bluuebunny/crossref_metadata_2025 huggingface dataset:
Occurrence of ankylosing spondylitis in a nationwide series of twins
Authors: JÄRvinen Pentti
Published: February 2007

Objective. To obtain information on the rate of concordance for ankylosing spondylitis (AS) in a population‐based series of twins.

Methods. AS cases were identified by record linkage of the population‐based Finnish Twin Cohort and the nationwide registry for fully reimbursed medications. A clinical examination was performed to establish concordance for AS.

Results. There were 6 monozygotic (MZ) pairs and 20 dizygotic (DZ) pairs with at least 1 member affected by AS. Three MZ pairs and 3 DZ pairs were concordant for the disease. All affected subjects were HLA‐B27 positive. The pairwise concordance rate was 50% in MZ twins and 20% in HLA‐B27 positive DZ twins (95% confidence intervals 11.8–88.2% and 4.3%–48.1%, respectively).

Conclusion. These results indicate that AS disease expression is largely, but not entirely, genetically based, with a gene or genes other than B27 probably playing a role.
Selective induction of igm rheumatoid factors by cd14+ monocyte‐lineage cells generated from bone marrow of patients with rheumatoid arthritis
Authors: Hirohata Shunsei , Yanagida Tamiko , Koda Michinobu , Koiwa Masahito , Yoshino Shin'Ichi , Ochi Tkahiro
Published: February 2007

Objective. To determine the capacity of CD14+ monocyte‐lineage cells induced from bone marrow of rheumatoid arthritis (RA) patients to stimulate the production of IgM rheumatoid factor (IgM‐RF), in order to explore the functional abnormalities of CD14+ cells and gain insight into the mechanism of selective synthesis of IgM‐RF in RA.

Methods. CD14+ cells were induced by granulocyte–macrophage colony‐stimulating factor (GM‐CSF) stimulation of CD14– cells purified from bone marrow cells obtained from 6 RA patients and 6 osteoarthritis (OA) patients. The production of IgM and IgM‐RF was induced by stimulating B cells from normal healthy individuals with immobilized anti‐CD3‐activated autologous CD4+ T cells. The effects of CD14+ cells on the proportion of IgM‐RF to total IgM produced by the normal B cells were assessed.

Results. CD14+ cells induced by GM‐CSF stimulation of bone marrow CD14– cells from the 6 RA patients significantly enhanced the proportion of IgM‐RF to total IgM produced by anti‐CD3‐activated CD4+ T cell‐stimulated normal B cells (P < 0.05), whereas GM‐CSF–induced CD14+ cells from the bone marrow of the 6 OA patients did not significantly affect IgM‐RF production. CD14+ cells induced by GM‐CSF obtained from different sites in the same RA patient on different occasions consistently enhanced the proportion of IgM‐RF to IgM produced by B cells from different normal subjects.

Conclusion. These results indicate that abnormal CD14+ monocytes stimulate RF‐producing B cells to be ready to be activated by the signals delivered through noncognate TßB interactions with anti‐CD3‐activated T helper cells. Moreover, the data suggest that the accelerated generation of such functionally abnormal CD14+ cells from bone marrow precursors might play an important role in the pathogenesis of RA.
The role of the immunoglobulin heavy chain in human anti‐dna antibody binding specificity
Authors: Mahmoudi Ahmoud , Denomme Gregory A. , Edwards Jane Y. , Bell David A. , Cairns Ewa
Published: February 2007

Objective. To investigate the structural basis for DNA binding of the natural human IgMλ monoclonal antibody KIM4.6.

Methods. An IgMλ, non–DNA‐reactive variant hybridoma was derived during in vitro subcloning of the anti‐DNA antibody KIM4.6. The variable (V)‐region heavy (H) and light (L) chain genes expressed by the variant hybridoma were amplified by polymerase chain reaction, cloned, sequenced, and compared with those of the KIM4.6 parent and other DNA‐binding and non–DNA‐binding antibodies.

Results. The VL chain of the variant was identical to that of KIM4.6. In contrast, the VH chain was completely different from the VH chain of the parent but was similar or identical, except in the diversity (D) and joining regions, to the VH chain of the systemic lupus erythematosus (SLE) IgG anti‐DNA antibody T14 and SLE IgM nephritogenic anti‐DNA antibodies NE‐1 and NE‐13.

Conclusion. The expression of the KIM4.6 VL chain is not sufficient for DNA specificity. The VH chain and its D region play a key role in conferring DNA binding of the KIM4.6 anti‐DNA antibody.
Major histocompatibility complex class ii gene associations with anti–u1 small nuclear ribonucleoprotein antibody relationship to immunoreactivity with individual constituent proteins
Authors: Kuwana Masataka , Okano Yutaka , Kaburaki Junichi , Tsuji Kimiyoshi , Inoko Hidetoshi
Published: February 2007

Objective. To better define immunogenetic associations with the anti–U1 ribonucleoprotein (U1 RNP) autoantibody response.

Methods. HLA class II alleles were determined by genotyping in 49 Japanese rheumatic disease patients with anti–U1 RNP antibody and 43 race‐matched healthy controls. Immunoreactivities to U1 RNP constituent proteins (70K, A, B/B′, and C) were detected by immunoblots using purified HeLa cell Sm antigen, and antibody titer was determined by passive hemagglutination assay.

Results. DQB1*0302 was significantly more frequent in anti–U1 RNP–positive patients than in controls (43% versus 14%; odds ratio [OR] = 4.6, corrected P = 0.03). All anti–U1 RNP–positive patients had either a DQB1*0601, *0602, *0301, *0302, or *0303 allele, which share tyrosine at position 30, and the amino acid sequence Thr, Arg, Ala, Glu, Leu, Asp, and Thr at positions 71–77 in the DQB1 ß1 domain. In contrast, one of these alleles was found in 81% of the controls (OR = 24, P = 0.002). In addition, anti–U1 RNP antibody was associated with unique DQB*0302; DRB1*0401 haplotype. Anti‐70K reactivity and antibody titer were positively associated with a basic amino acid residue, arginine or histidine, at position 13 (DR2 or DR4) and were negatively associated with the amino acid sequence Ile, Leu, Glu, and Asp at positions 67–70, which was present in some of the DR5‐, DR6‐, and DR8‐associated alleles, in the DRB1 ß1 domain. Anti‐C reactivity was strongly associated with DR2, particularly with DRB1*1502.

Conclusion. The several shared epitopes located on HLA–DRB1 and DQB1 genes control the anti–U1 RNP autoantibody response.
E‐selectin expression in salivary endothelial cells and sera from patients with systemic sclerosis
Authors: Hebbar Mohamed , Lassalle Philippe , Janin Anne , Vanhée Dominique , Bisiau Sophie , Hatron Pierre‐Yves , Tonnel André‐Bernard , Gosselin Bernard
Published: February 2007

Objective. To assess endothelial cell activation in patients with systemic sclerosis (SSc).

Methods. Concomitant study of salivary gland biopsy tissues and sera for expression of E‐selectin and its potent activator tumor necrosis factor α (TNFα), using immunostaining and enzyme‐linked immunosorbent essay.

Results. E‐selectin was overexpressed in SSc patients, but not in controls. TNFα was detected in mast cells.

Conclusion. Mast cell–derived TNFα may contribute to endothelial cell activation in SSc.
Discoordinate gene expression of aggrecan and type ii collagen in experimental osteoarthritis
Authors: Matyas John R. , Adams Mark E. , Huang Dingqiu , Sandell Linda J.
Published: February 2007

Objective. To quantify the gene expression of aggrecan core protein and type II collagen in an experimental animal model of osteoarthritis (OA).

Methods. Total RNA was extracted from the articular cartilage of unoperated knee joints and from OA joints produced by anterior cruciate ligament transection. The relative amounts of type II collagen and aggrecan core protein messenger RNA (mRNA) were evaluated by Northern blot analysis.

Results. Total RNA was elevated 2.5 times, aggrecan mRNA was elevated 2 times, and type II collagen mRNA was elevated 8 times, in OA knees compared to unoperated controls.

Conclusion. Chondrocytes are activated metabolically in response to joint injury. Discoordinate gene expression of aggrecan and type II collagen is characteristic of early experimental OA, and we speculate that it may contribute to its pathogenesis.
Polymyositis, pulmonary fibrosis, and hepatitis c
Authors: Weidensaul David , Imam Talha , Holyst Margaret‐Mary , King Paul D. , Mcmurray Robert W.
Published: February 2007

Polymyositis has been associated with several viral infections, and a spectrum of immune‐related diseases may occur with hepatitis C virus (HCV) infection. Both polymyositis and HCV infection may be accompanied by interstitial lung disease; however, no association between polymyositis and HCV infection has been reported previously. We report a new association in a patient with HCV infection: anti‐Jo‐1 positive polymyositis and interstitial lung disease.
Apoptosis and functional fas antigen in rheumatoid arthritis synoviocytes
Authors: Nakajima Toshihiro , Aono Hiroyuki , Hasunuma Tomoko , Yamamoto Kazuhiko , Shirai Toshikazu , Hirohata Kazushi , Nishioka Kusuki
Published: February 2007

Objective. To determine whether apoptosis occurs in rheumatoid arthritis (RA) synoviocytes, and if this phenomenon is dependent on the Fas/Apo‐1 pathway.

Methods. Apoptotic change in vivo was examined in RA synovial cells by several standard methods. The ability of cells to undergo Fas‐induced apoptosis was determined in vitro.

Results. Typical apoptotic change was demonstrated in RA synovial cells by each method. Anti‐Fas antibody induced apoptotic synovial cell death in vitro.

Conclusion. This is the first reported study to demonstrate apoptosis in RA synovial cells. The findings indicate that rheumatoid synoviocytes undergo Fas‐mediated apoptosis.
Complement components C1q, C1r/C1s, and C1inh in rheumatoid arthritis
Authors: Breitner Susanne , Störkel Stephan , Reichel Wolfgang , Loos Michael
Published: February 2007

Objective. To analyze the synovial site and the cell types expressing C1q, C1r/C1s, and C1–esterase inhibitor (C1INH) and to characterize newly synthesized C1q in patients with rheumatoid arthritis (RA).

Methods. Tissue and primary cell cultures of synovium from RA patients were analyzed for C1q, C1r/C1s, and C1INH by Northern blotting, in situ hybridization, and pulse‐chase experiments for C1q.

Results. The de novo synthesis of C1q, C1r/C1s, and C1INH in synovium and primary cell cultures was proven by Northern blot and by antigenic and functional analysis. In in situ hybridization experiments, the synovial lining cell layer was identified as the site of C1q, C1r, and C1INH expression. In contrast, immunohistologic analysis showed that C1q, C1s, and C1INH proteins were present in a thin film covering the synovial lining cells. In situ hybridization performed on primary cell cultures provided evidence that only macrophages were able to express C1q, whereas fibroblasts and stellate cells synthesized C1r.

Conclusion. The synovium is important for the synthesis and secretion of C1q and C1r/C1s, as well as the control protein C1INH, which supports the idea of a locally occurring inflammatory process in RA patients.
Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis
Authors: Braun JÜRgen , Bollow Matthias , Neure Lucia , Seipelt Eva , Seyrekbasan Fikret , Herbst Hermann , Eggens Ulrich , Distler Armin , Sieper Jochen
Published: February 2007

Objective. To investigate mechanisms involved in inflammation and new bone formation in the sacroiliac (SI) joints of patients with ankylosing spondylitis (AS).

Patients and methods. Computed tomography–assisted biopsy of the SI joint was performed in 5 patients with AS with a mean disease duration of 4.5 years and radiographic stage 2–3 disease. Immuno‐histologic studies were performed with the alkaline phosphatase–anti–alkaline phosphatase technique, and cytokine messenger RNA (mRNA) was detected by in situ hybridization.

Results. Dense cellular infiltrates with varying amounts of CD3+ cells (mean ± SD 53.3 ± 24.1%), CD4+ cells (29.7 ± 17.6%), CD8+ cells (15.8 ± 11.4%), CD14+ cells (23.6 ± 16.9%), CD45RO+ cells (48.4 ± 23.6%), and CD45RA+ cells (4.5 ± 2.9%) were found in the synovial portion of the SI joints of all 5 patients. In these infiltrates a high amount of tumor necrosis factor α (TNFα) mRNA and, near the site of new bone formation, a lower amount of transforming growth factor β (TGF β) mRNA, were detected, while no message for interleukin‐1 was found in the 3 patients examined by this technique.

Conclusion. The presence of T cells and macrophages was demonstrated in cellular infiltrates in the SI joints of 5 patients with active AS. The finding of abundant TNFα message in these joints could have implications regarding potential immunotherapeutic approaches to this disease. TGFβ might be involved in new bone formation in AS.
Increased proteoglycan synthesis in cartilage in experimental canine osteoarthritis does not reflect a permanent change in chondrocyte phenotype
Authors: Venn G. , Billingham M. E. J. , Hardingham T. E.
Published: February 2007

Objective. To determine whether chondrocytes in early experimental osteoarthritic (OA) cartilage continue to show increased synthesis and turnover of proteoglycans (PGs) during explant culture. A comparison was also made between the responsiveness of experimental OA and control cartilage to interleukin‐1β (IL‐1β) and tumor necrosis factor α (TNFα) after 1 day and 3 days in culture.

Methods. OA was induced in mature animals by sectioning of the anterior cruciate ligament followed by 3 months of normal exercise. PG synthesis in the articular cartilage was determined by measuring 35S‐sulfate incorporation during explant culture over 1–3 days. Inhibition of PG synthesis was also determined with various concentrations of IL‐1β and TNFα after 1 and 3 days in culture. PGs extracted from the articular cartilage over 1–3 days in culture were examined by agarose–polyacrylamide gel electrophoresis.

Results. Up to 24 hours after excision from the joint, PG synthesis was higher in experimental OA cartilage than in control cartilage. It was also less sensitive to inhibition by TNFα. These differences were no longer detected after 48–72 hours in culture. There were no changes in the relative proportions of aggrecan and decorin/biglycan extracted from and synthesized by control and experimental OA cartilage over the 3 days in culture.

Conclusion. Previous results indicated that PG synthesis and turnover in articular cartilage was increased for many months after induction of experimental OA. Our present results show that the enhanced rate of PG synthesis and turnover were evident in freshly explanted tissue, but the differences were lost over 3 days in culture. A decreased responsiveness to TNFα was also lost. The hypermetabolic activity of experimental OA chondrocytes was thus reversible and not a permanent change in chondrocyte phenotype.
Knee osteoarthritis in former runners, soccer players, weight lifters, and shooters
Authors: Kujala Urho M. , Kettunen Jyrki , Paananen Heli , Aalto Teuvo , Battié Michele C. , Impivaara Olli , Videman Tapio , Sarna Seppo
Published: February 2007

Objective. To determine the relationship between different physical loading conditions and findings of knee osteoarthritis (OA).

Methods. We selected 117 male former top‐level athletes (age range 45–68 years) who had participated in sports activities with distinctly different loading conditions: 28 had been long‐distance runners, 31 soccer players, 29 weight lifters, and 29 shooters. Histories of lifetime occupational and athletic knee loading, knee injuries, and knee symptoms were obtained, and subjects were examined clinically and radiographically for knee findings of OA.

Results. The prevalence of tibiofemoral or patellofemoral OA based on radiographic examination was 3% in shooters, 29% in soccer players, 31% in weight lifters, and 14% in runners (P = 0.016 between groups). Soccer players had the highest prevalence of tibiofemoral OA (26%), and weight lifters had the highest prevalence of patellofemoral OA (28%). Subjects with radiographically documented knee OA had more symptoms, clinical findings, and functional limitations than did subjects without knee OA. By stepwise logistic regression analysis, the risk for having knee OA was increased in subjects with previous knee injuries (odds ratio [OR] 4.73), high body mass index at the age of 20 (OR 1.76/unit of increasing body mass index), previous participation in heavy work (OR 1.08/work‐year), kneeling or squatting work (OR 1.10/work‐year), and in subjects participating in soccer (OR 5.21).

Conclusion. Soccer players and weight lifters are at increased risk of developing premature knee OA. The increased risk is explained in part by knee injuries in soccer players and by high body mass in weight lifters.
Hla–dr8 and acute anterior uveitis in ankylosing spondylitis
Authors: Monowarul Islam S. M. , Numaga Jiro , Fujino Yujiro , Masuda Kanjiro , Ohda Hiromi , Hirata Ranko , Maeda Hiroo , Mitsui Hiroshi
Published: February 2007

Objective. To identify possible factors in the development of acute anterior uveitis (AUU) in patients with ankylosing spondylitis (AS).

Methods. We investigated HLA antigens serologically, and HLA–DRB1*08 alleles by polymerase chain reaction–restriction fragment length polymorphism, in 42 Japanese AS patients with and without AAU.

Results. Thirty‐six of the AS patients (85.7%) had HLA–B27. Thirteen (65%) of the 20 patients with AAU had HLA–DR8, whereas only 1 (4.5%) of the 22 patients without AAU had DR8. The difference was statistically significant (Pcorr < 0.001).

Conclusion. Our data suggest that HLA–B27 is strongly associated with AS in Japanese patients and that HLA–DR8 is important for the development of AAU in Japanese patients with AS.
The prevalence and incidence of systemic lupus erythematosus in Birmingham, England
Authors: Johnson Angela E. , Gordon Caroline , Palmer Robert G. , Bacon Paul A.
Published: February 2007

Objective. To establish the point prevalence of systemic lupus erythematosus (SLE) on January 1, 1992, and the incidence of SLE during 1991, in Birmingham, England, a large city with a broad ethnic mix.

Methods. Six sources were used to ascertain patients with diagnosed SLE, including notification by attending and primary care physicians, the lupus patient support group, and hospital inpatient and laboratory data.

Results. There were 242 SLE patients (227 females, 15 males) identified: prevalence rate 27.7/100,000 (95% confidence interval 24.2–31.2/100,000) in the population and 206.0/100,000 in Afro‐Caribbean females. No significant differences in female ethnic prevalence rates by place of birth were observed. Thirty‐three patients developed SLE in 1991: incidence rate 3.8/ 100,000/year (95% confidence interval 2.5–5.1/100,000/year).

Conclusion. This study illustrates dramatic differences in incidence and prevalence rates in the UK, depending on ethnic group and irrespective of place of birth.
The arthritis knowledge questionnaire
Authors: Edworthy Steven M. , Devins Gerald M. , Watson Margaret M.
Published: February 2007

Objective. To develop a questionnaire for measuring patients' knowledge about arthritis and its self‐management.

Methods. An initial item pool of 175 multiple‐choice questions was developed, based on the Stanford Arthritis Self‐Management Program and on basic medical knowledge about arthritis and its management. A rheumatologist, psychologist, physiotherapist, and several lay individuals assessed the questions for content validity, breadth of coverage, and face validity. Patients assessed the questions for comprehensibility. Four subject groups with varying knowledge levels were recruited to answer the entire set of questions. Item analysis was undertaken to develop parallel forms of subtests so that repeated assessments could be undertaken.

Results. The final instrument, the Arthritis Knowledge Questionnaire, consists of 2 tests, each comprising 3 subtests: self‐management (15 items), arthritis in general (15 items), and rheumatoid arthritis (11 items).

Conclusion. We present psychometric evidence that these parallel forms provide highly reliable and valid estimates of knowledge concerning arthritis and arthritis self‐management.
An analysis of forty‐two wegener's granulomatosis patients treated with methotrexate and prednisone
Authors: Sneller Michael C. , Hoffman Gary S. , Talar‐Williams Cheryl , Kerr Gail S. , Hallahan Claire W. , Fauci Anthony S.
Published: February 2007

Objective. To determine the efficacy of low‐dose methotrexate (MTX) plus prednisone in the treatment of Wegener's granulomatosis (WG).

Methods. An open‐label study of weekly low‐dose MTX plus prednisone for the treatment of WG was performed. Forty‐two patients who did not have immediately life‐threatening disease were enrolled into the study. Outcome was determined by clinical characteristics and pathologic, laboratory, and radiographic findings.

Results. Weekly administration of MTX and prednisone resulted in remission of disease in 30 of the 42 patients (71%). The median time to remission was 4.2 months. The estimated median time to relapse for all patients in whom remission was achieved was 29 months. Eight patients who had relapses were treated with a second course of MTX plus prednisone, and a second remission was induced in 6 of the 8 (75%).

Conclusion. Weekly low‐dose MTX was shown in this study to be an acceptable alternative form of therapy for selected patients with WG who do not have immediately life‐threatening disease or who have developed serious cyclophosphamide‐associated toxicity.
Complications resulting from the use of chinese herbal medications containing undeclared prescription drugs
Authors: Gertner Elie , Marshall Peter S. , Filandrinos Dean , Potek Arnold S. , Smith Theresa M.
Published: February 2007

Objective. Many patients with chronic disease use alternative therapies. Our objective was to investigate complications resulting from the use of Chinese herbal medications containing undeclared prescription drugs, and to analyze these pills.

Methods. Medical records of 5 patients with complications were reviewed. Pills from symptomatic and asymptomatic individuals were analyzed for possible content of undeclared prescription drugs.

Results. All pills analyzed contained mefenamic acid and diazepam. Complications related to the presence of these substances included, among others, massive gastrointestinal bleeding.

Conclusion. Chinese herbal medications may contain undeclared prescription drugs including nonsteroidal antiinflammatory drugs and benzodiazepines.
Antineutrophil cytoplasmic antibodies in systemic lupus erythematosus
Authors: Schnabel Armin , Csernok Elena , Isenberg David A. , Mrowka Christian , Gross Wolfgang L.
Published: February 2007

Objective. To examine the prevalence, subspecificities, and clinical associations of antineutrophil cytoplasmic antibodies (ANCA) in patients with systemic lupus erythematosus (SLE).

Methods. One hundred fifty‐seven sera from 120 patients with SLE were examined for classic (c) and perinuclear (p) pattern ANCA by indirect immunofluorescence. Antibody subspecificities were determined by enzyme‐linked immunosorbent assay (ELISA). Serologic results were correlated with clinical manifestations as categorized by the BILAG (British Isles Lupus Assessment Group) index.

Results. ANCA were found in 40 of the 157 sera (25%). Only a pANCA, not a cANCA, pattern of fluorescence was seen. By ELISA testing, 16 sera reacted to lactoferrin, 8 to elastase, and 4 to lysozyme. There was no reactivity to proteinase 3 (PR3) or myeloperoxidase (MPO). No correlation of pANCA, or any of the ANCA subspecificities, with organ system involvement, as categorized by the BILAG index, was found. Notably, there was no correlation of ANCA results with lupus vasculitis.

Conclusion. The absence of cANCA, anti‐PR3, and anti‐MPO shows that with appropriate assay conditions, ANCA testing assists in the differentiation between SLE and the ANCA‐associated vasculitides. The lack of a correlation between pANCA or any ANCA subspecificity and clinical manifestations suggests that ANCA do not identify particular clinical subsets among SLE patients, including those with lupus vasculitis.
Absence of parvovirus b19 infection in chronic fatigue syndrome
Authors: Ilaria Robert L. , Komaroff Anthony L. , Fagioli Laura R. , Moloney William C. , True Cheryl A. , Naides Stanley J.
Published: February 2007

Objective. To evaluate the presence of infection with parvovirus B19 in patients with chronic fatigue syndrome (CFS) who also had rheumatologic symptoms and mild hematologic abnormalities.

Methods. Seven patients meeting the Centers for Disease Control and Prevention working case definition for CFS who also had mild leukopenia, thrombocytopenia, or anemia were studied. Bone marrow was aspirated from each patient, and examined for morphologic abnormalities, including features seen in marrow infections with parvovirus B19, as well as for parvoviral DNA, using polymerase chain reaction (PCR) amplification. Serum obtained at the time of marrow aspiration was also evaluated for parvoviral DNA, using the PCR method, and was examined for the presence of IgM and IgG antibodies to the virus.

Results. No evidence of marrow involvement with parvovirus B19 was found in any patient. One patient had antibody evidence of a transient parvoviral infection, during which time an underlying thrombocytopenia worsened.

Conclusion. Despite examining a selected group of patients thought most likely to have parvoviral infection, based on clinical and hematologic measures, no evidence of clinically important parvoviral infection was noted. Thus, it seems unlikely that parvovirus B19 plays a role in CFS, even though it has been associated with fibromyalgia, a clinically similar syndrome.
Dysregulation of the in vivo production of interleukin‐1 receptor antagonist in patients with rheumatoid arthritis pathogenetic implications
Authors: Chikanza Ian C. , Roux‐Lombard Pascal , Dayer Jean‐Michel , Panayi Gabriel S.
Published: February 2007

Objective. Patients with rheumatoid arthritis (RA) have defective hypothalamic responses to inflammation, possibly because of excessive production of cytokine inhibitor, which could blunt the effects of cytokines on the hypothalamus, or because of an imbalance between interleukin‐1β (IL‐1β) and interleukin‐1 receptor antagonist (IL‐1Ra), which could create a mainly proinflammatory state. The present study was undertaken to investigate these possibilities.

Methods. The in vivo kinetics of IL‐1β and IL‐1Ra secretion were studied in patients with RA, osteoarthritis (OA), and chronic osteomyelitis (OM), and in normal controls before and after surgery.

Results. The 24‐hour levels of IL‐1Ra were significantly increased in RA (P < 0.001), but there was no diurnal variation in any group. Preoperative levels of IL‐1Ra were higher in RA and OA sera (P = 0.001). After surgery, IL‐1Ra behaved like an acute‐phase reactant protein in all subjects. IL‐1β was 10–20 times higher in RA than in OM and OA patients at baseline, but the percentage increase in all groups postoperatively was the same. RA patients had an IL‐1Ra:IL‐1β ratio of 26.2 ± 3.7 (mean ± SEM) at baseline (OM patients 89.2 ± 5.8 and OA patients 1,310 ± 363); this increased to 66.5 ± 19.8 after surgery (OM patients 120 ± 6.7 and OA patients 325.8 ± 106).

Conclusion. RA patients have a dysregulation of IL‐1Ra production, and it seems unlikely that the defective hypothalamic response seen in RA is due to a functional deficit of IL‐1β.
Cd28 expression on t cell subsets in vivo and cd28‐mediated t cell response in vitro in patients with rheumatoid arthritis
Authors: Sfikakis Peter P. , Zografou Amalia , Viglis Vassilis , Iniotaki‐Theodoraki Aliki , Piskontaki Ifigenia , Tsokos George C. , Sfikakis Paul , Choremi‐Papadopoulou Helen
Published: February 2007

Objective. In view of the critical importance of the CD28–CD80 (B7/BB1) costimulatory pathway in antigen‐specific T cell activation and clonal expansion, we examined CD28 surface molecule expression in vivo, and T cell receptor/CD3‐mediated and B7/BB1‐costimulated T cell proliferation in vitro, in rheumatoid arthritis (RA).

Methods. Two‐color immunofluorescence analyses of peripheral blood and synovial fluid–derived T cells, as well as 3H‐thymidine incorporation assays, were performed.

Results. In the peripheral blood of 31 patients with active, untreated RA, a mean of 91% (range 48–100%) of CD4+ and 46% (range 13–82%) of CD8+ T cell subsets were CD28+, which was not significantly lower than normal. Although an overall decrease in the number of T cells was not observed, the numbers of CD28+CD8+ T cells were significantly lower in RA patients (mean 233/μl, versus 292/μl in controls), and this decrease was more pronounced in patients with severe disease (mean 172/μl). CD28 expression on peripheral CD8+ T cells in RA patients, but not in healthy individuals, correlated inversely with T cell activation as assessed by HLA–DR antigen expression. In contrast to the peripheral blood, RA synovial fluid T cells were almost exclusively CD28+, suggesting that migration of CD28+CD8+ T cells to active sites of inflammation may occur. In vitro proliferative responses of peripheral blood T cells to B7/BB1 costimulation in the presence of mitogenic doses of anti‐CD3 monoclonal antibody were identical in patients with RA and healthy individuals.

Conclusion. Functionally intact CD28+ T cells may contribute to the abnormal immunoregulation and joint inflammation in RA.
Transforming growth factor β1, a major stimulator of hyaluronan synthesis in human synovial lining cells
Authors: Haubeck Hans‐Dieter , Kock RÜDiger , Fischer Dagmar‐Christiane , Leur Eddy Van De , Hoffmeister Karin , Greiling Helmut
Published: February 2007

Objective: To investigate the role of cytokines and growth factors in the regulation of hyaluronan synthesis in human synovial lining cells.

Methods. Synovial lining cells were obtained from human knee joints, isolated by the explant method, and characterized by immunocytochemistry using monoclonal antibodies against monocyte/macrophage markers as well as antibodies against hyaluronan synthase. After stimulation by cytokines and growth factors, hyaluronan was measured by radiometric assay. The molecular weight distribution of the hyaluronan synthesized was determined by high‐performance gelpermeation liquid chromatography. To test the effect of oxygen‐derived free radicals, the concentration and molecular weight distribution of hyaluronan were determined in the presence and absence of catalase and superoxide dismutase.

Results. Hyaluronan synthesis was stimulated in synovial lining cells by transforming growth factor β1 (TGFβ1), interleukin‐1β (IL‐1β), and to a lesser extent by tumor necrosis factor α (TNFα). Analysis of the molecular weight distribution of hyaluronan after stimulation of synovial lining cells with TGFβ1, IL‐1β, and TNFα indicated that hyaluronan is synthesized in a high molecular weight form and might be degraded in the course of inflammatory processes by oxygen‐derived free radicals.

Conclusion. Our findings suggest that TGFβ1 is a major stimulator of hyaluronan synthesis in human synovial lining cells and might be involved in the pathogenic mechanisms of joint swelling in inflammatory and degenerative joint diseases.
Eda‐containing fibronectin is synthesized from rheumatoid synovial fibroblast‐like cells
Authors: Hino Kazuo , Shiozawa Shunichi , Kuroki Yasuo , Ishikawa Hitoshi , Shiozawa Kazuko , Sekiguchi Kiyotoshi , Hirano Hisanobu , Sakashita Eiji , Miyashita Keiichi , Chihara Kazuo
Published: February 2007

Objective. To identify the cells that synthesize EDA‐containing fibronectin (FN) and examine the role of EDA+ FN in the pathogenesis of rheumatoid joint lesions.

Methods. Localization of EDA+ FN and c‐Fos protein in rheumatoid joints was studied immunohistochemically by utilizing antibodies for EDA+ FN and c‐Fos. Expression of EDA+ FN was studied by immunoelectron microscopy and in situ hybridization. The amount of EDA+ FN was measured by enzymelinked immunosorbent assay.

Results. EDA+ FN was specifically localized in the synovial lining layer of synovium with active rheumatoid arthritis (RA) (n = 17), but not in that with osteoarthritis (n = 4) or with inactive fibrous RA (n = 2). EDA+ FN messenger RNA was localized in the synovial lining layer. EDA+ FN was immunoelectron microscopically localized in the synovial lining fibroblast‐like (type B) cells. EDA+ FN was also detected at the cartilage–pannus junction and on the surface of RA cartilage. Double staining showed that EDA+ FN colocalized with c‐Fos protein in the rheumatoid synovial lining layer. Quantification of EDA+ FN showed that it was highly concentrated in rheumatoid synovial fluids.

Conclusion. EDA+ FN is synthesized by the synovial lining fibroblast‐like (type B) cells in situ in rheumatoid synovium, and appears to be expressed in association with activated or transformed states of synovium.
Identification of human t cell leukemia/lymphoma virus type i antibodies, dna, and protein in patients with polymyositis
Authors: Sherman Michael P. , Amin Rajnikant M. , Rodgers‐Johnson Pamela E. B. , Morgan Owen S. C. , Char Gurendra , Mora Carlos A. , Iannone Robert , Collins George H. , Papsidero Lawrence , Gibbs Clarence J. , Poiesz Bernard J.
Published: February 2007

Objective. To investigate a possible association between human T cell leukemia/lymphoma virus type I (HTLV‐I) and polymyositis (PM).

Methods. Sera and muscle biopsy samples from 9 Jamaican PM patients were compared with specimens from American HTLV‐I–positive PM patients and normal controls. Sera were evaluated for HTLV antibodies by enzyme‐linked immunosorbent assay and Western blot. The biopsy samples were analyzed for HTLV‐I/II DNA by polymerase chain reaction and were also immunohistochemically stained for HTLV gp46 envelope protein.

Results. Seven of the 8 Jamaican PM patients from whom sera were available were HTLV‐I seropositive. The muscle biopsies of all 9 Jamaican patients demonstrated severe lymphocytic infiltration, cellular degeneration, myofiber atrophy, and fibrosis. Each muscle biopsy specimen contained HTLV‐I DNA. Two of 6 samples demonstrated intense staining for HTLV‐I gp46 in many of the invading mononuclear cells and weak staining for HTLV‐I gp46 in many of the invading mononuclear cells and weak staining in the adjacent myocytes. Two other specimens were weakly positive for gp46 in rare mononuclear cells. All control specimens were negative for the presence of HTLV‐I DNA and protein.

Conclusion. HTLV‐I is associated with an inflammatory muscle disease characterized by direct invasion of the affected muscle by HTLV‐I–infected mononuclear cells.
Increased levels of substance p and calcitonin gene‐related peptide in rat adjuvant arthritis: combined immunohistochemical and radioimmunoassay analysis
Authors: Ahmed Mahmood , Bjurhol Andres , Schultzberg Marianne , Theodorsson Elvar , Kreicbergs Andris
Published: February 2007

Objective. To analyze the occurrence of substance P (SP) and calcitonin gene–related peptide (CGRP) in ankle joints and corresponding dorsal root ganglia (L2–L6) of rats with adjuvant arthritis.

Methods. Arthritis was induced by inoculation with heat‐killed mycobacteria. The morphologic distribution of SP and CGRP was assessed by immunohistochemical analysis. Tissue concentrations of the neuropeptides were determined by radioimmunoassay.

Results. Neuronal CGRP‐like immunoreactivity was clearly increased in the synovium and the dorsal root ganglia, whereas the increase in SP‐positive structures was less pronounced. The tissue concentrations of SP and CGRP were significantly increased both in ankle joints and in dorsal root ganglia.

Conclusion. Levels of sensory neuropeptides are increased under conditions of joint inflammation.
A fatal pulmonary complication of lupus in pregnancy
Authors: Rubin Laurence A. , Geran Amir , Rose Toby H. , Cohen Howard
Published: February 2007

Pulmonary vasculitis is an uncommon complication of systemic lupus erythematosus (SLE), and has not been previously documented in pregnancy. This case report describes the rapidly fatal course of a pregnant SLE patient, whose terminal illness was manifested by severe pulmonary hypertension and unexpected autopsy findings of medium and large vessel vasculitis. The relationship of these unusual manifestations to other clinical and serologic features of SLE, as well as novel therapeutic options, are discussed.
Expression of e‐selectin messenger RNA and protein in rheumatoid arthritis
Authors: Kriegsmann Jörg , Keyszer Gernot M. , Geiler Thomas , Lagoo Anand S. , Lagoo‐Deenadayalan Sandhya , Gay Renate E. , Gay Steffen
Published: February 2007

Objective. To examine the de novo synthesis and cellular distribution of the E‐selectin adhesion molecule in synovial tissues obtained from patients with rheumatoid arthritis (RA).

Methods. Immunohistochemistry techniques combined with in situ hybridization were used to examine RA synovium.

Results. There were numerous endothelial cells positive for E‐selectin and E‐selectin messenger RNA in the RA synovial membranes. Moreover, E‐selectin expression appeared to correlate with inflammatory activity.

Conclusion. The strong vascular expression of E‐selectin indicates an activation of endothelial cells in the recruitment of cells associated with the chronic inflammation of RA.
Correlation between gold‐induced enterocolitis and the presence of the HLA‐DRB 1*0404 allele
Authors: Evron Ella , Brautbar Chaim , Becker Stuart , Fenakel Gavriel , Abend Yitzhak , Sthoeger Zev , Cohen Patrizia , Geltner David
Published: February 2007

Objective. In recent years we have treated 4 rheumatoid arthritis (RA) patients who developed goldinduced enterocolitis, a well‐recognized, although rare, complication of chrysotherapy. The aim of the present study was to seek any genetic predisposition for this complication.

Methods. HLA DNA typing was done on fresh white blood cells from the 4 patients.

Results. Three of the 4 patients (75%) exhibited the DRB 1*0404 allele, whereas the prevalence of this allele among the Ashkenazi Jewish population of RA patients without colitis was 9.2% and 10.2% in 2 different studies.

Conclusion. The results indicate that the DRB 1*0404 may be associated with risk for the development of gold‐induced enterocolitis in this population and suggest that HLA DNA typing should be considered in Jews who may be undergoing chrysotherapy.
Serum hyaluronic acid level as a predictor of disease progression in osteoarthritis of the knee
Authors: Sharif Mohammed , George Emmanuel , Shepstone Lee , Knudson Warren , Thonar EUGENE J.‐M. A. , Cushnaghan Janet , Dieppe Paul
Published: February 2007

Objective. To investigate the prognostic value of serum hyaluronic acid (HA) and keratan sulfate (KS) levels in relation to tibiofemoral osteoarthritis (OA) of the knee.

Methods. Clinical and demographic data were collected on 94 patients. Radiographs were obtained at study entry and at 5‐year followup. Disease progression was defined as 2 mm of joint space narrowing of any tibiofemoral compartment, and/or knee joint surgery during the study period. Serum HA and KS were measured and levels were correlated with entry data and disease progression.

Results. At entry, HA levels were significantly related to disease duration (P = 0.036), minimum joint space (P = 0.049), and previous surgery (P = 0.001). After these variables were taken into account, patients whose disease had progressed were shown to have had significantly higher levels of HA at baseline compared with those whose disease had not progressed (P = 0.019). However, there were no significant differences in levels of serum KS between those with and those without disease progression, at entry (P = 0.779) or at subsequent visits.

Conclusion. These results suggest that serum HA levels predict disease outcome in OA of the knee and confirm that a single measurement of the serum level of KS is not useful as a prognostic marker in OA.
Finger tendon involvement in rheumatoid arthritis
Authors: Grassi Walter , Tittarelli Egidio , Blasetti Patrizia , Pirani Osvaldo , Cervini Claudio
Published: February 2007

Objective. To characterize finger tendon involvement in patients with rheumatoid arthritis (RA).

Methods. The finger tendons of 20 RA patients were studied by ultrasonography using a high‐frequency (13‐MHz) transducer.

Results. Eighteen patients (90%) showed finger tendon abnormalities: widening of the flexor tendon sheath (80%), loss of the normal fibrillar echotexture (60%), irregularity of the extensor (30%) and flexor (50%) tendon margins, tendon tear (10%), synovial cyst (20%).

Conclusion. High‐frequency sonography is helpful in assessing even minimal finger tendon lesions in RA patients.
A self‐administered rheumatoid arthritis disease activity index (RADAI) for epidemiologic research
Authors: Stucki Gerold , Liang Matthew H. , Stucki Susanne , Brühlmann Pius , Michel Beat A.
Published: February 2007

Objective. To examine the psychometric properties and construct validity of a self‐administered Rheumatoid Arthritis Disease Activity Index (RADAI).

Methods. Five items of the Rapid Assessment of Disease Activity in Rheumatology (RADAR) questionnaire were aggregated into the RADAI and assessed for their factor loading, internal consistency, and construct validity.

Results. In 55 patients with RA, the RADAI had a high internal consistency (Cronbach's alpha = 0.91) and correlated with physician's assessment of disease activity (r = 0.54, P < 0.01), the swollen joint count (r = 0.54, P < 0.01), and the C‐reactive protein value (r = 0.43, P < 0.01).

Conclusion. The RADAI is a highly reliable and valid self‐administered measure of disease activity for clinical, health services, and epidemiologic research. Its sensitivity to change in longitudinal studies needs further study.
Cardiovascular fitness and health in patients with end‐stage osteoarthritis
Authors: Philbin Edward F. , Groff Gerald D. , Ries Michael D. , Miller Thomas E.
Published: February 2007

Objective. To evaluate the cardiovascular fitness of a group of patients with severe osteoarthritis (OA).

Methods. Thirty‐seven patients with end‐stage OA were evaluated just before hip or knee replacement surgery. Severity of arthritis was evaluated using standardized techniques. Patients and age‐ and sex‐matched controls underwent a single, maximal, symptomlimited, cardiopulmonary exercise test using arm or leg ergometry and a metabolic cart to measure expired respiratory gases.

Results. Severe musculoskeletal disability and deformity was confirmed in the OA patient group. During exercise testing, OA patients were able to perform physiologically maximal cardiopulmonary exercise. Arthritis patients were noted to be severely deconditioned, with reduced peak oxygen consumption (OA hips mean ± SD 14.9 ± 4.2 versus control hips 19.0 ± 4.6, P < 0.0001; OA knees 12.8 ± 3.7 versus control knees 17.6 ± 5.2 ml/kg/minute, P < 0.0005). A trend for more frequent manifestations of coronary heart disease in OA patients than in controls (27% versus 13%; P > 0.05) was also noted.

Conclusion. Patients with end‐stage lower extremity OA are severely deconditioned. This may place them at incremental risk for the development of coronary heart disease.
Osteoporosis in rheumatoid arthritis
Authors: Sambrook Philip N. , Spector Timothy D. , Seeman Ego , Bellamy Nicholas , Buchanan Russell R. C. , Duffy David L. , Martin Nicholas G. , Prince Richard , Owen Evan , Silman Alan J. , Eisman John A.
Published: February 2007

Objective. To quantify the magnitude and distribution of osteoporosis in rheumatoid arthritis (RA).

Methods. Bone mineral density (BMD) was measured by dual x‐ray absorptiometry, in a monozygotic co‐twin control study.

Results. BMD was reduced at most skeletal sites in the twin with RA compared with the co‐twin (lumbar spine 4.6%, femoral neck 9.7%, total body 5.7%). Differences in lean soft tissue (5.6% for total body) correlated with differences in BMD between twins at multiple sites.

Conclusion. Osteoporosis in RA is generalized and may be related to loss of mobility or muscle mass associated with the disease.
Spin‐spin relaxation of brain tissues in systemic lupus erythematosus
Authors: Sibbitt Wilmer L. , Brooks William M. , Haseler Luke J. , Griffey Richard H. , Frank Loren M. , Hart Blaine L. , Sibbitt Randy R.
Published: February 2007

Objective. To correlate the spin‐spin relaxation time (T2) of brain tissue in neuropsychiatric systemic lupus erythematosus (NPSLE) with the patient's clinical condition.

Methods. T2 values were determined in 54 SLE patients and 45 non‐SLE controls at 1.5 Tesla, using intensity from multi‐echo magnetic resonance (MR) images fitted to an exponential decay curve with rateconstant T2.

Results. The T2 of white matter was increased in SLE patients compared with controls (P = 0.01) and was increased in those patients who had previously experienced major NPSLE. Patients with acute diffuse neurologic manifestations (seizures, psychosis, coma) demonstrated a longer T2 of the gray matter (mean ± SD 92.75 ± 6.35 ms, n = 10) than did other SLE patients (mean ± SD 79.61 ± 5.04 ms, n = 44) (P = 0.02 by t‐test), which suggests acute cerebral edema. The mean T2 values of reversible and nonreversible focal lesions were significantly different (P < 0.02), indicating different microenvironments and micropathology.

Conclusion. Quantitative T2 measurement extends the utility and sensitivity of conventional MR imaging for evaluating NPSLE.
Use of magnetic resonance imaging and positron emission tomography in the assessment of synovial volume and glucose metabolism in patients with rheumatoid arthritis
Authors: Polisson Richard P. , Schoenberg Oded I. , Fischman Alan , Rubin Robert , Simon Lee S. , Rosenthal Daniel , Palmer William E.
Published: February 2007

Objective. To measure the anatomic and physiologic changes in the synovium of patients with active rheumatoid arthritis (RA) before and after the initiation of treatment with low‐dose systemic glucocorticoids and methotrexate (MTX).

Methods. Two patients with RA with active synovitis involving the carpus were evaluated by imaging parameters at baseline and again after 14 weeks (of treatment with low‐dose prednisone and MTX). Standard clinical parameters, laboratory measurements, and contrast‐enhanced magnetic resonance imaging (MRI) (synovial volume estimate) and positron emission tomography (PET) with 18F‐fluoro‐2‐deoxyglucose (18‐FDG) (synovial metabolism estimate) were performed.

Results. Compared with baseline, standard clinical parameters (i.e., joint count, joint index, morning stiffness, global assessments of arthritis activity, and erythrocyte sedimentation rate) improved dramatically in both patients after treatment with low‐dose prednisone and MTX. In concert with this trend, the synovial volume of the affected wrist was reduced by 60%, and 76% and the metabolism of 18‐FDG was reduced by 66% and 69% in the 2 patients.

Conclusion. These preliminary observations indicate that a volumetric estimate of inflamed synovium (using contrast‐enhanced MRI) and quantification of synovial deoxyglucose metabolism (using PET) are technically feasible and, in the 2 reported cases, correlate well with standard outcome measures. These imaging modalities may provide new objective parameters to determine RA disease activity and effectiveness of antirheumatic medications; however, the potential clinical utility of these measures remains to be defined.