bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allotypic dependency of the specificity and avidity of human monoclonal igm rheumatoid factors derived from rheumatoid synovial cells
Authors: Robbins Dick L. , Kenny Thomas P. , Snyder Lisa L. , Ermel Richard W. , Larrick James W. 
Published: February 2007

AbstractObjective. To better understand the genetic derivation and pathogenicity of rheumatoid factor (RF) molecules in rheumatoid arthritis (RA), we have focused our studies on rheumatoid synovial cells (RSC).Methods. Five monoclonal human IgM rheumatoid factor (mRF)—secreting hybridomas were produced from the RSC of an RA patient. Fine subclass specificities and avidities of these RSC mRFs were compared with several paraprotein monoclonal IgM RFs using direct binding (reactivity) and competitive inhibition (specificity and avidity) enzyme‐linked immunosorbent assays.Results. The following observations were made: 1) RSC mRF had greater avidity for IgG than did paraprotein mRF; 2) 4 of the 5 RSC RF were highly avid for IgG3; and, 3) the avidity of RSC RF binding for IgG3 was highest for IgG molecules expressing the G3m(5) allotype.Conclusion. We conclude that RSC RF have different specificities and avidities than do paraprotein RF. This may suggest an antigen‐driven process in RA synovium, with the production of higher‐avidity IgG3m(5)‐specific RSC RF, which could have special pathogenetic importance.
Assessment of clinical competence of medical students by using standardized patients with musculoskeletal problems
Authors: Connell Karen J. , Sinacore James M. , Schmid Frank R. , Chang Rowland W. , Perlman Susan G. 
Published: February 2007

AbstractObjective. To assess medical students' clinical competence in addressing musculoskeletal problems.Methods. Nineteen junior medical students completed 2 standardized patient‐based tests structured to capture their clinical decisions from undiagnosed chief complaint to management.Results. No student approached the highest possible score on either test, and the students as a group received less than half the possible points on 5 important aspects of diagnostic reasoning.Conclusion. Standardized patient‐based tests can be structured to provide enlightening information about medical students' clinical competence with regard to musculoskeletal problems.
Linkage studies of hla and primary sjögren's syndrome in multicase families
Authors: Mrcp Helen Foster, , Stephenson Anthea , Walker David , Cavanagh Gary , Kelly Clive , Griffiths Ian 
Published: February 2007

AbstractObjective. To define the role of HLA–DR pheno‐type in the expression of primary Sjögren's syndrome (SS).Methods. A family study of Caucasian probands with definite primary SS was conducted. Relatives with features of primary SS were classified according to the Fox criteria. Several types of linkage analysis between primary SS and HLA haplotype (HLA–A, B, and DR) were performed.Results. A trend toward haplotype sharing between affected siblings was evident for definite/probable primary SS when analyzed by the Green and Woodrow method. This reached statistical significance when data from other published family studies were included. LOD scores and analyses using the Penrose method showed little evidence of linkage.Conclusion. In view of the strong association with HLA‐DR3, these results suggest that the HLA‐DR3 allele is an important susceptibility factor for expression of primary SS in Caucasians. The apparent haplotype sharing may be a consequence of this association. The potential influence of other genetic factors (major histocompatibility complex [MHC] and non‐MHC) is discussed.
A comparison of the effect of transforming growth factor β1 on pyrophosphate elaboration from various articular tissues
Authors: Rosenthal Ann K. , Mccarty Brian A. , Cheung Herman S. , Ryan M. 
Published: February 2007

AbstractObjective. The purpose of this study was to determine the effect of transforming growth factor β1 (TGFβ1) on inorganic pyrophosphate (PPi) elaboration from articular tissues to better understand the pathophysiology of calcium pyrophosphate dihydrate (CPPD) crystal deposition in the joint.Methods. PPi was measured in the media of adult porcine articular tissue in organ culture and monolayer cultures.Results. TGF/β1 strongly stimulated PPi elaboration by porcine fibrocartilage and hyaline cartilage. It modestly increased PPi elaboration by ligament, and had no effect on PPi elaborated by synovium. Of all cell types tested in cell culture, only chondrocytes responded to TGF/β1 by significantly increasing PPi elaboration.Conclusion. TGF/β1 stimulates PPi elaboration from hyaline cartilage, fibrocartilage, and ligament, indicating that there is in situ CPPD crystal formation in these tissues. The ability of tissues to respond to TGFβ1 by increasing PPi elaboration correlates with the prevalence of CPPD crystal deposition found clinically. The unique response of chondrocyte monolayers to TGF/β1 reinforces the key role of the chondrocyte in PPi elaboration in the joint. These findings support an etiologic role for responsiveness to TGFβ1 in CPPD disease.
Vh family utilization by igg anti‐dna–secreting lymphocytes derived from autoimmune mrl‐lpr/lpr mice
Authors: Klinman Dennis M. , Dellacqua Dale K. , Conover Jacqueline , Huppi Konrad 
Published: February 2007

AbstractObjective. To evaluate the heterogeneity of the IgG anti‐DNA autoantibody response of MRL/lpr mice.Methods. B cell clones were grown on nitrocellulose membranes. Those producing IgG anti‐DNA antibodies were identified by a modified enzyme‐linked immunospot assay, and their utilization of IgVH genes was determined by hybridization.Results. Four hundred sixty‐eight IgG anti‐DNA–secreting colonies were derived from 9 autoimmune MRL/lpr mice. Individual VH families contributed to anti‐DNA production at a frequency roughly proportional to their representation in the expressed repertoire (except for the more frequent use of VH 7183 and less frequent use of VH 36‐60). In individual mice, anti‐DNA antibodies were encoded by 2–5 different IgVH families, with no single family constituting more than 27–65% of any animal's anti‐DNA response.Conclusion. The IgG anti‐DNA response of individual MRL/lpr mice is oligoclonal.
Ai/learn/rheumatology. a comparative study of computer‐assisted instruction for rheumatology
Authors: Bridges Alan J. , Reid John C. , Cutts James H. , Wood Susan Hazel , Sharp Gordon C. , Mitchell Joyce A. 
Published: February 2007

AbstractObjective. To assess the effectiveness of AI/ LEARN/Rheumatology, a computer‐controlled interactive videodisc system for teaching.Methods. We assessed improvement in knowledge about rheumatic diseases, using a pretest and posttest in a control year and a treatment year. The subjects were medical students and postgraduate trainees taking the rheumatology elective. The control year used traditional lectures and the standard rheumatology curriculum. The treatment year used AI/LEARN/ Rheumatology in place of lectures on rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis.Results. The trainees showed significant improvement in knowledge in both the control year and the treatment year (P < 0.0001 for both). The average time spent using AI/LEARN/Rheumatology was similar to the time spent in lectures (3 hours). The number of patient consultations in which trainees participated was lower in the treatment year than in the control year; however, the adjusted posttest scores using the pretest as a covariate tended to be higher in the treatment year (P = 0.10). Analysis of covariance of the adjusted posttest scores for the treatment year only showed that the trainees who spent more time using AI/LEARN/Rheumatology learned more (r = 0.57). Trainees felt that AI/LEARN/Rheumatology was the most helpful educational experience of the elective.Conclusion. AI/LEARN/Rheumatology is an effective means of teaching about the rheumatic diseases. It has many advantages: availability for independent study, effective use of trainee's time, and liberation of faculty time from lectures. Trainees enjoyed using AI/LEARN/Rheumatology.
Subpopulations of primed t helper cells in rheumatoid arthritis
Authors: Matthews Nick , Emery Paul , Pilling Darrell , Akbar Arne , Salmon Mike 
Published: February 2007

AbstractObjective. To analyze subsets of primed T helper cells, defined by expression of the CD45RB isoform of the leukocyte common antigen, in the blood and synovial fluid (SF) of patients with rheumatoid arthritis (RA).Methods. Three‐color immunofluorescence was used to study CD45 isoform expression by peripheral blood and SF CD4+ T cells.Results. CD45 isoform expression in the peripheral blood of patients with either RA or reactive arthritis did not differ from that in healthy controls. SF T cells from both RA patients and reactive arthritis patients were almost exclusively primed (CD45RO+) cells. RA SF T cells expressed very low levels of CD45RB; this is the most highly differentiated subset of primed cells. Patients with acute reactive arthritis showed higher levels of CD45RBbright cells in their synovial fluid.Conclusion. The highly selected cell population in SF, representing one subset of primed cells, may relate to the apparent functional abnormalities of cells from this site in patients with RA.
Familial versus sporadic ankylosing spondylitis. two different diseases?
Authors: Calin Andrei , Gail Kennedy L. , Edmunds Laurel , Will Rob 
Published: February 2007

AbstractObjective. To define potential differences and the possible contribution of susceptibility or severity genes in familial versus sporadic ankylosing spondylitis (AS).Methods. Three hundred twenty patients with AS were studied: 160 who had first‐degree relatives with AS (familial) and 160 age‐ and sex‐matched controls who had no first‐degree relative with the disease (sporadic). Disease expression in the two groups was evaluated using an index of physical, psychological, and social functioning (the Arthritis Impact Measurement Scales [AIMS]) and an assessment of spinal mobility.Results. Familial disease was significantly milder than sporadic disease as assessed by all measures, e.g., spinal mobility score (mean 4.08 versus 4.65, P < 0.038), AIMS overall impact score (mean 2.63 versus 3.59, P = 0.002), AIMS physical activity score (4.19 versus 5.10 [P = 0.004]), AIMS social function score (4.02 versus 4.60, P = 0.023), and AIMS pain score (4.15 versus 5.33, P = 0.002).Conclusion. The greater prevalence of AS in at‐risk families may be explained by the occurrence of more AS “susceptibility” genes in those families, whereas the more severe disease, seen in patients with sporadic AS, is conferred by the presence of more “severity” genes than “susceptibility” genes.
Gastrointestinal regulatory peptides in systemic sclerosis
Authors: Åkesson Anita , Ekman Rolf 
Published: February 2007

AbstractObjective. Gastrointestinal involvement commonly occurs in systemic sclerosis (SSc), but its pathogenesis is not well understood. Since there is evidence of a defect in neurotransmitter release, we were interested in examining the relationship between gastrointestinal dysfunction and plasma concentrations of gastrointestinal regulatory peptides in patients with SSc. We studied 43 consecutive patients, 18 with diffuse and 25 with limited cutaneous disease.Methods. Levels of corticotropin‐releasing hormone (CRH), gastrin, motilin, neuropeptide Y (NPY), and peptide YY (PYY) were determined by radioimmunoassay and high‐performance liquid chromatography (HPLC).Results. Plasma concentrations of CRH, motilin, NPY, and PYY were significantly increased among SSc patients compared with healthy control subjects, and HPLC‐characterization of motilin, NPY, and PYY showed a different pattern of fragments. No correlation was found between esophageal hypomotility and the concentration of peptide. Acid output did not correlate with gastrin levels, but was more often increased in patients with increased CRH and NPY values. Fat malabsorption, assessed by the triolein breath test, was more common among patients with increased motilin and PYY.Conclusion. This study shows that elevated peptide concentrations commonly occur in patients with SSc. Since regulatory peptides are involved in gastrointestinal motility, secretion, and absorption, further characterization of this neuroendocrine system may help in understanding the complex regulation of gastrointestinal dysfunction in SSc.
Calcium pyrophosphate dihydrate crystal deposition in synovium. relationship to collagen fibers and chondrometaplasia
Authors: Beutler Anna , Rothfuss Susan , Clayburne Gilda , Sieck Marie , Ralph H. Schumacher 
Published: February 2007

AbstractObjective. Reasons for apparent primary deposition of calcium pyrophosphate dihydrate (CPPD) crystals in some synovial membranes have not been systematically examined. We undertook the present study to investigate for and compare possible cellular and matrix factors related to the presence of these crystals in synovium and cartilage.Methods. Ten synovial membrane specimens and 6 cartilage specimens were obtained at the time of joint surgery from 10 patients with CPPD crystal deposition disease, for light microscopic (LM) and electron microscopic (EM) studies.Results. In all synovial and cartilage specimens, we found many of the small CPPD crystals aligned on or in parallel to collagen fibers, as seen by EM. In 9 of the 10 crystal‐containing synovia, we found foci of chondrometaplasia adjacent to CPPD, by LM. In 7 of the synovia, including the one without LM evidence of chondrometaplasia, we observed the presence of chondrocyte‐like cells by EM. We did not note any predictable relationship between the crystals and matrix vesicles, either in synovium or in cartilage.Conclusion. Our EM findings provide evidence of the relationship of small CPPD‐like crystals, presumably early forms, to collagen fibers both in synovium and in cartilage. By LM and EM, we also demonstrate evidence of a close association between chondrometaplasia and CPPD deposits in synovium. We suggest that chondrometaplasia might be responsible for synovial CPPD formation in predisposed patients. Both the collagen fibers and chondrocyte‐like cells seem to be involved in the primary formation of CPPD deposits in the synovium as well as in the cartilage.
Levels of synovial fluid interleukin‐1 receptor antagonist in rheumatoid arthritis and other arthropathies. potential contribution from synovial fluid neutrophils
Authors: Malyak Mark , Swaney Robert E. , Arend William P. 
Published: February 2007

AbstractObjective. To measure synovial fluid (SF) levels of interleukin‐1 receptor antagonist (IL‐1ra) and to determine the capacity of SF neutrophils (PMN) to synthesize and release IL‐1ra.Methods. A sensitive and specific enzyme‐linked immunosorbent assay was used to measure SF IL‐1ra protein concentrations and IL‐1ra production by isolated SF PMN.Results. SF IL‐1ra levels were elevated in 13 of 16 samples from patients with rheumatoid arthritis (RA) (mean 17.1 ng/ml), in 6 of 18 samples from patients with infectious or inflammatory, non‐RA arthropathies (mean 10.6 ng/ml), and in none of 11 noninflammatory SF samples. SF IL‐1ra levels correlated with SF PMN concentrations (r = 0.680, P < 0.00001). Isolated SF PMN contained preexisting IL‐1ra protein in the absence of messenger RNA (mRNA). In addition, both lipopolysaccharide and granulocyte‐macrophage colonystimulating factor induced modest increases in IL‐1ra mRNA by cultured SF PMN.Conclusion. IL‐1ra levels are increased in >80% of RA SF samples. SF PMN produce IL‐1ra, possibly contributing to the levels of IL‐1ra present within the SF.
Elevated synovial fluid levels of interleukin‐6 and tumor necrosis factor associated with early experimental canine osteoarthritis
Authors: Venn G. , Nietfeld J. J. , Duits A. J. , Brennan F. M. , Arner E. , Covington M. , Billingham M. E. J. , Hardingham T. E. 
Published: February 2007

AbstractObjective. To measure levels of cytokines, proteases, and glycosaminoglycans (GAG) in synovial fluid (SF) from the knees of animals with experimental osteoarthritis (OA) and from their contralateral (control) knees, and to compare and correlate these values with each other as well as with measures of proteoglycan synthesis in the corresponding articular cartilage. This study will help to identify cytokines of potential importance in the early stages of the development of OA.Methods. OA was induced in 12 mature animals by sectioning the anterior cruciate ligament. After 3 months, SF from the operated and contralateral (control) knee joints was assayed for interleukin‐6 (IL‐6), tumor necrosis factor (TNF), IL‐1, latent metalloproteinase, and sulfated GAG. Proteoglycan synthesis in the corresponding articular cartilage was also measured.Results. IL‐6 levels in SF from the operated joint compared with the control joint were significantly elevated in 11 of 12 animals. TNF levels were also elevated in 10 of 11 SF samples from operated joints, but to a lesser extent than those of IL‐6. IL‐1 and IL‐1 inhibitors were undetectable in either the operated or control joint SF. The GAG concentration was elevated in SF from experimental OA joints. This elevation correlated with that of TNF, but not IL‐6. There was no significant difference in the concentration of APMA‐activatable metalloproteinase. The rate of proteoglycan synthesis was higher in the cartilage from the operated joint in 8 of 12 animals, and the mean rate of synthesis was significantly higher than in the control joint. There was a positive correlation between this increase in cartilage proteoglycan synthesis (operated versus control) and the increase in SF IL‐6, but there was no correlation with the levels of TNF or GAG.Conclusion. This is the first study of SF levels of cytokines in early experimental OA. Our results show surprisingly high levels of IL‐6 in operated joints, where the cytokine could act directly on the chondrocytes, and thus play a role in mediating their responses to cartilage injury.
Autoantibodies to chromatin components in juvenile rheumatoid arthritis
Authors: Burlingame Rufus W. , Rubin Robert L. , Rosenberg Alan M. 
Published: February 2007

AbstractObjective. To characterize autoantibodies to chromatin components in patients with juvenile rheumatoid arthritis (JRA).Methods. The sera of 50 children with JRA were analyzed for antinuclear antibodies (ANA) by immunofluorescence and enzyme‐linked immunosorbent assay (ELISA) techniques.Results. By immunofluorescence, ANA and antibodies to high‐mobility group proteins or to DNA‐free histones were common in patients with pauciarticular JRA and rheumatoid factor–positive polyarticular JRA. However, reactivity with histone–DNA complexes was rare.Conclusion. Because antihistone antibodies detected by ELISA failed to bind chromatin or other histone–DNA complexes, they are not likely to represent the immunofluorescent ANA activity in serum.
Bilateral tumoral infiltration of the achilles tendons revealing chronic myelomonocytic leukemia
Authors: Chevalier Xavier , Hermine Olivier , Rahmouni Alain , Voisin Marie‐Catherine , Laatiri Mohamed , Gaulard Phillipe , Larget‐Piet Bruno , Pignon Jean‐Michel 
Published: February 2007

AbstractExtrahematologic manifestations, such as symptoms of rheumatic disease, have been recorded in association with myelodysplastic syndromes, including chronic myelomonocytic leukemia (CMML). We report the case of a 51‐year‐old woman with tumoral infiltration of the Achilles tendons bilaterally, indicating CMML. This diagnosis was confirmed at postmortem examination.
Restricted cytokine expression in rheumatoid arthritis
Authors: Chen E. , Keystone E. C. , Fish E. N. 
Published: February 2007

AbstractObjective. To determine the cytokine profile of the phenotypically activated T cell in rheumatoid arthritis (RA) synovium.Methods. Interleukin‐2 (IL‐2), IL‐2 receptor (IL‐2R), IL‐6, IL‐4, and interferon‐γ (IFNγ) gene expression was examined in T cells from freshly isolated synovial fluids (SF) and synovial tissues (ST) from patients with RA. Estimates of baseline expression were determined using unstimulated peripheral blood (PB) T cells from healthy individuals. The corresponding positive controls were phytohemagglutinin‐activated tonsil T cells.Results. In studies of paired PB and SF T cell samples from 17 RA patients, IL‐2 messenger RNA (mRNA) levels in only 1 PB and 3 SF samples were more than 2 standard deviations above the mean of levels in unstimulated PB from healthy donors. Similarly, only 5 PB and 7 SF samples exhibited elevated IL‐2R mRNA levels. IFNγ gene expression was not detected in any of the paired RA PB or SF samples. Fractionated T cells from 12 RA ST were screened with similar results: Only 1 of 12 samples exhibited IL‐2 mRNA levels more than 2 standard deviations above levels in baseline controls. IL‐2R mRNA levels were low or not detected, and IFNγ mRNA was absent. Subsequent studies showed that IL‐4 and IL‐6 gene expression levels were also low in RA tissues compared with tonsil T cell–positive controls.Conclusion. These data provide evidence for restricted cytokine expression in the T cell population in RA tissues.
Rheumatoid factors from patients with rheumatoid arthritis react with tryptophan 60 and 95, lysine 58, and arginine 97, on human β2‐microglobulin
Authors: Williams Ralph C. , Malone Christine C. , Harley John B. 
Published: February 2007

AbstractObjective. To define precise epitopes on human β2‐microglobulin (β2m) reacting with polyclonal IgM rheumatoid factors (RF) from patients with rheumatoid arthritis (RA).Methods. Ten polyclonal RF were tested for their human β2m epitope–binding specificities using the entire 99–amino acid sequence synthesized as overlapping 7‐mers in an enzyme‐linked immunosorbent assay. Glycine substitution for each residue within RF‐reacting linear regions was employed to define major reactive sites.Results and Conclusion. Major β2m residues contributing to RF reactivity were tryptophans at positions 60 and 95, lysine at 58, and arginine at position 97.
Generation and molecular analyses of two rheumatoid synovial fluid–derived IgG rheumatoid factors
Authors: Lu Edward W. , Deftos Michael , Olee Tsaiwei , Huang De‐Feng , Soto‐Gil Rafael W. , Carson Dennis A. , Chen Pojen P. 
Published: February 2007

AbstractObjective. To study the Ig genes that encode IgG rheumatoid factor (IgG‐RF) from rheumatoid synovial fluid.Methods. We used rheumatoid synovial fluid B cells to generate IgG‐RF–secreting hybridomas. We then characterized their binding properties and determined their nucleotide sequences.Results. Two monospecific IgG‐RFs were obtained. Sequence analysis of the RFs revealed a new Vλ gene family (designated Vλ9) and extensive somatic diversification, including a duplication‐insertion of 18 nucleotides (6 amino acid residues) into a hypervariable region.Conclusion. The data provide further support for an antigen‐driven response in the sustained production of potentially pathogenic IgG‐RFs in rheumatoid synovium.