bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of the Alternative Complement Pathway Accompanies Disease Flares in Systemic Lupus Erythematosus During Pregnancy
Authors: Buyon Jill P. , Tamerius John , Ordorica Steve , Young Bruce , Abramson Steven B. 
Published: February 2007

AbstractObjective. To assess the activity of systemic lupus erythematosus (SLE) during pregnancy and to distinguish it from preeclampsia.Methods. We prospectively measured the complement activation products Ba, Bb, SC5b—9, and C4d, as well as the conventional complement determinants C3, C4, and CH50, during pregnancy in 14 patients with SLE and 10 women with preeclampsia.Results. Four of the 14 SLE patients were considered to have disease flares, 3 occurring in the second trimester and 1 postpartum. In these patients, significant abnormalities of Ba, Bb, SC5b—9, and CH50 were noted. In contrast, measures of C4d did not distinguish between pregnant patients who had flares and those whose SLE remained stable. Although decreased values of C3 were rarely seen in the patients with stable disease, normal values of C3 during lupus pregnancy were not reliably associated with stable disease. Three of 10 non‐SLE patients with preeclampsia had elevated levels of Ba; however, in each case, the CH50 level was close to or within the normal range. This was in sharp contrast to the findings observed in the 4 patients with active SLE, in whom high levels of plasma Ba were always associated with low CH50 values. Moreover, the ratio of CH50 to Ba was significantly lower in the patients with lupus flares than in the non‐SLE patients with preeclampsia.Conclusion. While a decline in the CH50 level alone could otherwise be attributed to decreased synthesis of complement components, these data demonstrate that ongoing activation of the alternative complement pathway can accompany disease flares in pregnant women with SLE.
Expression of Cell‐Adhesion Molecules in the Salivary Gland Microenvironment of Sjögren's Syndrome
Authors: Clair E. William S.T. , Angellilo John C. , Singer Kay H. 
Published: February 2007

AbstractObjective. The potential role of cell adhesion molecules in the pathogenesis of Sjögren's syndrome (SS) was assessed by examining their expression in salivary gland (SGL) tissue.Methods. Intercellular adhesion molecule type 1 (ICAM‐1), lymphocyte function‐associated antigen type 1 (LFA‐1), LFA‐3, CD2, and CD44 expression were determined using indirect immunofluorescence techniques.Results. In inflamed labial SGL tissue, ICAM‐1 expression was evident on infiltrating LFA‐1+/CD2+/LFA‐3+ mononuclear cells, and to a limited extent on SGL acinar epithelial cells adjacent to sites of intense inflammation.Conclusion. In SS, the SGL microenvironment is characterized by only a modest up‐regulation of ICAM‐1 expression on epithelial cells, despite the presence of T cells bearing an activated phenotype.
Antibodies to Carbonic Anhydrase in Systemic Lupus Erythematosus and Other Rheumatic Diseases
Authors: Itoh Yasuhiko , Reichlin Morris 
Published: February 2007

AbstractObjective. Autoantibodies to CA were demonstrated in the sera of patients with systemic lupus erythematosus (SLE) and some other rheumatic diseases. This study was undertaken to define the isoform and species specificity of these reactions, as well as to develop a method for detecting immune complexes.Methods. Antibodies to CA were sought by enzyme‐linked immunosorbent assay (ELISA) and by Western immunoblotting.Results. An increased prevalence of CA autoantibodies was detected, by both methods, in patients with SLE, scleroderma, and polymyositis, compared with controls. In SLE patients, CA autoantibodies occurred preferentially in those with anti—U1 RNP or anti‐U1 RNP and Ro/SS‐A. Some sera reacted with only the CA 1 or CA II isoform, while ˜50% of sera that were CA positive reacted with both isoforms. The autoantibodies reacted preferentially with the human enzymes, rather than the bovine CA, both on Western blot and by ELISA. Selected IgG F(ab')2 fragments from anti‐CA—containing sera specifically inhibited the enzyme activity of CA, and the CA inhibitor acetazolamide partially inhibited the binding of anti‐CA to CA. Thus, at least a part of autoanti‐CA is directed toward the active site of CA. Finally, CA molecules were detected as immune complexes in sera from selected anti‐CA‐positive patients.Conclusion. Autoantibodies to CA represent a previously unrecognized autoantibody to an abundant intracellular protein of the human erythrocyte.
Molecular Genetic Analysis of HLA—DR and HLA—DQ Genes Among Anti—U1‐70‐kd Autoantibody Positive Connective Tissue Disease Patients
Authors: Kaneoka Hidetoshi , Hsu Kou‐Ching , Takeda Yoshihiko , Sharp Gordon C. , Hoffman Robert W. 
Published: February 2007

AbstractObjective. We have recently found that the presence of autoantibodies against the 70‐kd polypeptide of U1 RNP (U1‐70‐kd) is associated with HLA—DR4 and DR2. To further characterize this association, we performed a molecular genetic analysis of HLA—DR and DQ genes among patients with autoantibodies against U1‐70‐kd.Methods. The polymerase chain reaction (PCR), sequence‐specific oligonucleotide hybridization, and solid‐phase direct DNA sequencing of PCR‐amplified DNA were utilized to analyze HLA—DRB1, DRB5, DQA1, and DQB1 genes.Results. A comprehensive analysis of HLA—DRB1, DRB5, DQA1, and DQB1 from 27 patients and controls identified shared amino acids FDYFYQA (Phe, Asp, Tyr, Phe, Tyr, Gln, Ala) at positions 26, 28, 30—32, 70, and 73 of HLA—DRB1 on disease‐associated haplotypes.Conclusion. A common cluster of shared amino acids, or a shared epitope, identified within HLA—DRB1 among anti—U1—70‐kd autoantibody positive connective tissue disease patients may be important in regulating an autoimmune response to the U1—70‐kd antigen.
Antibiotic Treatment of Venereal Disease and Reiter's Syndrome in a Greenland Population
Authors: Bardin Thomas , Enel Catherine , Cornelis FrançOis , Salski Chris , Jorgensen Christian , Ward Richard , Lathrop G. Mark 
Published: February 2007

AbstractObjective. To assess the effects of antibiotic treatment of urethritis or cervicitis on the incidence of recurrences of articular symptoms in Reiter's syndrome patients.Methods. Retrospective evaluation of the medical charts of 109 patients living in Greenland.Results. Thirty‐seven percent of the episodes of genitourinary tract inflammation that were not treated or were treated with penicillin were followed by arthritis, compared with 10% of those treated with tetracycline or erythromycin.Conclusion. Antibiotics active against Chlamydia trachomatis reduced the risk of postvenereal arthritis in the population studied.
Interactions Between Anticollagen Antibodies and Chondrocytes
Authors: Takagi Toshitaka , Jasin Hugo E. 
Published: February 2007

AbstractObjective. To investigate the interactions between anticollagen antibodies and living chondrocytes.Methods. Mouse monoclonal anti—type II collagen (anti‐CII) antibodies, rabbit anti‐human CII, and rat anti‐CII, anti‐CIV, anti‐CV, anti‐CVI, and anti‐CIX were studied in vitro to determine their ability to bind to the plasma membrane of living bovine chondrocytes.Results. Mouse monoclonal anti‐CII, rabbit anti‐CII, and rat anti‐CII, anti‐CV, anti‐CVI, and anti‐CIX were shown to bind in vitro to the plasma membrane of bovine chondrocytes. Antibody binding was not observed with anti‐CIV, or with chondrocytes previously incubated with bacterial collagenase. A significant increase in chondrocyte caseinase and collagenase secretion was observed following sequential incubation with the monoclonal antibodies and a source of activating cytokines.Conclusion. These results suggest that collagen autoantibodies may exert some of their pathogenic effects on cartilage through interactions with resident chondrocytes, leading to modulation of the rate of secretion of cartilage matrix—degrading enzymes.
A revised estimate of twin concordance in systemic lupus erythematosus
Authors: Deafen Dennis , Escalante Agustin , Weinrib Lisa , Horwitz David , Bachman Barbara , Roy‐Burman Pradip , Walker Ann , Mack Thomas M. 
Published: February 2007

AbstractObjective. Based on a small clinical series and previously published case reports, concordance for systemic lupus erythematosus (SLE) among monozygous (MZ) twins has been reported to be as high as 69%. Using a larger and less biased sample, we provide another estimate of this percentage.Methods. We established a registry of twins with SLE, based upon self‐reports and information provided by the patients' physicians. We used DNA fingerprinting to validate the reported zygosity in a sample of these twins.Results. Of 107 twin pairs meeting the American College of Rheumatology 1982 revised criteria for the diagnosis of SLE, 24% of 45 MZ pairs and 2% of 62 dizygous (DZ) pairs were concordant. The frequency distributions of diagnostic criteria and disease symptoms in the SLE patients were similar to those in other published reports of SLE patients. Zygosity was confirmed by DNA fingerprinting in a subsample of 15 self‐described MZ twins and 7 self‐described DZ twins. AH individuals had correctly predicted their zygosity.Conclusion. MZ concordance for SLE is similar to that for other autoimmune diseases and is much lower than previously believed.
Extracorporeal photochemotherapy for the treatment of systemic lupus erythematosus. A Pilot study
Authors: Knobler Robert M. , Graninger Winfried , Graninger Wolfgang , Lindmaier Andreas , Trautinger Franz , Smolen Joseph S. 
Published: February 2007

AbstractObjective. To investigate the effectiveness and feasibility of extracorporeal photochemotherapy (ECP) in the treatment of an autoimmune disease with known cutaneous photosensitivity.Methods. Ten patients with systemic lupus erythematosus (SLE) were treated with ECP in an open clinical trial. The efficacy of treatment was analyzed by means of established disease activity scores.Results. Eight patients completed the trial. In 7 of the 8, there was a significant response to the treatment, with no or minor side effects. The clinical activity score in the group of 8 patients decreased from a median of 7 (range 4–9) to a median of 1 (range 0–5) (P < 0.05). Laboratory abnormalities did not change significantly, but were mild at the outset.Conclusion. ECP led to clinical improvement of SLE without side effects. The effectiveness of this method should be investigated further in controlled clinical trials.
Basic calcium phosphate crystals stimulate cell proliferation and collagenase message accumulation in cultured adult articular chondrocytes
Authors: Mitchell Peter G. , Struve Janine A. , Mccarthy Geraldine M. , Cheung Herman S. 
Published: February 2007

AbstractObjective. To investigate BCP (basic calcium phosphate) crystal—stimulated mitogenesis and collagenase gene transcription in primary cultures of porcine chondrocytes.Methods. The role of protein kinases in BCP crystal—stimulated DNA synthesis was investigated using thymidine incorporation, kinase inhibitors, and protein kinase C (PKC) assays. Northern blot analysis was used to determine the levels of collagenase c‐fos and c‐jun message.Results. BCP crystals stimulated chondrocyte proliferation in a PKC‐dependent manner. Increased levels of collagenase message were preceded by an increased accumulation of c‐fos, but not c‐jun.Conclusion. BCP crystals could contribute to the abnormal chondrocyte proliferation and collagenase secretion observed in some rheumatic diseases.
Use of short‐term efficacy/toxicity tradeoffs to select second‐line drugs in rheumatoid arthritis. A metaanalysis of published clinical trials
Authors: Felson David T. , Anderson Jennifer J. , Meenan Robert F. 
Published: February 2007

AbstractObjective. Preferred drugs for rheumatoid arthritis (RA) should be those that have maximal efficacy with the least toxicity. We evaluated the efficacy and toxicity tradeoffs for drugs frequently used in the treatment of RA.Methods. We updated 2 metaanalyses of published clinical trials, by adding trials published through 1990 and trials of azathioprine (AZA). We tested 3 different definitions of efficacy, each plotted against 3 different toxicity measures, for antimalarial drugs, methotrexate (MTX), auranofin, injectable gold, D‐penicillamine, sulfasalazine (SSZ), AZA, and placebo. Efficacy measures included composite efficacy (a combination of joint count, grip strength, and erythrocyte sedimentation rate), tender joint count alone, and a measure based on how many patients dropped out due to inefficacy. Toxicity measures were the proportion dropping out due to toxicity, the same dropouts with side effects weighted for severity using a modification of a published toxicity index, and the proportion with severe toxicities (defined as a score of at least 7 of 10 on the toxicity index). The latter were usually organ toxicities (e.g., cytopenias and renal involvement).Results. All 9 efficacy/toxicity tradeoff plots suggested that MTX and antimalarial drugs had the highest efficacy relative to toxicity. MTX scored among the most efficacious of the drugs and, of these, had the least toxicity. Antimalarial drugs, though showing only moderate efficacy, had the lowest toxicity rate of all the drugs. SSZ scored close to MTX but was, in general, slightly more toxic.Conclusion. In the short‐term context of clinical trials, antimalarial drugs and MTX have the best efficacy/toxicity tradeoffs and may, therefore, be the preferred drugs.
Treatment of systemic sclerosis with recombinant interferon‐γ. A phase I/II clinical trial
Authors: Freundlich Bruce , Jimenez Sergio A. , Steen Virginia D. , Medsger Thomas A. , Szkolnicki Michelle , Jaffe Howard S. 
Published: February 2007

AbstractObjective. A phase I/II trial to examine the safety and efficacy of interferon‐γ (IFNγ) therapy for patients with systemic sclerosis (SSc).Methods. An 18‐week open‐label study was performed. Eighteen patients with rapidly progressive SSc were enrolled, 14 of whom completed at least 16 weeks of the study. These 14 patients had a mean age of 40 years and had been diagnosed as having SSc an average of 10.1 months prior to study entry. Recombinant IFNγ was injected intramuscularly 3 times weekly for 18 weeks. Six patients received a 0.1 mg/m2 dose, while 8 patients received a 0.5 mg/2 dose. Patients who completed the 18‐week trial were offered maintenance therapy at a dose of up to 0.5 mg/m2. The effects of IFNγ on skin involvement were assessed by 2 methods: 1) evaluation of skin thickness, by scoring 15 zones according to a 0 (normal skin) to 3 (hidebound skin) scale; and 2) determination of the total body surface area involved, by using 2‐dimensional body diagrams to indicate areas affected, and then having a second, “blinded,” assessor calculate the area score with a planimeter.Results. The mean skin thickness score decreased from a baseline of 25.9 to 19.1 (P < 0.03), and the mean area scores declined from 33.1 to 19.6 (P < 0.02) after 18 weeks of IFNγ treatment. Ten patients had a >25% decrease in area score. Five patients had a ⩾70% decrease in area score, and 3 of them have not experienced disease recurrence for 6 to 17 months after discontinuation of IFNγ. Five patients withdrew before the study ended. Three of these patients developed renal crisis, which may reflect the severity of the SSc in the study group, although an adverse effect of IFNγ in SSc cannot be excluded.Conclusion. IFNγ was associated with a beneficial effect on the skin involvement in most of this series of patients with rapidly progressive SSc. A placebo‐controlled study will be necessary to confirm these results.
Light microscopic characterization of the fibroblast‐like synovial intimal cell (synoviocyte)
Authors: Wilkinson Linda S. , Pitsillides Andrew A. , Worrall Jennifer G. , Edwards Jo C. W. 
Published: February 2007

AbstractObjective. To reassess synovial intimal cell populations by light microscopy.Methods. Non‐inflamed, rheumatoid and osteoarthritic synovia were analyzed as tissue sections and cytospin preparations by a series of combined immunohistochemical and cytochemical staining techniques.Results. Two populations of intimal cells were identified. The first carried macrophage markers. The second showed high uridine diphosphoglucose dehydrogenase (UDPGD) activity, minimal cytoplasmic CD68, absent non‐specific esterase (NSE) activity, and absent leukocyte and endothelial antigens. The majority of these cells showed a high content of prolyl hydroxylase.Conclusion. Combined cytochemical staining for NSE and UDPGD activity allows effective separation of intimal cell populations. We suggest that the cells of high UDPGD activity are the fibroblast‐like or type B synovial intimal cells defined by electron microscopy. High UDPGD activity probably reflects a preferential ability to synthesize glycosaminoglycans, including hyaluronan.
The development of monoclonal antibodies to the human mitochondrial 60‐kd heat‐shock protein, and their use in studying the expression of the protein in rheumatoid arthritis
Authors: Sharif Mohammed , Worrall Jennifer G. , Singh Bhag , Gupta Radhey S. , Lydyard Peter M. , Lambert Claude , McCulloch John , Rook Graham A. 
Published: February 2007

AbstractObjective. To assess the claim that the human 60‐kd heat‐shock protein (HSP) is highly expressed in the joints of patients with rheumatoid arthritis (RA), but is not readily detected in normal tissues.Methods. Monoclonal antibodies were raised against the human 60‐kd mitochondrial heat‐shock protein (P1 protein; hsp60), and their specificity was established. They were then applied to synovial tissue.Results. HSP was expressed similarly in normal, osteoarthritic, and RA synovium. Low levels of hsp60 were detected in synovial fluid by immunoprecipitation.Conclusion. Minor differences in the distribution of hsp60 in synovium from RA joints were attributable to increased cellularity and to the disorganization of the tissue architecture.
Auranofin‐induced vasomotor reaction
Authors: Proudman S. M. , Cleland L. G. 
Published: February 2007

AbstractVasomoto reactions after administraton of gold sodium thiomalate (GST)are well recognized, ut such reacti9os have not bn reported to ccur in assocation woth oral gold treatment. We descrbe a woman with rheumatoid arthritis who exprienced typical nitritoid reactions after treatment with GST, and later, with auranofin.
Rheumatoid synovium is enriched in CD45RBdim mature memory T cells that are potent helpers for B cell differentiation
Authors: Thomas Ranjeny , McIlraith Melissa , Davis Laurie S. , Lipsky Peter E. 
Published: February 2007

AbstractObjective. To delineate the phenotype and function of synovial T cells in rheumatoid arthritis (RA).Methods. T cells from normal subjects or from RA peripheral blood (PB), synovial fluid (SF), or synovial tissue (ST) were analyzed phenotypically and functionally.Results. RA SF and ST T cells were found to be markedly enriched in CD45RAdim, CD45RO+, CD45RBdim mature memory cells, whereas in the PB, CD45RAbright naive T cells were more frequent than CD45RO+ memory T cells, and only a minority were CD45RBdim. SF and ST T cells proliferated less well and produced less interleukin‐2 in response to mitogenic stimuli than did PB T cells. However, synovial T cells effectively promoted the production of Ig from normal B cells. Moreover, PB and synovial T cells differed in their capacity to down‐regulate immunoglobulin production. Anti‐CD3—stimulated PB T cells suppressed Ig production unless their proliferation was prevented with mitomycin C. In contrast, synovial T cells were potent helpers of B cell Ig production regardless of antecedent treatment with mitomycin C. To examine the relationship between the CD45RBdim phenotype and B cell help, CD45RBdim T cells were sorted from PB. As opposed to the findings with synovial T cells, suppression by control PB CD45RBdim T cells was observed, but only when large numbers were employed. B cell Ig production was enhanced after treatment of PB CD45RBdim T cells with mitomycin C. In contrast, healthy control sorted CD45RBbright or sorted CD4+, CD45RO+, CD45RBbright T cells did not support Ig secretion. After treatment with mitomycin C, both of these populations were more effective helpers of Ig production.Conclusion. RA synovium is enriched in differentiated CD45RBdim memory T cells with potent helper activity and diminished capacity to down‐regulate B cells, strongly implying an active role for these cells in the production of Ig in the synovium, and thus in the propagation of disease.
ATP‐induced chondrocalcinosis
Authors: Ryan Lawrence M. , Kurup Indira V. , Derfus Beth A. , Kushnaryov Vladimir M. 
Published: February 2007

AbstractObjective. To determine whether adult articular cartilage mineralizes in the presence of ATP.Methods. Intact adult porcine articular cartilage and monolayers of chondrocytes were cultured in physiologic media containing ATP, and mineralization was measured as retention of 45Ca. Cartilage was analyzed by electron microscopy.Results. Articular cartilage sequestered 45Ca when incubated with 100 γM ATP. Use of the ATP analog α,β‐methylene ATP did not promote mineralization and addition of pyrophosphatase inhibited mineralization, indicating that hydrolysis of ATP to AMP and inorganic pyrophosphate is necessary for the process to occur. Mineral was concentrated in articular cartilage vesicles in the perichondral area.Conclusion. Adult articular cartilage mineralizes in the presence of ATP, in a manner similar to that found with isolated matrix or articular cartilage vesicles. This supports the notion that these structures have a role in chondrocalcinosis.
Independent regulation of plasminogen activator inhibitor 2 and plasminogen activator inhibitor 1 in human synovial fibroblasts
Authors: Hamilton John A. , Cheung Daisy , Filonzi Enrico L. , Piccoli Diana S. , Wojta Johann , Gallichio Marisa , McGrath Katherine , Last Karena 
Published: February 2007

AbstractObjective. To study the plasminogen activator inhibitor(s) (PAI) produced in vitro by human synovial fibroblast‐like cells.Methods. Human synovial cell explant cultures were established using cells from nonrheumatoid donors. PAI‐2 and PAI‐1 antigens were measured by enzyme‐linked immunosorbent assay, and messenger RNA (mRNA) levels were determined by Northern blot.Results. The synovial fibroblasts produced both PAI‐2 and PAI‐1. Interleukin‐1 (IL‐1) increased PAI‐2 but decreased PAI‐1 formation, both at the protein and the mRNA levels. Using cyclooxygenase inhibitors, evidence was obtained that an endogenous cyclooxygenase product(S) in the IL‐1—treated cultures inhibited formation of both PAIs; exogenous prostaglandin E2 (10−7M) reversed the effect of cyclooxygenase inhibition. The glucocorticoid dexamethasone (10−6 to 10−7M) inhibited IL‐1—stimulated PAI‐2 formation but reversed the suppressive effect of IL‐1 on PAI‐1 production.Conclusion. PAI‐2 formation and PAI‐1 formation can be regulated independently in human synoviocytes, illustrating the complexity of the modulation of the net PA activity expressed by these cells.
Local Proliferation of Fibroblast‐Like Synoviocytes Contributes to Synovial Hyperplasia
Authors: Qu Zhenhong , Garcia Cesar Hernandez , O'Rourke Leslie M. , Planck Stephen R. , Kohli Manoj , Rosenbaum James T. 
Published: February 2007

AbstractObjective. To test the hypothesis that local proliferation contributes significantly to the hyperplasia of rheumatoid synovium.Methods. Immunohistologic and chemical staining was used to identify 3 markers of cell proliferation: proliferating cell nuclear antigen, c‐myc proto‐oncogene, and nucleolar organizer regions. Synovium from 21 patients with rheumatoid arthritis, 34 with degenerative joint disease, and 7 with joint trauma was examined.Results. All 3 markers indicated substantial, active proliferation of synovial lining cells in synovium with hyperplasia. Proliferating cells showed type I procollagen immunoreactivity but were negative for CD68, a monocyte/macrophage marker. Proliferation was greater in rheumatoid arthritis than in the other conditions evaluated.Conclusion. In situ proliferation of fibroblast‐like synoviocytes in the synovium lining contributes considerably to the increase in cell numbers in rheumatoid synovium.