bluuebunny/crossref_metadata_2025 huggingface dataset:
A recombinant autoantigen derived from the human (u1) small nuclear rnp‐specific 68‐kd protein
Authors: Netter Hans Jürgen , Guldner Hans Herbert , Szostecki Carin , Lakomek Heinz‐Jürgen , Will Hans
Published: February 2007

A human liver complementary DNA expression library was screened using sera from patients with high titers of autoantibodies, to search for clones expressing major autoantigens that are relevant in connective tissue diseases. One of the clones isolated expressed a major epitope(s) that was immunoreactive with anti‐U1 RNP sera, as shown by several techniques. Affinity‐purified autoantibodies from the cloned RNP protein specifically recognized the 68‐kd U1 RNP protein of HeLa cell nuclear extracts. All sera containing anti‐U1 RNP antibodies detected by immunodiffusion, counterimmuno‐electrophoresis, or immunoblotting also recognized the cloned RNP protein. The RNP antigen‐expressing bacterial colonies and the partially purified cloned RNP fusion protein have been applied to fast and sensitive immunologic assays for the detection and quantification of anti‐U1 RNP antibodies.
A controlled trial comparing sulfasalazine, gold sodium thiomalate, and placebo in rheumatoid arthritis
Authors: Williams H. J. , Ward J. R. , Dahl S. L. , Clegg D. O. , Willkens R. F. , Oglesby T. , Weisman M. H. , Schlegel S. , Michaels R. M. , Luggen M. E. , Polisson R. P. , Singer J. Z. , Kantor S. M. , Shiroky J. B. , Small R. E. , Gomez M. I. , Reading J. C. , Egger M. J.
Published: February 2007

One hundred eighty‐six patients with active rheumatoid arthritis were evaluated in a double‐blind, randomized study that compared treatment with sulfasalazine (SSZ) (2 gm/day), gold sodium thiomalate (GST) (50 mg/week), and placebo (PBO). The 37—week course of therapy was completed by 109 patients. While marked improvement was seen in all 3 treatment groups, the only statistically significant differences between SSZ or GST and PBO were in a decreased erythrocyte sedimentation rate and increased grip strength in the right hand. GST is known to be superior to PBO, and the response of the GST‐treated group was similar to that seen in other trials. The response of the PBO group, however, was much greater than in other placebo groups we have studied. SSZ was similar in efficacy to injectable gold, but was better tolerated. Because of adverse drug reactions (most commonly, rash, stomatitis, and proteinuria), 41% of patients were withdrawn from the GST treatment. Untoward drug effects (most frequently, rash and gastrointestinal distress) caused 16% of patients to be withdrawn from SSZ therapy.
Chondrocalcinosis in surgically resected joints
Authors: Sokoloff Leon , Varma Andre A.
Published: February 2007

To investigate the association between chondrocalcinosis (CC) and osteoarthritis (OA), 338 joint specimens were examined histologically (55 knees and 84 hips surgically resected because of idiopathic OA, 106 control knees obtained postmortem, and 93 fractured hips). The risk for CC in the OA knees was sixfold that of the age‐and sex‐adjusted control sections. CC occurred much less frequently in the hip than in the knee; the association with OA was less clear‐cut. It was not possible to resolve by statistical analysis which of the two pathological processes was the horse and which was the cart.
Antibodies against native type ii collagen do not precede the clinical onset of rheumatoid arthritis
Authors: Möttönen Timo , Hannonen Pekka , Oka Martti , Rautiainen Jaakko , Jokinen Ilmari , Arvilommi Heikki , Palosuo Timo , Aho Kimmo
Published: February 2007

Serum levels of IgG and IgM antibodies to native human type II collagen were determined in 22 pre‐illness sera from subjects who developed seropositive rheumatoid arthritis (RA) 4 months to 5 years after sera were obtained, in 51 specimens from 35 healthy controls, and in 4–5 specimens from 58 patients with recent‐onset RA. The antibody levels in all pre‐illness serum specimens fell within the range seen for the healthy controls. Four RA patients had an IgG class antibody level and 4 had an IgM class antibody level that was above the highest level observed for controls, in at least 1 serum sample. No significant difference in the mean level of anticollagen antibodies was observed in the followup specimens from RA patients.
Comparison of parenteral adrenocorticotropic hormone with oral indomethacin in the treatment of acute gout
Authors: Axelrod David , Preston Stafford
Published: February 2007

One hundred male patients who presented with acute gouty arthritis were alternately assigned to 2 treatment groups. Seventy‐six patients completed the study protocol, in which each gout attack during a 1‐year period was treated. For each gout episode, 36 patients received a single intramuscular injection of 40 IU of adrenocorticotropic hormone (ACTH), and 40 patients received oral indomethacin, 50 mg 4 times daily with meals, until the pain abated. The time interval until the pain was relieved, as well as any untoward effects, were recorded for each gout attack treated. Both groups were of similar age, and had similar values for intercritical serum uric acid, 24‐hour urinary uric acid, and creatinine clearance (1 month after entry into the study). The mean interval (±SD) to relief of pain was significantly shorter for the ACTH group (3 ± 1 hours) than for the indomethacin group (24 ± 10 hours). No side effects were noted in the ACTH group. However, of the 40 patients receiving indomethacin, 22 had abdominal discomfort or dyspepsia, 15 had headaches, and 12 had difficulty with mentation. Single‐dose parenteral ACTH appeared to be effective more rapidly and was associated with fewer side effects than oral indomethacin in the treatment of acute gout.
Treatment of lupus nephritis with total lymphoid irradiation. observations during a 12–79‐month followup
Authors: Strober Samuel , Fariñas M. Carmen , Field Elizabeth H. , Solovera Jose J. , Kiberd Bryce A. , Myers Bryan D. , Hoppe Richard T.
Published: February 2007

Seventeen patients with intractable lupus nephritis and nephrotic syndrome were treated with total lymphoid irradiation. Statistically significant improvement in mean renal disease and serologic activity parameters occurred within 3 months and persisted for at least 3 years. Although there was a marked reduction of T helper cell numbers and function after total lymphoid irradiation, recovery of these parameters was not associated with a return of disease activity. Risks of sterility, severe infections, and hematologic malignancy appeared to be lower than with alkylating agents.
Synovial fluid collagenase in patients with destructive arthritis of the shoulder joint
Authors: Dieppe P. A. , Cawston T. , Mercer E. , Campion G. V. , Hornby J. , Hutton C. W. , Doherty M. , Watt I. , Woolf A. D. , Hazleman B.
Published: February 2007

We studied synovial fluid (SF) collagenase in 10 women with severe rheumatoid arthritis (RA), 10 with pyrophosphate arthropathy, and 10 with idiopathic destructive disease of the shoulder conforming to a pattern recently described. SF cell counts were highest in the RA group. Particles were detected by polarized light microscopy and alizarin red staining. Crystals were seen in fluids from all 3 groups; pyrophosphate predominated in the pyrophosphate arthropathy group and alizarin red—positive particles in the idiopathic disease group. Collagenase and tissue inhibitor of metalloproteinase levels were estimated in SF after gel filtration. Tissue inhibitor of metalloproteinase activity was detected in all fluids, but tended to be highest in the RA group. Collagenase activity was detected in 3 RA fluids only. In no sample was collagenase found in an active form. These findings support the clinical concept of an aggressive destructive process which sometimes occurs in the shoulder joints of elderly women. Because we were not able to detect free collagenase in SF from any of the patients with idiopathic shoulder disease, the data suggest that high levels of active collagenase are not characteristic of this group of patients.
Synovial lymphocyte response to chlamydial stimulation associated with intrasynovial chlamydial antigen in a patient with “rheumatoid arthritis”
Authors: Ford Denys K. , Reid Graham D. , Magge Sathish , Schumacher H. Ralph
Published: February 2007

A 48‐year‐old man with “rheumatoid arthritis” of 3 years duration was found to have synovial fluid lymphocytes that were maximally stimulated in vitro by chlamydial antigen, on 5 of 6 tests over 18 months. Immunocyto‐chemical staining of a synovectomy specimen, using the peroxidase‐antiperoxidase technique, subsequently revealed chlamydial antigen in the synovium. The possibility that Chlamydia in the synovium may produce features of rheumatoid arthritis is discussed.
The efficacy and safety of auranofin in the treatment of juvenile rheumatoid arthritis
Authors: Marcolongo Roberto , Mathieu Alessandro , Pala Riccarda , Giordano Nicola , Fioravanti Antonella , Panzarasa Rita
Published: February 2007

The safety and efficacy of auranofin in the long‐term treatment of children with juvenile rheumatoid arthritis was investigated in an open study of 14 patients. Twelve patients completed at least 12 months of treatment, and 7 patients completed 36 months of treatment. Classic parameters of disease activity showed improvement over baseline values after 6 months of treatment, and laboratory indices remained stable or improved throughout the study. Auranofin was well tolerated; the frequency of adverse effects was lower in these patients than has been previously reported in either adults or children whose arthritis has been treated with injectable gold.
Histologic localization of lipid in the articular tissues in calcium pyrophosphate dihydrate crystal deposition disease
Authors: Ohira Takashi , Ishikawa Koichiro , Masuda Ikuko , Yokoyama Mitsuru , Honda Itsuo
Published: February 2007

We demonstrated the histologic localization of lipid in the articular cartilage, meniscus, and synovium in calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, by staining with Sudan III. Almost all the sites of tophus‐like deposits of CPPD crystals and the degenerated matrix containing low concentrations of scattered CPPD crystals stained strongly with Sudan III. Transmission electron microscopy demonstrated round or oval lipid droplets in more than half of the chondrocytes around the crystals in each of these tissues. Small lipid droplets were also seen on or around the crystals. These findings suggest that lipids are abundant at the site of CPPD crystal deposition and may be involved in CPPD crystal formation.
Sulfasalazine in the treatment of ankylosing spondylitis
Authors: Nissilä M. , Lehtinen K. , Leirisalo‐Repo M. , Luukkainen R. , Mutru O. , Yli‐Kerttula U.
Published: February 2007

Eighty‐five patients with active ankylosing spondylitis (AS) were randomized to receive either sulfasalazine (≤3 gm/day, mean 2.5) or placebo for 26 weeks. There was a statistically significant improvement, compared with baseline, in most of the clinical variables in patients receiving the active drug. Laboratory parameters (erythrocyte sedimentation rate, C‐reactive protein, IgG, IgM, and IgA) also improved during the active treatment, suggesting a beneficial effect of sulfasalazine on AS. At the end of the treatment, significant differences between the sulfasalazine and placebo groups were observed in morning stiffness, chest expansion, erythrocyte sedimentation rate, and in all immunoglobulin classes. Two patients in each treatment group discontinued the trial because of side effects. Enteric‐coated sulfasalazine seemed to be effective and well tolerated in patients with active AS.
The diagnosis of polyarteritis nodosa
Authors: Albert Daniel A. , Silverstein Marc D. , Paunicka Kathryn , Reddy Geetha , Chang Rowland W. , Derus Charles
Published: February 2007

We evaluated our literature‐based estimates of diagnostic test characteristics and aggressive and conservative strategies for the diagnosis of polyarteritis nodosa (PAN) by reviewing 1980 through 1985 data from the University of Chicago Medical Center, Michael Reese Hospital, and Northwestern University Medical School. Test specificity was calculated by reviewing pathology and radiology reports on all relevant procedures done at the University of Chicago Medical Center in 1984 and 1985. There were no reports of false‐positive findings (including angiography); thus, test specificity was 100% for muscle, nerve, kidney, liver, and testicular biopsy, which was comparable with our literature‐based estimate of 97%. Test sensitivity was based on the 18 confirmed cases of PAN from the 3 institutions and was similar to that in published reports, ranging from 0% for liver biopsy to 100% for visceral angiography. Review of each case for diagnostic test sequence showed an average of 2 diagnostic procedures to confirm the diagnosis (range 1–6). Eight of 18 patients were evaluated according to the conservative strategy we proposed from our literature‐based decision analysis approach. No patient was evaluated with the aggressive strategy, although 1 patient had 6 invasive procedures. Of the remaining 10 patients, 9 represented cases that might have been confirmed had the conservative approach been used, and if it had been used, 6 patients would have had the diagnosis confirmed. Thus, the minimum sensitivity of our conservative strategy is 78%, although based on these data, it could be as high as 100%. Our findings suggest that an effective diagnostic approach to the patient with suspected PAN is first serologic and biochemical evaluation, followed by electromyography and nerve conduction velocity to localize symptomatic muscle and nerve involvement. Invasive testing should include muscle and/or nerve biopsy for those with symptomatic sites; if these show negative findings, visceral angiography should be performed. If there is no symptomatic site, visceral angiography should be performed; if the findings are negative, blind muscle biopsy should be performed. Testicular biopsy should be considered if the patient is symptomatic, although there are presently too few data about this procedure to recommend it without qualification. This conservative strategy appears to maximize the accuracy and minimize the cost and morbidity of the investigation.
Suppression of streptococcal cell wall–induced arthritis by a potent protease inhibitor, bis(5‐amidino‐2‐benzimidazolyl)methane
Authors: Dieter Geratz J. , Pryzwansky Katherine B. , Schwab John H. , Anderle Sonia K. , Tidwell Richard R.
Published: February 2007

Bis(5‐amidino‐2‐benzimidazolyl)methane, a powerful synthetic trypsin inhibitor, proved to be highly effective in suppressing the arthritis induced by streptococcal cell wall fragments in Lewis rats. It reduced not only the degree of synovitis, osteitis, and hematopoietic hyperplasia in the distal extremities, but also the degree of associated granulomatous inflammation in the liver. The results suggest that trypsin‐like proteases play an important role in this arthritis model and that inhibitors may be useful in the treatment of similar arthritic conditions in humans.
Heterogeneous synthetic phenotype of cloned scleroderma fibroblasts may be due to aberrant regulation in the synthesis of connective tissues
Authors: Whiteside Theresa L. , Ferrarini Marina , Hebda Patricia , Buckingham Robert B.
Published: February 2007

Clones of dermal fibroblasts from the skin of 4 normal subjects and 5 patients with progressive systemic sclerosis (PSS; scleroderma) were established, and their synthetic and proliferative characteristics were compared. A limiting‐dilution assay was used to determine frequencies of cloning in the microcultures of dermal fibroblasts plated. The clones derived from single cells were expanded in vitro and examined (in passages C–H) for growth and synthesis of glycosaminoglycan (GAG) and collagenase‐sensitive protein (CSP). The clonogenicity of PSS fibroblasts was not significantly different from that of normal fibroblasts. Normal fibroblast clones were characterized by low levels of GAG and CSP synthesis, and there was a correlation between the GAG and CSP phenotypes. In contrast, clones of PSS fibroblasts were often, but not always, high producers of GAG and CSP, but there was no correlation between the levels of GAG and CSP synthesis. It appears that scleroderma skin is composed of fibroblast clones that are unable to regulate the synthesis of connective tissue components and often synthesize large amounts of connective tissue macromolecules.
Progressive ankylosis in mice
Authors: Mahowald Maren L. , Krug Hollis , Taurog Joel
Published: February 2007

To determine its similarity to human spondylarthropathies, we studied murine progressive ankylosis, a spontaneously occurring disorder of joints in mice. Clinically, peripheral joints were inflamed initially, then became ankylosed in a predictable sequence from distal to proximal. Forefeet were involved before hindfeet. Axial joint involvement produced severe spinal ankylosis. Extraarticular manifestations included balanitis and crusting skin lesions. Radiographically, bony erosions and calcification of articular and periarticular tissues were extensive, and vertebral syndesmophytes produced a “bamboo” spine. We conclude that progressive ankylosis is a systemic disease with many clinical and radiographic similarities to human spondylarthropathies, and it may represent a useful animal model for the study of the human diseases.
Histopathologic findings in the liver of rheumatoid arthritis patients treated with long‐term bolus methotrexate
Authors: Aponte Julio , Petrelli Mary
Published: February 2007

Twenty‐three patients with severe rheumatoid arthritis were treated with oral methotrexate (MTX) for more than 10 years. MTX was given as a bolus of 5–15 mg/week; the total cumulative dose ranged from 4,690 mg to 10,230 mg. Liver biopsies were performed on 21 of the patients to assess possible fibrosis and cirrhosis. Grade I histopathologic changes were found in 13 of the 21 biopsy samples, grade II changes were found in 3, and grade HIA changes (mild fibrosis) were found in 5 specimens. None of the biopsy samples showed cirrhosis. Repeat biopsies were performed on the 5 patients with grade IIIA changes while they were still taking MTX. No progression of the fibrosis was noted. Two of the 5 samples, however, were graded IIIB because of portal and perilobular inflammation. Our findings support the premise that prolonged administration of oral MTX, when given as a weekly bolus at a low dose, does not cause cirrhosis or severe fibrosis in the rheumatoid arthritis patient who does not abuse alcohol.
Changes in b lymphocyte function in rheumatoid arthritis and lupus nephritis after total lymphoid irradiation
Authors: Solovera J. J. , Fariñas M. C. , Strober S.
Published: February 2007

Patients with rheumatoid arthritis and patients with lupus nephritis underwent total lymphoid irradiation (TLI). Peripheral blood mononuclear cells from these patients showed a decrease in pokeweed mitogen—induced immunoglobulin secretion after TLI. A defect in non‐T cells contributed to the decreased response. No defect in the response of non‐T cells to T cell—independent activators of B cells, Staphylococcus aureus Cowan 1 and Epstein‐Barr virus, was observed after TLI. We conclude that TLI induces a selective deficit in B cells, which respond to T cell—dependent mitogen stimulation.
Actions of recombinant human γ‐interferon and tumor necrosis factor α on the proliferation and osteoblastic characteristics of human trabecular bone cells in vitro
Authors: Gowen Maxine , Macdonald Brian R. , Graham R. , Russell G.
Published: February 2007

Using cultured human osteoblast‐like cells, we studied the effects of tumor necrosis factor (TNF) and recombinant human γ‐interferon (γ‐IFN) on osteoblast growth and function, and demonstrated that TNF stimulated bone cell proliferation and prostaglandin production while inhibiting 1,25‐(OH)2D3—stimulated alkaline phosphatase activity and osteocalcin release. In contrast, γ‐IFN inhibited proliferation and stimulated alkaline phosphatase activity of the cells, while inhibiting 1,25‐(OH)2D3—stimulated osteocalcin production and having variable effects on the release of prostaglandins, depending on the presence of other factors. Our results suggest that TNF and γ‐IFN can act directly on bone‐forming cells to affect both their proliferation and their differentiated function, and that changes in the ability of cells to produce these factors in disease states may contribute to alterations in the integrity of connective tissue matrices.
Reduced natural killer cell activity in patients with systemic sclerosis
Authors: Miller Edward B. , Hiserodt John C. , Hunt Laverne E. , Steen Virginia D. , Medsger Thomas A.
Published: February 2007

Natural killer (NK) cell number and function were determined in 69 systemic sclerosis (SSc) patients (41 with diffuse cutaneous SSc, 24 with limited cutaneous SSc, and 4 with scleroderma in an overlap syndrome). The results were compared with those obtained from 5 patients with Raynaud's disease and from 27 normal controls. Natural and antibody‐dependent killing was reduced in the total group of SSc patients compared with controls, but these differences were primarily attributable to patients with the diffuse form of the disease who were seen early in their illness (<5 years after onset). NK cell numbers were not significantly reduced in patients compared with controls, although lower numbers were observed in individuals with early diffuse disease. Other clinical parameters, such as treatment with D‐penicillamine or the presence of scleroderma‐specific autoantibodies, did not exert an independent effect on NK cell function. These findings suggest a possible central role for NK cells in the pathogenesis of SSc.
Suppression of monosodium urate crystal—induced acute inflammation by diets enriched with gamma‐linolenic acid and eicosapentaenoic acid
Authors: Tate Guillermo A. , Mandell Brian F. , Karmali Rashida A. , Laposata Michael , Baker Daniel G. , Schumacher H. Ralph , Zurier Robert B.
Published: February 2007

A subcutaneous air pouch formed in Sprague‐Dawley rats was used to study the effect of diets enriched in γ‐linolenic acid (GLA) (in plant seed oil) and eicosapentaenoic acid (EPA) (in fish oil) on acute inflammation induced by monosodium urate crystals. The GLA‐enriched diet suppressed significantly the cellular phase of inflammation (polymorphonuclear leukocyte accumulation, crystal phagocytosis, and lysosomal enzyme activity), but it had little effect on the fluid phase (exudate volume and protein concentration). In contrast, the EPA‐enriched diet suppressed the fluid phase but not the cellular phase of inflammation. The findings indicate that the fluid and cellular phases of acute inflammation can be controlled independently. A combined diet of fish oil and plant seed oil (EPA‐enriched and GLA‐enriched) reduced both the cellular and fluid phases of inflammation. Thus, dietary provision of alternative substrates for oxidative metabolism (other than arachidonic acid) modifies monosodium urate crystal‐induced acute inflammation.
Effects of gold sodium thiomalate and tenidap sodium (CP‐66,248–2) on a model of macrophage differentiation using HL‐60 cells
Authors: Littman Bruce H. , Carlson Patricia L. , Loose Leland D. , Sanders Karen M.
Published: February 2007

We studied the effects of gold sodium thiomalate (GST) and a new antirheumatic drug, tenidap sodium ([Z]‐5‐chloro‐2,3‐dihydro‐3‐[hydroxy‐2‐thienylmethylene]‐2‐oxo‐1H‐indole‐1‐carboxamide, sodium salt), previously known as CP‐66,248–2, in a model system of macrophage differentiation using a myelomonocytic cell line. HL‐60 cells can be stimulated by vitamin D3 to differentiate along a monocytic pathway. Monocytic HL‐60 cells express CD14 (Leu‐M3), a macrophage surface marker, and develop the capacity to produce the second complement component (C2) in response to stimulation with cytokines such as γ‐interferon. The effects of GST and tenidap sodium were compared with the effects of dexamethasone and a variety of nonsteroidal antiinflammatory drugs in this model system. We found that GST inhibited the capacity of HL‐60 cells to produce C2 but did not inhibit the expression of CD14. Tenidap sodium inhibited C2 production as well as CD14 expression, and it partially reversed the decrease in 3H‐thymidine incorporation by HL‐60 cells, which accompanies monocytic differentiation. At concentrations that inhibited C2 production by HL‐60 cells, tenidap sodium did not inhibit C2 production by monocytes. Neither dexamethasone nor the other nonsteroidal antiinflammatory drugs tested possessed these activities. Thus, both GST and tenidap inhibit markers of monocytic differentiation in HL‐60 cells, and this activity may relate to their antirheumatic activities.
Iodide and albumin kinetics in normal canine wrists and knees
Authors: Simkin Peter A. , Benedict Richard S.
Published: February 2007

The clearance rates of free iodide and of radioiodinated serum albumin were measured in the knee and wrist joints of 9 normal adult dogs. Iodide clearance from the knee was 3 times greater than that from the wrist. In contrast, radioiodinated serum albumin clearance from the knee was only slightly greater than that from the wrist. Interpreted as respective indices of effective synovial plasma flow and lymphatic drainage, these values indicate that the filtration fraction is normally greater in microvessels of the wrist than in those of the knee. These findings complement the results of companion studies of Starling forces that indicate a higher pressure microvascular bed in the wrist than in the knee.
Reduction of the risk of rheumatoid arthritis among women who take oral contraceptives
Authors: Hazes Johanna M. W. , Dijkmans Ben A. C. , Vandenbroucke Jan P. , De Vries René R. P. , Cats Arnold
Published: February 2007

Discrepant results among investigations of the association between oral contraceptive use and rheumatoid arthritis (RA) have been ascribed to shortcomings in the study methods. In the present study, we obtained detailed information on oral contraceptive use in 135 young women with confirmed definite or classic RA of recent onset and in 378 controls with soft tissue rheumatism or osteoarthritis. All patients had at least 2 years of followup to confirm the consistency of the diagnosis. Oral contraceptive use at any time before disease onset was reported by 70% of the RA patients and 85% of the controls; the latter figure corresponded to general population data for The Netherlands. This yielded a relative risk for RA of 0.39 among those who had ever used oral contraceptives and 0.58 for those using oral contraceptives at the time of symptom onset. The preventive effect of oral contraceptive use on the risk of RA was found to be independent of the dose, duration of use, or presence of HLA‐DR4. The strongest protection was seen in women with a family history of RA and in women ages 31–40 at symptom onset. The conflicting results in the literature are discussed, and a possible biologic mechanism for this phenomenon is suggested.
Antibodies from patients with rheumatoid arthritis and systemic lupus erythematosus recognize different epitopes of a single heterogeneous nuclear rnp core protein
Authors: Montecucco Carlomaurizico , Caporali Roberto , Negri Claudia , Gennaro Fabio De , Cerino Antonella , Bestagno Marco , Cobianchi Fabio , Astaldi‐Ricotti Giulia C. B.
Published: February 2007

Antibodies to recombinant heterogeneous nuclear RNP core protein A1 were detected in sera from 27 of 58 patients with rheumatoid arthritis (RA) and from 7 of 31 patients with systemic lupus erythematosus, by immunoblotting and enzyme‐linked immunosorbent assay. Protein A1 consists of 2 distinct domains: The N‐terminal sequence is identical to a single‐stranded DNA binding protein termed UP1, and the Ckerminal domain shows a partial homology with keratin. All 7 Al‐positive systemic lupus erythematosus sera reacted with UP1, whereas 9 of the 27 Al‐positive RA sera did not. In RA, anti‐A1 activity was significantly associated with antikeratin antibodies (AKA); these antibodies were present in 23 of 27 Al‐positive sera and 10 of 31 Al‐negative sera (P > 0.01). Immunoabsorption with recombinant protein A1 resulted in a significant reduction of AKA titers in 6 of 10 RA sera tested, suggesting that AKA from RA patients may cross‐react with the C‐terminal portion of the heterogeneous nuclear RNP protein Al.
Monoclonal antibody 6b6.6 defines a cross‐reactive kappa light chain idiotope on human monoclonal and polyclonal rheumatoid factors
Authors: Schrohenloher Ralph E. , Accavitti Mary Ann , Bhown Ajit S. , Koopman William J.
Published: February 2007

Mouse monoclonal antibody (MAb) 6B6.6 was raised against a cross‐reactive idiotope (CRI) present on the light chains of 2 human IgM paraproteins with rheumatoid factor (RF) activity. The MAb inhibited the IgG‐binding activity of these proteins, and thus appears to react with an epitope located at or near the RF‐binding site. Enzyme‐linked immunosorbent assay (ELISA) and Western immunoblotting studies indicate that the 6B6.6 CRI is associated with kIIIa sub‐subgroup light chains, is not related to the Wa, Po, and Bla RF cross‐idiotypic specificities, and is clearly distinct from the kIIIb‐associated CRI detected by MAb 17.109. Using an ELISA, we detected 6B6.6 CRI in 59% of 107 sera and 48% of 50 synovial fluids from patients with seropositive rheumatoid arthritis (RA). However, the quantities of CRI‐positive RF were small, and the amount of CRI‐positive RF did not correlate with the amount of IgM‐RF. The 6B6.6 CRI was shown to occur primarily in the IgM fraction of RA sera by both chromatographic studies and isotype‐specific ELISA, although small quantities appeared to be associated with IgA and IgG in some sera. The presence of 6B6.6 CRI on both monoclonal and polyclonal RF is consistent with the view that both are derived, at least in part, from a common gene pool. However, its occurrence in relatively low levels suggests that the number of germline genes encoding for RF is large or that extensive mutation occurs in the course of RF expression in RA.
Interleukin‐1 release by rat synovial cells is dependent on sequential treatment with γ‐interferon and lipopolysaccharide
Authors: Johnson William J. , Breton John , Newman‐Tarr Tonie , Connor Janice R. , Meunier Paul C. , Dalton Barbara J.
Published: February 2007

To determine the potential regulatory mechanisms involved in synovial cell interleukin‐1 (IL‐1) release, the ability of γ‐interferon (γ‐IFN) to influence IL‐1 release was assessed. Rat synovial cells cultured in the presence of a variety of stimuli, including lipopolysaccharide (LPS), failed to release IL‐1. However, pretreatment of synovial cells with γ‐IFN, followed by LPS stimulation, resulted in increased levels of intracellular IL‐1 as well as release of IL‐1 from the cell. The level of IL‐1 release was dependent on the concentration of both γ‐IFN and LPS, and on length of exposure to the γ‐IFN. The kinetic and dose requirements for γ‐IFN‐dependent IL‐1 release were similar to those for Ia antigen expression, but LPS was necessary for IL‐1 messenger RNA induction, intracellular IL‐1 accumulation, and IL‐1 release. In addition, sequential treatment, i.e., γ‐IFN followed by LPS, was essential for IL‐1 induction. Substitution of phorbol ester or calcium ionophore for γ‐IFN did not result in similar IL‐1 release. In addition, induction of IL‐1 messenger RNA by another stimulus was not sufficient to result in IL‐1 release following LPS treatment. These results suggest that release of IL‐1 by rat synovial cells requires the production of a regulatory signal, which is inducible by γ‐IFN.
Dna autosensitivity in two japanese sisters
Authors: Sugai Susumu , Yasuda Yukio , Shimizu Shiro , Sawada Makoto , Tachibana Junko , Konda Susumu , Kitada Hirohisa , Nakaizumi Hiroko , Tsukada Sadao
Published: February 2007

Two cases of DNA autosensitivity in Japanese sisters are reported. Both patients developed painful ecchymoses and other bleeding disorders. Skin tests with autologous leukocyte lysates and calf thymus DNA produced intermediate‐type reactions that were identical to spontaneous skin reactions. Pretreatment of DNA with either DNase or chloroquine sulfate inhibited these reactions. Our studies suggest that anti‐DNA antibodies might contribute to the clinical symptoms of this disorder.
The relationship between cd5‐expressing b lymphocytes and serologic abnormalities in rheumatoid arthritis patients and their relatives
Authors: Youinou P. , Mackenzie L. , Katsikis P. , Merdrignac G. , Isenberg D. A. , Tuaillon N. , Lamour A. , Le Goff P. , Jouquan J. , Drogou A. , Muller S. , Genetet B. , Moutsopoulos H. M. , Lydyard P. M.
Published: February 2007

The influence of genetic factors on the expression of CD5+ B lymphocytes and their relationship to a broad spectrum of autoantibodies was investigated in a study of 12 patients with rheumatoid arthritis (RA) and 52 of their healthy first‐degree relatives. The proportion of CD5+ B cells was significantly higher in RA patients (mean ± SEM 23.9 ± 2.7%) compared with that in their relatives (18.3 ± 1.1%; P < 0.05) and compared with that in a group of healthy control subjects (16.1 ± 1.8%; P < 0.05). Much more striking, however, were the high levels of CD5+ B cells found in the patients and their relatives in 5 of the families studied. Increases in total immunoglobulin levels and autoantibody levels were frequently observed in RA patients (∼20–40%) and their relatives (∼10–20%). Furthermore, a statistically significant correlation (P < 0.01) between IgM rheumatold factor and the percentage of B lymphocytes expressing CD5 was observed.
Enhanced binding of lupus sera to the polyamine‐induced left‐handed z‐dna form of polynucleotides
Authors: Thomas T. J. , Meryhew Nancy L. , Messner Ronald P.
Published: February 2007

The natural polyamines putrescine, spermidine, and spermine are small polyvalent cations present in all living cells. Spermidine and spermine are excellent promoters of left‐handed Z‐DNA, an immunogenic form of DNA that binds readily with anti‐DNA antibodies in the sera of patients with systemic lupus erythematosus (SLE). We studied the binding of a panel of 16 SLE sera to poly(dA‐dC) poly(dG‐dT) and poly(dG‐m5dC).poly (dG‐m5dC) in the presence and absence of spermidine and spermine using an enzyme‐linked immunosorbent assay. The majority of SLE sera showed a 50–150% mean increase in optical density values when incubated with the polynucleotides and either 0.25 mM spermidine or 0.025 mM spermine than when incubated with the polynucleotides alone. Under these conditions, the polynucleotides assumed the Z‐DNA form. Since polyamines are ubiquitous cellular components and since potential Z‐DNA‐forming alternating purine‐pyrimidine sequences are widely dispersed in native DNA, the increased binding of SLE sera to polyamine‐induced Z‐DNA suggests a pathogenic role for these compounds in SLE.
Soluble interleukin‐2 receptors in patients with systemic sclerosis
Authors: Degiannis Dimitrios , Seibold James R. , Czarnecki Margaret , Raskova Jana , Raska Karel
Published: February 2007

Plasma levels of soluble interleukin‐2 receptors (sIL‐2R) were measured by an enzyme‐linked immunosorbent assay in 79 patients with systemic sclerosis (SSc). These levels were significantly elevated in SSc patients, compared with normal controls (mean ± SEM 866.0 ± 63.6 units/ml versus 293.0 ± 20.5; P < 0.001). Soluble IL‐2R levels were highest in patients with generalized disease, were strongly associated with mortality (P < 0.001) and inversely correlated with disease duration (P = 0.003), but were not related to sex, age, specific visceral involvement, serologic status, peripheral lymphocyte count, or therapy. Levels of sIL‐2R in the supernatants of peripheral blood mononuclear cells were low in patients and controls, and showed comparable increases following phytohemagglutinin stimulation. Exposure of peripheral blood mononuclear cells to laminin did not induce sIL‐2R release. Circulating IL‐2 levels were comparably low in patients and controls. Our findings suggest the presence of lymphocyte activation in SSc, and further suggest that measurement of sIL‐2R may prove to be a useful laboratory technique for assessing disease activity.
Analysis of improvement in individual rheumatoid arthritis patients treated with disease‐modifying antirheumatic drugs, based on the findings in patients treated with placebo
Authors: Paulus Harold E. , Egger Marlene J. , Ward John R. , James Williams H.
Published: February 2007

A composite index for estimating improvement in individual rheumatoid arthritis (RA) patients during trials of slow‐acting, disease‐modifying antirheumatic drugs (DMARDs) was developed by analyzing the responses of 130 placebo‐treated participants in Cooperative Systematic Studies of Rheumatic Diseases studies. If responses in 4 of 6 selected measures were required for improvement (by ⩾20% for morning stiffness, Westergren erythrocyte sedimentation rate, joint pain/tenderness score, and joint swelling score, and by ⩾2 grades on a 5‐grade scale, or from grade 2 to grade 1 for patient's and physician's overall assessments of current disease severity), few placebo‐treated patients qualified as improved, whereas significantly more DMARD‐treated patients demonstrated improvement. The proposed index appears to be useful in estimating the probability that an RA patient will improve if taking a placebo during a DMARD trial, and may be a useful tool for analysis of DMARD studies.
C3 activation products correlate with antibodies to lipid a in pauciarticular juvenile arthritis
Authors: Olds Lynne C. , Miller John J.
Published: February 2007

IgM antibodies to monophosphoryl‐lipid A were found to be elevated in sera from children with all forms of juvenile arthritis (JA) and systemic lupus erythematosus. Of more interest, in patients with pauciarticular JA, IgG antibody titers to monophosphoryl‐lipid A were found to be correlated with the C3a concentration and the C3d:C3 ratio. Although the full specificity of these antibodies is unknown, they are the first that have been found to be correlated with complement activation products in any form of JA.
Septic arthritis
Authors: Williams Riley J. , Lane Smith R. , Schurman David J.
Published: February 2007

We report herein that cartilage proteolytic activity increased in bovine and rabbit articular cartilage after treatment with a purified staphylococcal culture medium or intraarticular infection with Staphylococcus aureus. Staphylococcal culture medium increased the release of gelatinolytic, collagenolytic, and caseinolytic activity into the medium of isolated chondrocytes or cartilage organ culture. The proteolytic activities were determined in assays using radiolabeled substrate and sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. Staphylococcal culture medium was proteolytically inactive by both assay techniques. RNA synthesis of isolated chondrocytes was unaffected by staphylococcal culture medium, whereas overall protein synthesis was inhibited by 84%. An analysis of extracts of Staphylococcus aureus‐infected rabbit knee cartilage by substrate gels showed increased gelatinolytic and caseinolytic activity compared with extracts of uninfected knee cartilage. Our data suggest that the rapid loss of proteoglycan and persistent degradation of cartilage in staphylococcal septic arthritis is due to the production and activation of chondrocyte proteases.
Ly‐1 b cells and disease activity in (new zealand black × new zealand white)f1 mice
Authors: Carmen Fariñas M. , Stall Alan M. , Solovera Jose J. , Tarlinton David M. , Herzenberg Lenore A. , Strober Samuel
Published: February 2007

The treatment of female (New Zealand black × New Zealand white)F1 mice with total lymphoid irradiation resulted in a prolonged remission of autoimmune disease activity. Total lymphoid irradiation‐treated mice also showed a marked reduction of Ly‐1 B cells, which lasted up to 3 months. The subsequent return of Ly‐1 B cells to preirradiation levels was not associated with a simultaneous return of disease when measured by parameters such as IgG anti‐DNA antibodies and spontaneous secretion of IgG by splenic cells. In cell sorting experiments, most of the cells spontaneously secreting IgG were found within the Ly‐1‐ (CD5‐) splenic B cell population.
Association of scleroderma with a t cell antigen receptor γ gene restriction fragment length polymorphism
Authors: Kratz Lisa E. , Boughman Joann A. , Pincus Theodore , Cohen David I. , Needleman Barbara White
Published: February 2007

Restriction fragment length polymorphisms (RFLPs) in the T cell receptor (TCR) α, β, and γ genes were analyzed in 61 scleroderma patients and 150 controls. An association was found between scleroderma and an 11.3‐kb Pvu II fragment in the TCR γ gene; this gene was found in 41.0% of the patients, compared with 21.7% of the controls (P < 0.01, odds ratio = 2.50). There were no associations between scleroderma and the tested RFLPs in the TCR α or β genes, and no RFLPs were found in the constant region of the TCR δ gene.
Relationship between clinical efficacy and laboratory correlates of inflammatory and immunologic activity in rheumatoid arthritis patients treated with nonsteroidal antiinflammatory drugs
Authors: Cush John J. , Jasin Hugo E. , Johnson Regina , Lipsky Peter E.
Published: February 2007

Eighteen rheumatoid arthritis (RA) patients, who had been treated with nonsteroidal antiinflammatory drugs (NSAIDs) only, were enrolled in a 12‐week, open‐label, randomized protocol to determine whether clinical responses might be associated with improvement in laboratory measures of inflammation and immunologic activity in RA patients treated with NSAIDs. Following a 2‐week drug washout period, patients were given either long‐acting ibuprofen (2,400 mg/day) or flurbiprofen (200 mg/day); clinical, laboratory, and immunologic assessments were done biweekly for 10 weeks. A clinical efficacy index, utilizing a combination of measures of disease activity, identified 7 “responders” and 10 “nonresponders” (1 patient discontinued therapy because of a rash). Flow cytometric analysis revealed no abnormalities in the numbers of circulating CD3+, CD4+, or CD8+ lymphocytes in the 17 patients. The density of these T cell markers at enrollment was similar in patients and control subjects. However, following the 2‐week drug washout, significant worsening of morning stiffness, erythrocyte sedimentation rate (ESR), and C‐reactive protein (CRP) was accompanied by a significant decrease (P ⩾ 0.05) in the density of these T cell surface determinants, as is characteristic of activated T cells. After 10 weeks of NSAID therapy, increased density of CD3, CD4, and CD8 was observed in 47%, 73%, and 50% of the patients, respectively. However, in only the responders was the density of these T cell surface markers increased significantly (P ⩾ 0.04). The responders, but not the nonresponders, also demonstrated significant reductions in the ESR, CRP level, serum IgM rheumatoid factor (RF) titer, and spontaneous synthesis of RF by lymphocytes in vitro (P ⩾ 0.05). There were significant correlations between improvements in the clinical parameters (50‐foot walk time, joint score, and global assessment) and reductions in the ESR, CRP level, and serum RF titer (P ⩾ 0.05). These findings demonstrate that clinical improvement in RA patients treated with NSAIDs may be associated with the disappearance of phenotypically activated circulating T cells and functionally activated B cells, as well as with reductions in acute‐phase reactants and serum RF titers.
B cell infiltration of the thymic medulla in new zealand black, new zealand white, and (new zealand black × new zealand white)f1 mice
Authors: Carmen Fariñas M. , Adkins Becky , Stall Alan M. , Weissman Irving , Strober Samuel
Published: February 2007

Thymuses from female (New Zealand black × New Zealand white)F1 ([NZB × NZW]F1), New Zealand black, and New Zealand white mice of different ages were examined by immunohistochemical and flow cytometric analysis. Two‐and‐a‐half‐month‐old (NZB × NZW)F1 mice showed infiltration of the thymus with B cells, and by 6–8 months of age, showed a disruption of the entire medullary area. More than 80% of the thymic B cells had the phenotypic characteristics of conventional B cells (IgM+, IgD+, Ly‐1—). Total lymphoid irradiation induced a marked depletion of medullary B cells and a restoration of the thymic architecture.
A randomized controlled trial of ciamexon versus placebo in the immunomodulatory treatment of rheumatoid arthritis
Authors: Baerwald Christoph , Goebel Klaus‐M. , Krause Andreas , Heymanns Jochen
Published: February 2007

To determine the efficacy of the new immunosuppressive agent ciamexon in patients with rheumatoid arthritis (RA), we conducted a 6‐month, prospective, double‐blind, placebo‐controlled study. The study included 21 outpatients with confirmed RA, who were randomized into 3 treatment groups of 7 patients each. Group 1 received 400 mg/day of ciamexon, group 2 received 100 mg/day of ciamexon, and group 3 received placebo. We investigated the influence of ciamexon on the clinical course, the systemic inflammatory activity, and the lymphocyte subsets in the peripheral blood. Significant, dose‐dependent improvement was seen in both the clinical and the biochemical activity indexes at the end of the treatment period (P = 0.02 to P = 0.05). The proportion of activated T lymphocytes was significantly decreased (P = 0.05), and the proportion of CD8‐positive lymphocytes was significantly increased (P = 0.03) in patients taking ciamexon. The major adverse effects were hepatotoxicity (2 patients) and rash (2 patients). This study documents the clinical efficacy of ciamexon therapy in RA patients and identifies the agent's potential toxicity.
Signal measurement strategies: are they feasible and do they offer any advantage in outcome measurement in osteoarthritis?
Authors: Bellamy Nicholas , Watson Buchanan W. , Goldsmith Charles H. , Campbell Jane , Duku Eric
Published: February 2007

The applicability of a signal measurement strategy was compared with a traditional method of measuring outcome in osteoarthritis. The signal method detected statistically significant alterations in health status with small sample sizes and with a relative efficiency close to or at unity. The prevalence of deterioration in nonsignal items was low. Signal methods of measurement may provide an alternative approach to outcome measurement in osteoarthritis clinical trials.
Importance of the IgG isotype, not the state of glycosylation, in determining human rheumatoid factor binding
Authors: Newkirk Marianna M. , Lemmo Antonina , Rauch Joyce
Published: February 2007

We investigated the influence of carbohydrate on the binding of human rheumatoid factors (RF) to the Fc fragment of IgG. The monoclonal RF studied were derived from the serum of patients with mixed cryoglobulinemia or from hybridomas generated from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus. Polyclonal RF were derived from patients with RA. The carbohydrate located on the Fc fragment, regardless of whether it contained different amounts of mannose or reduced amounts of galactose, or was removed, did not affect the binding of the RF. In contrast, the isotype of the Fc was found to be critical. Two groups of hybridoma RF could be delineated. One group bound preferentially to IgG1 and/or IgG2, and a second group (primarily from patients with RA) bound preferentially to IgG3 and/or IgG4. Our results indicate that the isotype of the Fc fragment, and not the extent of galactosylation, influences the binding of the RF.