofin (AUR) treatment in a 36‐week double‐blind, randomized, multicenter study of 281 patients with active, adult‐onset rheumatoid arthritis. Both treatment groups showed significant improvement by the usual measures of clinical efficacy. The response with MTX occurred earlier and was consistently greater than that with AUR. An intent‐to‐treat analysis showed significantly greater improvement (P < 0.01) with MTX for painful and swollen joint counts and physician and patient global assessments of disease activity. Adverse reactions were reported more frequently in the AUR group, and more AUR‐treated patients were withdrawn from the study because of toxicity. MTX was thus more effective and better tolerated than AUR in this study.
The role of stromelysin in the cartilage destruction that accompanies inflammatory arthritis
Authors: Hasty Karen A. , Reife Robert A. , Kang Andrew H. , Stuart John M.
Published: February 2007

Articular cartilage from arthritic joints of rats immunized with type II collagen is severely depleted of proteoglycans. Depletion begins within 48 hours after the onset of inflammation, prior to extensive pannus formation, and may represent a critical first step in cartilage destruction. We have immunolocalized stromelysin, an enzyme that is believed to play a major role in the pathologic degradation of proteoglycans, in the joints of rats with collagen‐induced arthritis. Immunoperoxidase staining of frozen tissue sections demonstrated the presence of stromelysin in both the synovium and chondrocytes. In contrast, collagenase was localized primarily to the pannus‐cartilage junction. Neither enzyme was detectable in joints from normal animals. To test the hypothesis that chondrocytes respond directly to inflammatory mediators by increasing the production of stromelysin, isolated chondrocytes were incubated with various concentrations of interleukin‐1. The culture media were also assayed for the presence of stromelysin by immunoreactivity on Western blots and by analysis of enzymatic activity on casein substrate gels. A 3‐fold increase in a doublet of proteins synthesized in response to 10 units/ml of interleukin‐1 was observed. These proteins also immunoreacted with the stromelysin antibody and degraded casein. Northern blotting results established that the increased levels of stromelysin were accompanied by increases in stromelysin‐specific messenger RNA levels. These results suggest that stromelysin is responsible for proteoglycan degradation in early inflammatory arthritis, and that chondrocytes may play a direct role in the earliest stages of the degradation of their own matrices.
Constitutive production of interleukin‐6 and immunologic features in cardiac myxomas
Authors: Jourdan Michel , Bataille Régis , Seguin Jacques , Zhang Xue Guang , Chaptal Paul André , Klein Bernard
Published: February 2007

The constitutive production of interleukin‐6 (IL‐6), a potent hepatocyte‐stimulating factor and B cell‐differentiating factor, was demonstrated in 3 patients with cardiac myxomas. Tumor cells from the only patient who presented with immunologic features produced 14–23‐fold higher levels of IL‐6 than those from the 2 patients who lacked such features. A significant serum IL‐6 level (56 pg/ml), greater than that observed in patients with active rheumatoid arthritis, was also observed only in this patient, with a subsequent return to an undetectable level after surgical removal of the tumor. This was associated with a regression of the immunologic features. This same patient was observed to have an IL‐6‐dependent, proliferative polyclonal plasmacytosis of the bone marrow. These observations demonstrate that an overproduction of IL‐6 by cardiac myxoma cells, in association with a systemic passage of this IL‐6, may be responsible for the immunologic features similar to those observed in true autoimmune diseases such as rheumatoid arthritis.
Pediatric onset of behcet's syndrome with myositis: case report and literature review illustrating unusual features
Authors: Lang Bianca A. , Laxer Ronald M. , Thorner Paul , Greenberg Mark , Silverman Earl D.
Published: February 2007

We report a case of Behcet's syndrome with myositis in a pediatric patient, emphasizing the importance of muscle involvement in the differential diagnosis of calf pain and swelling in Behcet's syndrome. A review of the English‐language literature from 1965 to the present suggests that the clinical picture of Behcet's syndrome in children differs from that in adults, in that there is a lower frequency of ocular disease, and unusual manifestations appear to be more common.
Characteristics of high‐titer igg antiphospholipid antibody in systemic lupus erythematosus patients with and without fetal death
Authors: Qamar Tasneem , Levy Roger A. , Sammaritano Lisa , Gharavi Azzudin E. , Lockshin Michael D.
Published: February 2007

Although high‐titer IgG antiphospholipid antibody (aPL) is a predictor of mid‐pregnancy fetal death in women with systemic lupus erythematosus (SLE), some SLE patients with high‐titer aPL carry pregnancies normally, and to term. To determine potential antibody differences between IgG aPL‐positive women with and without fetal death, we studied aPL isotype, subclass, anticoagulant activity, phospholipid specificity, and antibody avidity in selected sera from pregnant SLE patients with high‐titer IgG aPL. For controls, we selected sera from pregnant SLE patients who had negative results on tests for IgG aPL (with and without fetal loss). None of the specified antibody characteristics distinguished between the aPL‐positive patient groups, nor were other specificities defined in IgG aPL‐negative sera from women with fetal death. Although high‐titer aPL is a good predictor of fetal death, currently known characteristics, other than a high titer of aPL, do not identify which women will experience this complication.
Salivary gland echography in patients with sjögren's syndrome
Authors: Kawamura Hajime , Taniguchi Nobuyuki , Itoh Kouichi , Kano Shogo
Published: February 2007

Ultrasonographic examinations of salivary glands were performed on 24 patients with Sjögren's syndrome. On B‐mode echographic images, the submandibular glands of 21 of the patients (88%) showed a heterogeneous pattern, whereas all of the control subjects had homogeneous patterns. This distinction was further confirmed by the results of the analysis of the histogram patterns of echo intensity and echo frequency of the submandibular glands, which showed that the width of the echo level at 0% and 10% of the maximum normalized frequency was significantly greater in patients with Sjögren's syndrome than in the control subjects. Similar histographic findings were present in the parotid glands, although the heterogeneous ultrasonographic pattern was observed in only 8 of the 24 patients (33%). These results indicate that ultrasonography may be useful in the evaluation of salivary gland involvement in patients with Sjögren's syndrome.
Long‐term immunomodulatory effects of t lymphocyte depletion in patients with systemic sclerosis
Authors: Goronzy Jörg J. , Weyand Cornelia M.
Published: February 2007

We describe 2 patients with rapidly progressing systemic sclerosis that did not respond to conventional therapy, who were treated with a 5‐day regimen of T cell‐specific antilymphocyte globulin. One patient had deteriorating pulmonary involvement, and the second patient had developed disabling skin disease with multiple ulcers and gangrene. Both patients showed improvement concomitant with almost complete elimination of CD4+ and CD8+ T lymphocytes. Regeneration of peripheral T cells required 60–90 days and was followed by a long‐term inversion of the CD4:CD8 ratio. The persistent therapeutic effect in both patients correlated with the lack of CD4+ T cells and the predominance of CD8+ T cells. This suggests a crucial role of T cell immunity in the pathogenesis of systemic sclerosis. In vitro studies of regenerating T cells demonstrated that CD4+ helper/inducer cells were functionally competent. Alterations in the composition of the CD8+ population may explain the prolonged suppression of CD4+ T cells observed during the period of therapeutic benefit.
Effects of tumor necrosis factor α and β on resorption of human articular cartilage and production of plasminogen activator by human articular chondrocytes
Authors: Campbell Ian K. , Piccoli Diana S. , Roberts Michael J. , Muirden Kenneth D. , Hamilton John A.
Published: February 2007

We examined the effects of recombinant human tumor necrosis factor (TNF) on human articular cartilage and chondrocytes in culture. Both TNF α and TNFβ stimulated cartilage matrix breakdown during prolonged culture and elevated the levels of plasminogen activator (PA) activity in both the supernatants and cell layers of cultured chondrocytes. Characterization of the PA activities by immunochemistry and by zymography following gel electrophoresis indicated that human chondrocytes produce both urokinase‐type PA and tissuetype PA in response to TNF. The addition of both interleukin‐1 and TNFα or TNFβ to chondrocyte cultures demonstrated a synergism between these cytokines in the generation of PA activity in the culture supernatants and cell layers. Our results suggest that both activated lymphocytes and monocytes may contribute to the cartilage destruction of inflammatory arthritis through their stimulation of chondrocytes with TNFβ and TNFα, respectively. Since PA is the only neutral proteinase reported to be elevated in TNF‐stimulated chondrocyte cultures, it could have an important role in TNF‐mediated cartilage destruction.
The relationship of sulfoxidation status to efficacy and toxicity of penicillamine in the treatment of rheumatoid arthritis
Authors: Madhok R. , Zoma A. , Torley H. I. , Capell H. A. , Waring R. , Hunter J. A.
Published: February 2007

Penicillamine shows some structural similarities to carbocysteine. The ability to oxidize carbocysteine, i.e., the sulfoxidation status, shows a bimodal distribution in the general population. In this study, sulfoxidation status was determined in 50 of 60 rheumatoid arthritis patients receiving penicillamine. We found that poor sulfoxidation status, compared with good sulfoxidation status, was associated with a 3.9 times higher incidence of toxicity.
Sequence of i‐e genes from autoimmune new zealand white mice
Authors: Smith Lawrence R. , Theofilopoulos Argyrios N.
Published: February 2007

Autoimmune New Zealand white (NZW) mice contribute to (New Zealand black × New Zealand white)F1 mice 1 or more major histocompatibility complex‐linked genes that strongly correlate with susceptibility to murine lupus. The NZW class II major histocompatibility complex genes, I‐Eα and I‐Eβ, were cloned and sequenced and found to differ from normal B10.PL (H‐2u) mice by 3 amino acids in the first domain of the I‐Eβ subunit. Of these differences, the arginine at position 72 of NZW mice could be an important disease determinant since it lies in a predicted antigen‐binding cleft.
Secretion and binding of transforming growth factor β by scleroderma and normal dermal fibroblasts
Authors: Needleman Barbara White , Choi Jung , Burrows‐Mezu Alicia , Fontana Joseph A.
Published: February 2007

The production and binding of transforming growth factor β (TGF/β) were compared in dermal fibroblast lines derived from scleroderma patients and normal control donors. The mean ± SEM 24‐hour level of secretion of TGFβ by fibroblast lines derived from the involved skin of scleroderma patients was 30.8 ± 5.5 pmoles/106 cells, and it was 29.7 ± 5.8 pmoles/106 cells for fibroblast lines derived from the normal skin of the healthy donors. Thus, we found that the fibroblasts themselves produced TGFβ. TGFβ production was equivalent in fibroblast lines derived from clinically involved and uninvolved skin of scleroderma patients. The mean ± SEM number of TGFβ receptors per cell on scleroderma fibroblasts was 9,736 ± 1,375, with a mean ± SEM Kd of 25.2 ± 3.9 pM. This value was similar in control fibroblasts, at 12,431 ± 2,425 TGFβ receptors per cell, with a mean ± SEM Kd of 27.1 ± 5.2 pM.
Immunogenetic associations of scleroderma‐related antinuclear antibodies
Authors: Genth Ekkehard , Mierau Rudolf , Genetzky Petra , Von Mühlen Carlos A. , Kaufmann Sidonie , Wilmowsky Hubertus Von , Meurer Michael , Krieg Thomas , Pollmann Hans‐Joachim , Hartl Paul Walter
Published: February 2007

Patients selected for the presence of sclerodermarelated antibodies (anti‐DNA‐topoisomerase I [antitopo I; n = 43], anticentromere antibody [ACA; n = 63], or anti‐Pm‐Scl [n = 12]) were studied for class I and class II major histocompatibility complex antigens, as well as for Gm and Km allotypes. Anti‐topo I was associated with HLA‐DR5 (70% of patients versus 30.6% of controls; Pcorr = 0.0018, relative risk [RR] = 5.3). All patients with anti‐Pm‐Scl were positive for HLA‐DR3 (versus 23.5% of controls; Pcorr < 0.001); 6 of these patients were DR3/4 heterozygous (50% versus 3.5% of controls; Pcorr < 0.001, RR = 27.3). Patients with ACA were frequently positive for HLA‐DR1, DR4, or DRw8, with 73.7% demonstrating at least 1 of these alleles (versus 41.2% of controls; Pcorr = 0.0152, RR = 4.0). This group of ACA‐positive patients who had DR1, DR4, and/or DRw8 consisted mainly of a subgroup of patients with rheumatoid arthritis. We conclude that different class II major histocompatibility complex antigens influence the formation of anti‐topo I and anti‐Pm‐Scl. Important clinical differences between these patient groups and the immunogenetic heterogeneity support the notion of different antibody‐defined scleroderma subsets.
Human autoantibodies against the 70‐kd polypeptide of u1 small nuclear rnp are associated with hla‐dr4 among connective tissue disease patients
Authors: Hoffman Robert W. , Rettenmaier Lawrence J. , Takeda Yoshihiko , Hewett John E. , Pettersson Ingvar , Nyman Ulf , Luger Alan M. , Sharp Gordon C.
Published: February 2007

Serum samples from patients with connective tissue disease (CTD) were characterize using a recently developed enzyme‐linked immunosorbent assay for reactivity with individual specific polypeptides of U1 small nuclear ribonucleoproteins, including the U1‐70‐kd protein. The distribution of HLA antigens was compared in CTD patients with and in those without anti‐U1‐70‐kd autoantibodies and in normal controls. The frequencies of HLA‐DR4 and HLA‐DRw53 were increased among the anti‐U1‐70‐kd autoantibody positive CTD group compared with the frequencies in anti‐U1‐70‐kd autoantibody negative systemic lupus erythematosus patients and compared with normal controls. We conclude that the presence of autoantibodies reactive with the anti‐U1‐70‐kd protein antigen is associated with HLA‐DR4 and HLA‐DRw53.
The pill, parity, and rheumatoid arthritis
Authors: Spector Tim D. , Roman Eve , Silman Alan J.
Published: February 2007

We report on a case‐control study investigating the relationship of oral contraceptive pill (OCP) use and parity to the development of rheumatoid arthritis (RA). Women with RA were compared with 2 separate control groups, women with osteoarthritis (OA) and women randomly selected from a population‐based electoral register. Nulliparity was found to be a risk factor for the development of RA, with age‐adjusted odds ratios of 1.82 (95% confidence interval [CI] 1.09‐3.03) versus the OA control group and 1.83 (95% CI 1.03–3.06) versus the population control group. Use of OCPs before the age of 35 was negatively associated with RA (odds ratio 0.56, 95% CI 0.29–1.12 versus the OA control group; odds ratio 0.6, 95% CI 0.30–1.17 versus the population control group). Some evidence of a duration‐response effect was seen, although the numbers were small. The 2 variables were also multiplicative, with nulliparous non‐OCP users having a 4‐fold risk of RA compared with parous OCP users. These findings suggest that pregnancy and OCP use have a “protective effect” on the development of RA, although the mechanism remains unclear.
Radiographic followup of joints injected with triamcinolone hexacetonide for the management of childhood arthritis
Authors: Sparling Marcia , Malleson Peter , Wood Betty , Petty Ross
Published: February 2007

Evidence of deleterious effects following intraarticular injection of triamcinolone hexacetonide was sought through a review of radiographs of 145 joints of 55 children with chronic arthritis. Possible deleterious effects were noted in 16 joints of 11 patients. These effects included: small patella (2 joints), patellar osteochondritis dissecans (1 joint), periarticular calcification (9 joints), intraarticular tibial bony spur (1 joint), avascular necrosis of the distal radial epiphysis (2 joints), and avascular necrosis of the proximal femoral epiphysis (1 joint). Only the latter possible complication was symptomatic. Serial radiographs of 76 joints of 30 children showed mild progressive changes compatible with the underlying disease, except in the hip joint, where changes were more severe. The intraarticular injection of triamcinolone hexacetonide is a procedure that appears to be associated with an acceptably low frequency of radiologic abnormalities for many joints in children with chronic arthritis, but its effects on the hip joint remain uncertain.
In vitro identification of a subpopulation of fibroblasts that produces high levels of collagen in scleroderma patients
Authors: Needleman Barbara White , Ordonez Jose V. , Taramelli Donatella , Alms William , Gayer Karla , Choi Jung
Published: February 2007

A subpopulation of scleroderma dermal fibroblasts was identified by flow cytometric analysis. Between 15% and 25% of the cells within the scleroderma fibroblast lines had high levels of cytoplasmic granularity, as identified by side light scatter characteristics. Similar fibroblasts composed < 3% of the cells within the normal fibroblast lines, although greater numbers could be induced through exposure to soluble factors derived from activated mononuclear cells. The granular subpopulation of fibroblasts produced 2–3 times as much procollagen as did the other fibroblasts. These data support the hypothesis that fibrosis in scleroderma may result in part from the activity of an inherently high procollagen‐producing subset of normal fibroblasts that is expanded through exposure to immune cytokines.
The effect of marginal osteophytes on reduction of varus‐valgus instability in osteoarthritic knees
Authors: Pottenger Lawrence A. , Phillips Frank M. , Draganich Louis F.
Published: February 2007

The varus‐valgus stability of 20 knees with unicompartmental osteoarthritis was studied in vivo at the time of total knee replacement. Intact osteoarthritic knees had an average of 11.0° of varus‐valgus motion. Removal of osteophytes from the osteoarthritic compartment significantly increased the motion to 13.1° (P < 0.05), while subsequent removal of osteophytes from the nonosteoarthritic compartment further increased motion to 14.7° (P < 0.025). In primarily unicompartmental osteoarthritis, marginal osteophytes appear to stabilize osteoarthritic knees, but can cause fixed deformity.
Bullous Photosensitivity To Naproxen: “Pseudoporphyria”
Authors: Suarez Sylvia M. , Cohen Philip R. , Deleo Vincent A.
Published: February 2007

Pseudoporphyria is a photo‐induced cutaneous bullous disease characterized by distinct clinical, histologic, and most recently, immunofluorescent features. By definition, results of porphyrin studies are normal in this disease. We describe here a woman with naproxen‐induced pseudoporphyria, and we review previously reported cases of pseudoporphyria. The increasing frequency of pseudoporphyria is a result of the current popularity of nonsteroidal antiinflammatory drugs. Physicians need to be aware of this reversible skin disorder. Pseudoporphyria must be considered and an appropriate evaluation must be done when an individual who is taking nonsteroidal antiinflammatory drugs develops bullae and increased fragility of exposed skin.
Exogenous sex hormones and the risk of rheumatoid arthritis
Authors: Hernandez‐Avila Mauricio , Liang Matthew H. , Willett Walter C. , Stampfer Meir J. , Colditz Graham A. , Rosner Bernard , Chang Roland W. , Hennekens Charles H. , Speizer Frank E.
Published: February 2007

The use of exogenous sex hormones in relaiton to the risk of rheumatoid arthiritis (RA) was examined in a cohort of married nurses 30–55 years of age followed since 1976 in the Nurses' Health Study. Baseline information on the use of oral contraceptives, replacement estrogens, and other potential risk factors was obtianed in 1976 and updated every 2 years. During 8 years of followup, 217 incident cases of polyarthritis were ascertained (115 RA and 102 undifferentiated polyarthritis). When compared with women who had never used oral contraceptives, the age‐adjusted relative risk was 1.0 (95% confidence interval [CI] 0.7–1.3) for past users; however, too few women were currently using oral contraceptives for a reliable estimate of its effect. Among postmenopausal women, 123 cases of RA were reported. Compared with postmenopausal women who never used replacement estrogens, current users had an age‐adjusted relative risk of 1.3 (95% CI 0.9–2.0), past users had an age‐adjusted relative risk of 0.7 (95% CI 0.5–1.2), and ever users had a relative risk of 1.0 (95% CI 0.7–1.4). These data do not show a protective effect of past use of oral contraceptives or replacement estrogens for RA; however, a modest protective effect of current oral contraceptive use cannot be excluded.
Histologic and electron microscopic characterization of the antiperinuclear factor antigen
Authors: Vivino Frederick B. , Maul Gerd G.
Published: February 2007

The presence of the antiperinuclear factor, an autoantibody that recognizes cytoplasmic antigens, was detected in sera from patients with rheumatoid arthritis (59%), seronegative rheumatoid arthritis (36%), systemic lupus erythematosus (46%), systemic sclerosis (26%), and in nonautoimmune controls (10%). The antigenic perinuclear granules were found in the stratum intermedium layer of the buccal mucosa. Granules exhibited histologic features of nucleoproteins, stained for ribonucleoprotein, and showed the ultrastructural characteristics of aggregated rough endoplasmic reticulum. The antiperinuclear factor may recognize a common autoantigen in connective tissue disease.
Contribution of renal biopsy data in predicting outcome in lupus nephritis: analysis of 116 patients
Authors: Nossent Hans C. , Henzen‐Logmans Sonja C. , Vroom Thea M. , Berden Jo H. M. , Swaak Tom J. G.
Published: February 2007

We reassessed renal biopsy specimens from 116 patients with systemic lupus erythematosus and clinical manifestations of lupus nephritis to determine the contributions of the World Health Organization classification system, the activity and chronicity indexes of the National Institutes of Health scoring system, and various clinical parameters at the time of biopsy to predicting disease outcome. Multivariate analysis showed that only a chronicity index >3 was predictive for decreased renal survival, while age >31 years at biopsy and a chronicity index >3 were associated with decreased patient survival. Clinical tests of renal function were not reliable in discriminating between active lesions and chronic renal damage.
Hepatitis with bridging fibrosis and reversible hepatic insufficiency in a woman with rheumatoid arthritis taking methotrexate
Authors: Kujala G. A. , Shamma'A J. M. , Chang W. L. , Brick J. E.
Published: February 2007

A patient with seropositive rheumatoid arthritis developed ascites while taking weekly doses of methotrexate (MTX). Her serum transaminase and albumin levels were normal. A liver biopsy revealed chronic hepatitis with bridging fibrosis and piecemeal necrosis. Upon discontinuation of MTX, her ascites resolved, and her arthritis became more active. This is the third report of reversible hepatic decompensation associated with prolonged MTX therapy in patients with rheumatoid arthritis.
Evaluation of the 1987 revised criteria for rheumatoid arthritis in a cohort of newly diagnosed female patients
Authors: Dugowson Carin E. , Nelson J. Lee , Koepsell Thomas D.
Published: February 2007

The revised criteria for the diagnosis of rheumatoid arthritis (RA) were presented in 1987. We tested these criteria on 135 women from a population‐based study of patients with newly diagnosed RA. None of the 19 women with probable RA and 100 of the 116 women with definite RA met the 1987 criteria. The 1987 criteria appear to be less sensitive or more specific than the criteria formulated in 1956.
Rheumatologic manifestations of human parvovirus B19 infection in adults. Initial Two‐Year Clinical Experience
Authors: Naides Stanley J. , Scharosch Laura L. , Foto Frank , Howard Elizabeth J.
Published: February 2007

During 1987 and 1988, we identified 9 adults at the Medical and Rheumatology Services of the University of Iowa Hospitals and Clinics who had a clinical diagnosis of fifth disease; 8 of the 9 had symptoms of joint involvement. Another 12 adults with serologic positivity for anti‐parvovirus B19 IgM antibody presented with polyarthralgia/polyarthritis. Patients were usually found to be seronegative for rheumatoid factor, and none developed nodules or erosive disease. Many patients with chronic disease met criteria for a diagnosis of rheumatoid arthritis. A diagnosis of parvovirus B19 infection should be considered during the initial visit of patients with polyarthralgia/polyarthritis.
Immunologic parameters of response in patients with rheumatoid arthritis treated with cyclosporin a
Authors: Yocum David E. , Wilder Ronald L. , Dougherty Suanne , Klippel John H. , Pillemer Stanley , Wahl Sharon
Published: February 2007

Thirty‐one patients with seropositive rheumatoid arthritis treated with cyclosporin A (CsA) were evaluated for immune function prior to, during, and after 1 year of therapy. Patients whose pretreatment peripheral blood mononuclear cells were hypoproliferative in vitro to soluble recall antigens responded better clinically to CsA treatment than did the other patients. During therapy, proliferative responses became normal and remained so until 1–2 months after CsA was discontinued. At that time, the lymphocyte proliferation defect reappeared. In addition, patients who responded clinically to CsA had a higher percentage of Leu‐7+ natural killer cells in their peripheral blood prior to therapy. All patients exhibited greater frequencies of cells that expressed interleukin‐2 receptors, which decreased with CsA treatment. The clinical response to CsA appears to be associated with distinct immunologic parameters in rheumatoid arthritis.
A clue from a self‐report questionnaire to distinguish rheumatoid arthritis from noninflammatory diffuse musculoskeletal pain
Authors: Callahan Leigh F. , Pincus Theodore
Published: February 2007

A clue to distinguishing rheumatoid arthritis (RA) from noninflammatory diffuse musculoskeletal pain is described on the basis of 2 self‐report questionnaire scales, one to assess difficulty in activities of daily living (D‐ADL) and a pain visual analog scale (P‐VAS). Patients with RA have significantly higher scores on the D‐ADL scale compared with the P‐VAS scale, while patients with noninflammatory diffuse musculoskeletal pain show the reciprocal pattern. Therefore, the ratio of the P‐VAS:D‐ADL scores differed significantly in the 2 groups. Ratios of <3 were seen in 67% of RA patients versus 28% of patients with noninflammatory diffuse musculoskeletal pain, while ratios >5 were seen in 27% of patients with noninflammatory diffuse musculoskeletal pain, but not in any patients with RA. This simple ratio is clearly not a diagnostic test, but provides an initial approach to diagnosis in rheumatic diseases using a self‐report questionnaire.
Lysis of fibrillar collagen by neutrophils in synovial fluid. A Role for Surface‐Bound Immunoglobulins
Authors: Chatham W. Winn , Heck Louis W. , Blackburn Warren D.
Published: February 2007

Synovial fluids (SF) contain inhibitors capable of neutralizing the activity of proteases secreted by inflammatory cells and fibroblasts. To further define a potential role for SF polymorphonuclear neutrophils (PMN) in mediating joint destruction, peripheral blood PMN were suspended in SF and incubated with reconstituted collagen fibrils. Incubation of PMN‐SF mixtures with collagen fibrils precoated with monomeric IgG resulted in significant lysis of the underlying fibrils relative to that seen with uncoated fibrils. Augmented fibril lysis by PMN‐SF mixtures in which the PMN were activated with fluid‐phase ligands such as phorbol myristate acetate or heat‐aggregated IgG was not seen. Lysis of IgG‐coated fibrils by PMN‐SF was inhibited in the presence of EDTA or sodium azide. PMN‐mediated resorption of fibrillar collagen occurred despite the presence of protease inhibitors in the SF at a concentration capable of neutralizing human neutrophil collagenase. These results suggest that the focal release and activation of human neutrophil collagenase during PMN stimulation by tissue‐bound immunoglobulins may mediate the resorption of joint tissue collagens in rheumatoid arthritis, even in the presence of protease inhibitors.
In vitro secretion of human IgM rheumatoid factor. Evidence for Distinct Rheumatoid Factor Populations in Health and Disease
Authors: Dalal Niloofer , Roman Sheryl , Levinson Arnold I.
Published: February 2007

The production of antibodies that react with the Fc fragment of IgG, i.e., rheumatoid factors (RF), is now regarded as a normal host immune response. It is not clear, however, if such putative physiologic RF are different from their counterparts which characterize pathologic states like rheumatoid arthritis (RA). Using Staphylococcus aureus Cowan I as an in vitro stimulant of RF production, we now report that the IgM‐RF secreted by blood mononuclear cells obtained from healthy newborn infants and healthy adults can be distinguished not only from classic monoclonal RF and polyclonal RA serum RF, but also from the RF secreted by blood mononuclear cells obtained from RA patients. Whereas the Fc‐binding activity of all RF secreted in vitro was easily inhibited by aggregated human IgG, only the RF produced by the normal umbilical cord cells and the normal adult cells were inhibited by monomeric Fc(IgG). The normal RF were also selectively inhibited by monomeric rabbit and guinea pig Fc(IgG). The RF secreted by umbilical cord blood cells utilized λ and λ light chains, with a disproportionate use of λ light chains relative to the total IgM secreted. Together, these data provide evidence for distinct subsets of RF in health and in disease.
Soluble interleukin‐2 receptors in children with kawasaki syndrome
Authors: Barron Karyl S. , Montalvo Juan F. , Joseph Aaron K. , Hilario Maria O. , Saadeh Constantine , Giannini Edward H. , Orson Frank M.
Published: February 2007

We studied levels of soluble interleukin‐2 receptors (IL‐2R) in serial serum samples obtained from 93 patients with Kawasaki syndrome, using a double‐antibody “sandwich” enzyme‐linked immunosorbent assay technique. Concentrations of soluble IL‐2R were significantly increased in Kawasaki syndrome patients in the first 4 weeks of illness when compared with either healthy adult or pediatric controls (P < 0.02), and in the first 2 weeks of illness when compared with a group of children with measles (P < 0.0001). Furthermore, in the second week of illness, levels of soluble IL‐2R were significantly greater in children who subsequently developed coronary artery aneurysms than in patients with normal appearing coronary arteries. Serum concentration of soluble IL‐2R is a useful marker for detecting early Kawasaki syndrome and identifies those patients who are at greater risk of developing coronary artery aneurysms.