bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical, serologic, and immunogenetic studies in childhood‐onset systemic lupus erythematosus
Authors: Barron Karyl S. , Silverman Earl D. , Gonzales Juanita , Reveille John D. 
Published: February 2007

AbstractObjective. To determine the frequency of systemic lupus erythematosus (SLE)—associated clinical manifestations, autoantibodies, and HLA class II alleles in a large cohort of patients with childhood‐onset SLE.Methods. Eighty children with SLE onset before age 18 (27 before age 11) were studied for the frequency of renal, neuropsychiatric, and hematologic complications as well as for anti—native DNA, Ro, La, Sm, and U1 RNP autoantibodies. HLA—DR, DQ, and DP alleles were determined by oligotyping. The results were compared with findings in 213 adults with SLE onset at or after age 18 years.Results. Renal involvement was more frequent in those with childhood‐onset SLE, especially those with onset before age 11 (82%, compared with 53% in adults). Anti—U1 RNP was more common in American blacks with SLE onset before age 18. HLA—DRB1*0301, DQA1*0501, DQB1*0201 was more common in Caucasians and DRB1*1503, DRB5*0101, DQA1*0102, DQB1*0602 in American blacks, regardless of age at SLE onset. Anti‐Sm autoantibodies were most highly associated with HLA—DQA1*0102 and DQB1*0602.Conclusion. While childhood‐onset SLE shares many immunogenetic and serologic similarities to adultonset disease, important clinical differences nevertheless exist in children with this disease.
A peptide derived from an autoantibody can stimulate t cells in the (nzb × nzw)f1 mouse model of systemic lupus erythematosus
Authors: Ebling Fanny M. , Tsao Betty P. , Singh Ram R. , Sercarz Eli , Hahn Bevra H. 
Published: February 2007

AbstractObjective. To assess the ability of peptides derived from anti‐DNA to stimulate syngeneic T lymphocytes and influence lupus in (NZB × NZW)F1 (NZB/W) mice.Methods. We synthesized (by Geysen pin method) overlapping 12‐mer peptides recapitulating the amino acid sequence of the VH region of a nephritogenic monoclonal IgG2a anti‐DNA antibody (A6.1) from an NZB/W mouse. Splenic T cells were cultured with the peptides; multiple experiments assayed 12‐mer and 16‐mer peptides which contained a triple‐base motif (KFKGK). We immunized 20‐week‐old NZB/W mice with the 12‐mer and evaluated them for evidence of nephritis and for quantities of antibodies in plasma and glomeruli.Results. Three clusters of peptides caused proliferation of spleen cells from young, nonimmunized mice. Both the 12‐mer FYNQKEKGKATL and the 16‐mer GDTFYNQKEKGKATLT peptides stimulated purified T cells. The KXKXK motif occurs in 15% of murine IgVH (NBRF protein database), compared with 100% (6 of 6) of NZB/W anti‐DNA monoclonal antibody. Immunization with the 12‐mer peptide increased plasma levels of IgG, anti‐DNA, and immune complexes, and levels of anti‐DNA in glomeruli; nephritis was accelerated.Conclusion. NZB/W anti‐DNA contain peptide sequences in their VH regions that stimulate self—T cells. At least one motif is frequent in NZB/W anti‐DNA. If some activated T cells provide help, this mechanism may contribute to sustained up‐regulation of autoantibodies in murine lupus.
Molecular analysis of rheumatoid factors derived from rheumatoid synovium suggests an antigen‐driven response in inflamed joints
Authors: Ermel Richard W. , Kenny Thomas P. , Chen Pojen P. , Robbins Dick L. 
Published: February 2007

AbstractObjective. Understanding the molecular genetic basis for rheumatoid factor (RF) production is necessary to a better understanding of the etiology and pathogenesis of rheumatoid arthritis (RA). We sought to define the genetic basis of RF in RA.Methods. The heavy and light chain variable region genes encoding 4 human monoclonal RF were cloned and sequenced using the polymerase chain reaction and the dideoxynucleotide chain‐termination method.Results. The heavy and light chains of the C6 RF and the light chain of the G9 RF were encoded by 3 new RF‐related Ig V‐region genes. The heavy and light chains of D5 and G4 RFs were identical; most of their mutations caused amino acid substitutions.Conclusions. The RF‐related Ig V‐region gene repertoire is large and is still expanding. The data from D5 and G4 strongly suggest that these 2 RFs arise in an antigen‐driven response in rheumatoid synovium. The presumed germline V genes for C6 may represent disease‐specific RF‐related V genes.
Early‐onset osteoarthritis linked to the type ii procollagen gene. detailed clinical phenotype and further analyses of the gene
Authors: Vikkula Miikka , Palotie Aarno , Ritvaniemi Pertti , Ott JÜRg , Ala‐Kokko Leena , Sievers Ulla , Aho Kimmo , Peltonen Leena 
Published: February 2007

AbstractObjective. To specify in detail the clinical phenotype in 2 Finnish families demonstrating linkage between the type II procollagen gene (COL2A1) and osteoarthritis (OA). We also reevaluated the linkage and screened the exon sequences of the COL2A1 gene for mutations.Methods. We used single‐stranded conformation polymorphism and denaturing gradient‐gel electrophoresis techniques for the analyses.Results. The patients' phenotype represented typical, but early‐onset, OA. There was no clinical or radiographic evidence of chondrodysplasia. No mutation in the protein‐coding regions of the COL2A1 gene could be identified. However, the linkage analysis with a new multiallelic marker resulted in a statistically more significant logarithm of odds (LOD) score than has been reported.Conclusion. Familial OA with classic clinical and radiographic findings is tightly linked to the COL2A1 gene. Systematic screening of the 54 exons did not, however, reveal any mutations; this suggests that the mutation may lie in the promoter region or within the introns of this 35‐kb gene.
Localized scleroderma progressing to systemic disease. case report and review of the literature
Authors: Birdi Nina , Laxer Ronald M. , Thorner Paul , Fritzler Marvin J. , Silverman Earl D. 
Published: February 2007

AbstractWe describe a 15‐year‐old girl with biopsy‐proven morphea who developed progression to systemic disease 2 years after initial presentation. In contrast to other reported patients with localized scleroderma, some of whom have had mild, nonprogressive systemic involvement, this patient developed severe, debilitating disease, with skin tightness, sclerodactyly, esophageal involvement, restrictive pulmonary disease, and myopathy. From the time of her initial evaluation, the patient was positive for antinuclear antibodies (ANA), which were shown to be primarily directed against the Ku antigens. This observation suggests that ANA may be a prognostic indicator for progression to systemic disease.
Primary systemic amyloidosis masquerading as giant cell arteritis. case report and review of the literature
Authors: Rao Jaya K. , Allen Nancy B. 
Published: February 2007

AbstractAmyloidosis is a rare disease in which a fibrillar protein is deposited in multiple human tissues. Of the 4 subtypes, the most common type involving rheumatic disease features is hemodialysis‐associated amyloidosis. Herein we describe an elderly man who presented with symptoms of giant cell arteritis or systemic vasculitis and was found to have amyloidosis as demonstrated on muscle, nerve, and temporal artery biopsy.
Evidence suggesting that health education for self‐management in patients with chronic arthritis has sustained health benefits while reducing health care costs
Authors: Lorig Kate R. , Mazonson Peter D. , Holman Halsted R. 
Published: February 2007

AbstractObjective. To determine the effects of the Arthritis Self‐Management Program 4 years after participation in it.Methods. Valid self‐administered instruments were used to measure health status, psychological states, and health service utilization.Results. Pain had declined a mean of 20% and visits to physicians 40%, while physical disability had increased 9%. Comparison groups did not show similar changes. Estimated 4‐year savings were $648 per rheumatoid arthritis patient and $189 per osteoarthritis patient.Conclusion. Health education in chronic arthritis may add significant and sustained benefits to conventional therapy while reducing costs.
The cost‐effectiveness of misoprostol for nonsteroidal antiinflammatory drug–associated adverse gastrointestinal events
Authors: Gabriel Sherine E. , Liisa Jaakkimainen R. , Bombardier Claire 
Published: February 2007

AbstractObjective. To compare, in a Canadian health care setting, the costs and consequences of 3 strategies of misoprostol prophylaxis for osteoarthritis patients: prophylaxis for all patients taking nonsteroidal antiinflammatory drugs (NSAIDs), for no patients taking NSAIDs, and for only elderly patients (age ≥60) taking NSAIDs.Methods. We designed a decision‐analysis model which incorporated costs (estimated with ulcer patient profiles and medical records), review, and probabilities (estimated from a companion metaanalysis, selected literature review, and Ontario Ministry of Health Statistics). Effectiveness was defined as the number of episodes of gastric ulceration requiring hospitalization or outpatient management that were averted by each strategy.Results. On average, prophylaxis cost an additional $650 for every additional gastrointestinal event prevented. Prophylaxis for elderly NSAID users was cost saving if the ulcer complication rate in this group exceeds 1.2%, or if either the charges for outpatient ulcer treatment exceed $2,000, or the 3‐month price of misoprostol is ≤90.Conclusion. Our results demonstrate that, in this setting, misoprostol prophylaxis may be highly cost effective.
Hla class ii alleles and heterogeneity of juvenile rheumatoid arthritis. drb1*0101 may define a novel subset of the disease
Authors: Ploski Rafal , Vinje Odd , S. Rønningen Kjersti , Spurkland Anne , Sørskaar Dag , Vartdal Frode , Førre øystein 
Published: February 2007

AbstractObjective. To examine the distribution of HLA class II alleles in clinically distinct juvenile rheumatoid arthritis (JRA) subsets.Methods. We typed 298 patients and 181 controls for HLA–DRB1, DQA1, DQB1, and DPB1 alleles using polymerase chain reaction and oligonucleotide probe techniques.Results. Each JRA subset was characterized by a distinct distribution of HLA class II alleles. For the persistently pauciarticular and rheumatoid factornegative polyarticular JRA subsets, certain combinations of DRB1 and DPB1 alleles were characteristic. In patients without antinuclear antibodies and chronic iridocyclitis, there was an increase of DRB1*0101/02 and DQA1*0101.Conclusion. Findings of HLA typing support clinical subdivisions of the disease and suggest the existence of a novel DRB1*0101/02 and DQA1*0101 associated disease subset.
Soluble tumor necrosis factor receptors in human inflammatory synovial fluids
Authors: Roux‐Lombard Pascale , Punzi Leonardo , Hasler Fritz , Bas Sylvette , Todesco Silvano , Gallati Harald , Guerne Pierre‐André , Dayer Jean‐Michel 
Published: February 2007

AbstractObjective. To test synovial fluid (SF) for the presence of soluble fragments originating from distinct tumor necrosis factor receptors (TNF‐sR55 and TNF‐sR75) which bind to TNF and inhibit its biologic activity.Methods. TNF‐sR55 and TNF‐sR75 were measured in 62 SF samples by specific immunoassays using monoclonal antibodies.Results. Both TNF‐sR were present in all of the SF tested. Their concentrations were higher in SF from patients with seropositive rheumatoid arthritis than in patients with other inflammatory arthritides. The relative amount of TNF‐sR75, as compared with TNF‐sR55, was higher in seropositive RA SF than in other SF.Conclusion. The balance between TNF and its specific inhibitors may be critical to the biologic outcome mediated by this cytokine.
Levels of circulating tumor necrosis factor α and interleukin‐6 in patients with rheumatoid arthritis. relationship to serum levels of hyaluronan and antigenic keratan sulfate
Authors: Manicourt Daniel‐Henri , Triki Rafak , Fukuda Kanji , Devogelaer Jean‐Pierre , Deuxchaisnes Charles Nagant De , Thonar Eugene J.‐M. A. 
Published: February 2007

AbstractObjective. To measure serum levels of tumor necrosis factor α (TNF α) and interleukin‐6 (IL‐6) in patients with rheumatoid arthritis (RA) and age‐matched control subjects and to study how these correlate with serum levels of hyaluronan (HA) and antigenic keratan sulfate (KS) and other biochemical as well as clinical indicators of disease activity.Methods. Immunoassays were used to measure levels of TNFα, IL‐6, HA, and antigenic KS in the serum of 35 patients with RA and a group of age‐ and sex‐matched control subjects. Clinical disease activity in the RA group was assessed using the Lansbury index. Drug intake was recorded and the erythrocyte sedimentation rate, and levels of fibrinogen, creatinine, bilirubin, alkaline phosphatase, lactate dehydrogenase, and aminotransferase were measured.Results. Serum levels of TNFα, IL‐6, and HA were significantly higher in the RA population than in the control group. In patients with RA, serum levels of HA correlated positively with serum levels of TNFα and with clinical joint scores, but only weakly with other laboratory parameters of inflammation. Serum levels of antigenic KS correlated negatively with levels of circulating TNFα, but much more weakly with other clinical and biochemical parameters of disease activity.Conclusion. These in vivo data support in vitro studies which have shown that TNFα is a potent stimulator of HA synthesis by synovial lining cells. The results strengthen the contention that serum HA may be a unique marker of synovial involvement and inflammation, rather than of only inflammation, in RA.
Enhanced chondrocyte destruction by lymphokine‐activated killer cells. possible role in rheumatoid arthritis
Authors: Yamaga Karen M. , Bolen Harriet , Kimura Lucille , Lance Eugene M. 
Published: February 2007

AbstractObjective. The lysis of chondrocytes, the parenchymal cells of cartilage, by lymphocytes may provide a potent mechanism by which the immune system participates in sustaining joint damage in rheumatoid arthritis (RA). We studied the capability of lymphocytes from healthy individuals and patients with arthritis to lyse chondrocytes.Methods. Peripheral blood mononuclear cells (PBMC) were tested for their ability to lyse chondrocytes in a 51Cr‐release assay. Enhancement of the chondrolytic activity was determined by preincubating the cells with T cell growth factor (TCGF) or recombinant interleukin‐2 (rIL‐2) before cytotoxic testing.Results. PBMC from healthy individuals possessed a low ability to lyse chondrocytes, whereas cells from the synovial fluid of patients with RA displayed higher chondrolytic activity. In RA, modulating factors must come into play because not all synovial fluid sample cells showed high chondrolytic activity and cells from synovial tissue had little or no lytic action on chondrocytes. Chondrolytic activities of cells from all sources, including PBMC from healthy subjects and patients with arthritis and cells isolated from synovial fluid or from the synovial tissue of RA patients, were greatly increased by incubating the cells with TCGF or rIL‐2. In contrast, treatment of chondrocytes with interferon‐γ, which enhances major histocompatibility complex gene expression, decreased the susceptibility of chondrocytes to lysis.Conclusion. These observations suggest a mechanism for joint damage in which the destruction of chondrocytes by lymphocytes is controlled by cytokines released during the inflammatory process in arthritic diseases.
Detection of increased levels of circulating intercellular adhesion molecule 1 in some patients with rheumatoid arthritis but not in patients with systemic lupus erythematosus. lack of correlation with levels of circulating vascular cell adhesion molecule 1
Authors: Mason Justin C. , Kapahi Pankaj , Haskard Dorian O. 
Published: February 2007

AbstractObjective. To compare the levels of circulating intercellular adhesion molecule 1 (cICAM‐1) and vascular cell adhesion molecule 1 (cVCAM‐1) in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).Methods. Levels of cICAM‐1 and cVCAM‐1 were measured in both plasma and synovial fluid using monoclonal antibody sandwich enzyme‐linked immunoassays.Results. Levels of both cICAM‐1 and cVCAM‐1 were significantly increased (P < 0.001) in RA patients compared with normal controls. In contrast, only cVCAM‐1, and not cICAM‐1, was increased in patients with SLE. Levels of cICAM‐1 and cVCAM‐1 were significantly elevated in synovial fluid compared with plasma in paired samples from patients with RA. There was no correlation between levels of cICAM‐1 and levels of cVCAM‐1, in either plasma or synovial fluid. Whereas levels of cVCAM‐1 correlated significantly with the erythrocyte sedimentation rate (ESR) and C‐reactive protein level in RA patients and with the ESR in SLE patients, no significant correlations were found between cICAM‐1 and either of these indices of disease activity.Conclusion. These observations indicate that levels of cICAM‐1 and cVCAM‐1 reflect separate pathophysiologic processes. Both may be useful markers for the diagnosis and management of patients with rheumatic diseases.
Different manifestations of the antiphospholipid antibody syndrome in a family with systemic lupus erythematosus
Authors: May Kimberly P. , West Sterling G. , Moulds Joann , Kotzin Brian L. 
Published: February 2007

AbstractObjective. Familial associations of the antiphospholipid antibody syndrome (APS) offer the opportunity to study genetic mechanisms of autoantibody production and disease, but are unusual. We identified a family, including identical twins and their mother, in which all members had systemic lupus erythematosus (SLE) and presented with different manifestations of the APS.Methods. Review of case histories and clinical laboratory results, antiphospholipid antibody (aPL) studies, complement C4 protein and gene analysis, and HLA typing of family members were performed.Results. Each of the 3 family members presented with a different clinical association of the APS. These various clinical presentations were closely temporally related. No particular aPL activity could be separated out that would account for the different manifestations, although the twin with thrombocytopenia and livedo reticularis had a strikingly high IgM anticardiolipin antibody level. C4A or C4B deficiencies could not be implicated in the autoimmune process. However, the mother and the twins shared the HLA haplotype that included the class II antigens DR4, DRw53, and DQw7, which has previously been associated with aPL production.Conclusion. This family study emphasizes the different clinical associations of aPL production in SLE. In addition to genetic influences that appear to include HLA class II antigens, the clinical presentations also suggest an environmental trigger.
The quantitation of a native chondroitin sulfate epitope in synovial fluid lavages and articular cartilage from canine experimental osteoarthritis and disuse atrophy
Authors: Ratcliffe Anthony , Shurety Wenda , Caterson Bruce 
Published: February 2007

AbstractObjective. Previous studies have shown the presence of a native chondroitin sulfate epitope in articular cartilage proteoglycans from canine knee joints with experimental early osteoarthritis (OA), but not in normal cartilage. The objective of this study was to quantitate the native epitope recognized by monoclonal antibody 3‐B‐3 in synovial fluids and articular cartilage of diseased joints.Methods. An immunoassay with monoclonal antibody 3‐B‐3, which recognizes a native chondroitin‐6‐sulfate structure, was developed and used to analyze synovial fluid lavage material and extracts of articular cartilage from canine knee joints with early experimental OA or with mild disuse atrophy, and from control animals.Results. The concentration of epitope in the OA fluids was elevated 33–35‐fold, and in the OA articular cartilage extracts it was elevated > 200‐fold, compared with samples from the control group. No significant difference was detected in the levels of 3‐B‐3 epitope in the synovial fluid lavage material or cartilage extracts from the joints of the disuse group versus the control group.Conclusion. The native 3‐B‐3 epitope in articular cartilage and synovial fluids may be a specific marker of ongoing anabolic events in early degenerative joint disease.
Marital status and the progression of functional disability in patients with rheumatoid arthritis
Authors: Ward Michael M. , Paul Leigh J. 
Published: February 2007

AbstractObjective. To determine if marital status is associated with differences in rates of progression of functional disability in patients with rheumatoid arthritis (RA).Methods. A community cohort of 282 persons with RA was followed prospectively for up to 9.5 years. The progression of functional disability over time was determined using the Health Assessment Questionnaire Disability Index, which was completed by study participants every 6 months.Results. At study entry, the Disability Index was 1.1 ± 0.8 (mean ± 1 SD) (possible range 0–3) among the 188 married participants and 1.3 ± 0.9 among the 94 unmarried participants. Over time, the rate of progression of functional disability was generally higher among unmarried participants. However, the extent of this difference varied somewhat over the disease course, with rates of progression higher among unmarried than among married participants during years 5–7 and years 17–29 of RA. Overall estimated rates of progression, adjusted for the effects of other sociodemographic factors, were 0.03 Disability Index units per year in unmarried participants and 0.01 Disability Index units per year in married participants (P < 0.0001).Conclusion. Marriage, possibly reflecting the influence of social support, is associated with a lower rate of progression of functional disability in persons with RA.
Regulation of the expression of intercellular adhesion molecule 1 in cultured human endothelial cells derived from rheumatoid synovium
Authors: Gerritsen Mary E. , Kelley Keith A. , Ligon Gwenda , Perry Carol A. , Shen Chien‐Ping , Szczepanski Andrew , Carley William W. 
Published: February 2007

AbstractObjective. To examine the regulation of intercellular adhesion molecule 1 (ICAM‐1) in human synovial microvascular endothelial cells (HSE) and human umbilical vein endothelial cells (HUVE) upon exposure to a variety of agents.Methods. Cultured endothelial cells were treated with various cytokines alone and in combination. The expression of ICAM‐1 was evaluated at several levels, including an investigation of messenger RNA (mRNA) and surface protein expression.Results. Treatment of HSE with interleukin‐1α (IL‐1α) or tumor necrosis factor α (TNFα) resulted in minimal increases in ICAM‐1 expression, in contrast to findings with HUVE. Incubation of HUVE or HSE with IL‐1 or TNF in combination with interferon‐γ (IFNγ) greatly potentiated the increase in ICAM‐1 surface expression. The synergistic effect of IFNγ and TNF was confirmed by several methods, including a cell‐based enzyme‐linked immunosorbent assay, fluorescence‐activated cell sorting, immunofluorescence staining, and determination of mRNA levels. IFNγ also augmented the actions of several other agonists on HSE, i.e., IL‐4, lipopolysaccharide, and TNFβ/lymphotoxin. Immunoprecipitation of TNFα + IFNγ–stimulated, 125I‐labeled HSE cells with anti–ICAM‐1 revealed a single 90‐kd band, similar in size to ICAM‐1 from HUVE treated in an identical manner. Unexpectedly, IFNγ alone was a potent stimulus for HSE ICAM‐1 mRNA synthesis, but was relatively ineffective in HUVE.Conclusion. These studies indicate that IFNγ plays a critical synergistic role in the regulation of ICAM‐1 expression in human synovial endothelial cells.