bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil trafficking into inflamed joints in patients with rheumatoid arthritis, and the effects of methylprednisolone
Authors: Youssef Peter P. , Cormack John , Evill Charles A. , Peter Daryl T. , Roberts‐Thomson Peter J. , Ahern Michael J. , Smith Malcolm D. 
Published: February 2007

AbstractObjective. To investigate the trafficking of circulating blood neutrophils and synovial fluid neutrophils in rheumatoid arthritis (RA) patients and the influence of a 1,000‐mg intravenous pulse of methylprednisolone succinate (MP).Methods. Neutrophils were isolated from the circulation and from the knee synovial compartments of subjects with RA. Circulating neutrophils were labeled with technetium‐99m hexametazime (99mTc‐HMPAO) and reinjected intravenously. Synovial fluid neutrophils were labeled with indium‐111 oxine and reinjected into the knee from which they were isolated. Gamma camera images were obtained at intervals up to 24 hours post MP. Each patient had a baseline study (no MP) and a study in which MP was administered either 4 hours before (2 patients), 10 minutes before (1 patient), or 30 minutes to 1.5 hours after (6 patients) injection of the radiolabeled neutrophils. Subsequent analysis allowed quantitation of the neutrophil uptake into and clearance from the knee as a function of time.Results. Nine patients who had not received glucocorticoids in the previous 3 months were studied. MP significantly decreased neutrophil ingress in 13 of the 16 knees studied (almost total inhibition in 5 knees), and this occurred within 1.5 hours of MP administration in all except 1 knee. At 24 hours after MP administration, there was a significant increase in visual analog scale (VAS) scores for well‐being and significant decreases in scores on the modified Health Assessment Questionnaire (P < 0.05), tender joints (P < 0.005), VAS for pain (P < 0.005), and generalized stiffness (P < 0.005), as well as a decrease in the C‐reactive protein level (P < 0.05). MP had no effect on neutrophil egress (2 patients). Two additional patients who were receiving oral glucocorticoids were studied. One of them was clinically unresponsive to oral prednisolone, and MP had no effect on neutrophil ingress. The other patient showed no neutrophil ingress during the baseline study. This was confirmed by the presence of a noninflammatory synovial fluid at arthrocentesis.Conclusion. Neutrophil ingress into and egress from inflamed joints can be accurately monitored using radiolabeled neutrophils and quantitative gamma camera imaging. MP rapidly and substantially decreases neutrophil ingress into inflamed joints. In contrast, MP has no effect on neutrophil egress from the joint.
Identification of a nucleotide pyrophosphohydrolase from articular tissues in human serum
Authors: Cardenal Antonio , Masuda Ikuko , Haas Arthur L. , Ono Wataru , McCarty Daniel J. 
Published: February 2007

AbstractObjective. To characterize the nucleotide pyro‐phosphohydrolase (NTPPHase) in human serum.Methods. NTPPHase activity and kinetic analysis were performed using thymidine monophosphate paranitrophenyl ester (TMPNP) or 32Pγ‐labeled ATP as substrate. Sera were chromatographed (dye column), and peak fractions were analyzed kinetically and by immunoblot using antibodies to 127‐kd articular cartilage vesicle (ACV) NTPPHase as well as to PC‐1 and to 58 kd, two plasma membrane ecto‐NTPPHases. Enzyme activity was measured before and after sample ultracentrifugation.Results. NTPPHase activity was found in all sera tested (2 normal subjects, 9 arthritis patients). Specific activity was increased 9–32‐fold after chromatography; 60–80% of total activity was recovered in a single peak containing an ∼100‐kd soluble peptide related to the 127‐kd ACV enzyme. The apparent Km of this peptide (TMPNP) was virtually identical to that of the porcine ACV 127‐kd enzyme. No immunoreactivity against PC‐1 or 58‐kd NTPPHase was found.Conclusion. Human serum NTPPHase is derived from 127‐kd ACV‐related enzyme.
Sensitivity and specificity of anti‐Jo‐1 antibodies in autoimmune diseases with myositis
Authors: Vázquez‐Abad Dolores , Rothfield Naomi F. 
Published: February 2007

AbstractObjective. To determine the sensitivity and specificity of anti‐Jo‐1 in systemic sclerosis (SSc) patients with and without myositis.Methods. Immunoblots on HeLa nuclei were used to screen sera from 554 consecutive connective tissue disease patients. Those who had 45–55‐kd bands, all patients with polymyositis/dermatomyositis (PM/DM), and a random selection of SSc, Raynaud's disease, systemic lupus erythematosus, and rheumatoid arthritis patients were also studied by anti–Jo‐1 enzyme‐linked immunosorbent assay and by immunoblots on rabbit pooled aminoacyl‐transfer RNA synthetase.Results. Anti–Jo‐1 was present only in 8 of the 40 PM/DM patients.Conclusion. Anti–Jo‐1 is specific for PM/DM.
Numerical scoring systems for the anatomic evolution of osteoarthritis of the finger joints
Authors: Verbruggen Gust , Veys Eric M. 
Published: February 2007

AbstractObjective. To assess and score the progression of osteoarthritis (OA) of the distal and proximal interpha‐langeal (DIP and PIP) and metacarpophalangeal (MCP) joints.Methods. Forty‐six patients with OA of the finger joints were followed up for 3 years; 36 of them were followed up for 5 years. Posteroanterior radiographs of the hands were obtained at the start of this prospective study and at yearly intervals. The scoring systems used were based on the increased incidence of OA during consecutive years in previously normal joints, the radiologic progression of the anatomic lesions in the affected finger joints, and the consecutive pathologic phases recognized in the course of the disease.Results. Significant increases both in the numbers of affected DIP, PIP, and MCP joints per subject and in the anatomic progression of the disease (changes in osteophyte growth, loss of joint space, and subchondral cysts or sclerosis) in the different finger joints of each patient were recorded during the 3 and 5 years of followup. In ∼40% of the patients, the classic picture of OA was complicated by erosive changes, which preceded a period in which repair phenomena in the “eroded” finger joints led to the generation of a new subchondral plate covered by cartilaginous tissue. Huge osteophytes were then responsible for the nodular aspect of the affected finger joints.Conclusion. OA of the finger joints is progressive in nature and passes through predictable phases. The recognition of and the attribution of a score to these respective phases made assessing the progression of OA less time‐consuming and led to the same conclusions as when the anatomic progression was scored.
Cryocrystalglobulinemia as a cause of systemic vasculopathy and widespread erosive arthropathy
Authors: Papo Thomas , Musset Lucile , Bardin Thomas , Bucki Barbara , Jorgensen Christian , Dion Elisabeth , Quillard Alain , de Gennes Christian , Sany Jacques , Godeau Pierre , Piette Jean‐Charles 
Published: February 2007

AbstractThis report describes the case of a woman who was admitted to the hospital for highly destructive axial and peripheral arthropathy in association with acute malignant hypertension and skin purpura. Type I IgG K serum cryoglobulinemia was identified and was classified as a monoclonal gammopathy of unknown significance. Cryoglobulin was shown to crystallize in the serum and synovium fluid and was responsible for both granulomatous microcrystalline synovial inflammation and occlusive vasculopathy in the kidneys and skin. Cryocrystalglobulinemia pathogenicity and therapeutic implications are discussed.
Failure of low‐dose intravenous immunoglobulin therapy to suppress disease activity in patients with treatment‐refractory rheumatoid arthritis
Authors: Kanik Keith S. , Yarboro Cheryl H. , Naparstek Yaakov , Plotz Paul H. , Wilder Ronald L. 
Published: February 2007

AbstractObjective. Treatment with high‐dose (400 mg/kg/day) intravenous immunoglobulin (IVIg) shows benefit in many autoimmune diseases but is very expensive. Low‐dose IVIg has also been shown to be effective in inhibiting adjuvant arthritis in the rat. This pilot, randomized, double‐blind, placebo‐controlled trial was conducted to assess the use of low‐dose IVIg in patients with treatment‐refractory rheumatoid arthritis (RA).Methods. Twenty patients with active RA were recruited. Ten patients received IVIg and 10 received albumin. Study subjects were given 6 courses of either IVIg (5 mg/kg) or albumin (5 mg/kg), once every 3 weeks. Baseline medications were continued and not changed throughout the study.Results. There were no complications. Five patients dropped out before the 18‐week followup visit. No significant differences between treatment groups were noted during the 18‐week trial in terms of global activity indices (patient or physician assessment), joint swelling, joint pain or tenderness, erythrocyte sedimentation rate, C‐reactive protein level, or rheumatoid factor. The protocol was terminated prematurely because of reported contamination of IVIg by hepatitis C virus. None of the patients showed evidence of hepatitis C infection by serologic analysis or by polymerase chain reaction.Conclusion. Low‐dose IVIg, as administered in this trial, does not show a therapeutic effect in patients with refractory RA.
A double‐blind, placebo‐controlled study of anti‐CD5 immunoconjugate in patients with rheumatoid arthritis
Authors: Olsen Nancy J. , Brooks Raye H. , Cush John J. , Lipsky Peter E. , St. Clair E. William , Matteson Eric L. , Gold Kenneth N. , Cannon Grant W. , Jackson Christopher G. , McCune W. Joseph , Nelson Betty , Lorenz Todd , Strand Vibeke 
Published: February 2007

AbstractObjective. To evaluate the efficacy of an anti‐CD5 ricin‐linked immunoconjugate (CD5‐IC) in patients with rheumatoid arthritis (RA).Methods. A total of 104 evaluable patients were enrolled in a multicenter, double‐blind, multiple‐dose, placebo‐controlled study of CD5‐IC.Results. Treatment with CD5‐IC in doses up to 8 mg/m2/day for 4 days in 1 month failed to produce marked or prolonged T cell depletion and was no more effective than placebo in ameliorating disease manifestations. An unexpectedly high placebo response was observed in 48% of the patients. Adverse events were correlated with the dose of CD5‐IC, but the treatment was generally well‐tolerated.Conclusion. At the doses used in this study, CD5‐IC was ineffective for treating RA.
Clinical features and therapeutic management of subglottic stenosis in patients with Wegener's granulomatosis
Authors: Langford Carol A. , Sneller Michael C. , Hallahan Claire W. , Hoffman Gary S. , Kammerer William A. , Talar‐Williams Cheryl , Fauci Anthony S. , Lebovics Robert S. 
Published: February 2007

AbstractObjective. To determine the clinical features and optimal treatment of subglottic stenosis (SGS) in patients with Wegener's granulomatosis (WG).Methods. Review of 43 patients with SGS and treatment of 20 patients with intratracheal dilation—glucocorticoid injection therapy.Results. SGS developed in 43 of 189 patients with WG who were followed up at the National Institutes of Health Clinical Center. The diagnosis of SGS occurred in the absence of other features of active WG in 21 of 43 patients (49%). In 21 patients (49%), SGS began while the patient was receiving systemic immunosuppressive therapy for disease activity involving other sites. Tracheostomy was required in 10 of 18 patients (56%) who were treated with systemic immunosuppressive therapy. In 20 patients treated with intratracheal therapy, none required tracheostomy and 6 with previous tracheostomies were decannulated.Conclusion. SGS often occurs independently of other features of active WG and is frequently unresponsive to systemic immunosuppressive therapy. Intratracheal dilation—injection therapy provides a safe and effective treatment for WG‐associated SGS and, in the absence of major organ disease activity, should be used without concomitant systemic immunosuppressive agents.
Presence of antibodies to native G1 domain of aggrecan core protein in synovial fluids from patients with various joint diseases
Authors: Karopoulos Christopher , Rowley Merrill J. , Ilic Mirna Z. , Handley Christopher J. 
Published: February 2007

AbstractObjective. To investigate the occurrence of IgG antibodies to aggrecan in synovial fluids (SF) from patients with arthritis and various articular diseases, and to determine the nature of epitopes present within aggrecan that react with these antibodies.Methods. SF samples were reacted with native aggrecan, reduced and alkylated aggrecan, chondroitin sulfate, and keratan sulfate, using dot‐blots and a novel enzyme‐linked immunosorbent assay (ELISA). The nature of the epitopes present on aggrecan was elucidated using Western blots and a competitive inhibition ELISA.Results. IgG antibodies to aggrecan were found in >50% of the SF samples tested. No IgG antibody reactivity was observed in serum from the same patients. The antibodies appeared to react predominantly with native aggrecan, and there was no disease specificity. It was shown that the epitopes to these antibodies were located within the N‐terminal region of the core protein.Conclusion. This study demonstrates the frequent occurrence of IgG antibodies to aggrecan in human SF. The major epitope is located in the G1 domain of the aggrecan core protein. These IgG antibodies appear to be produced locally within the synovial cavity, probably in response to various articular diseases, resulting in the loss of native aggrecan from articular cartilage.
A randomized, double‐blind study comparing twenty‐four‐week treatment with recombinant interferon‐γ versus placebo in the treatment of rheumatoid arthritis
Authors: Veys Eric M. , Menkes Charles‐Joël , Emery Paul 
Published: February 2007

AbstractObjective. To evaluate the safety and efficacy of recombinant interferon‐γ (rIFNγ) in patients with active rheumatoid arthritis (RA), using an induction and maintenance regimen.Methods. A multicenter, randomized, double‐blind trial of 197 patients with RA was conducted to compare the effects in a group receiving 50 μg of rIFNγ, given subcutaneously in a decreasing regimen over 24 weeks, with those in a placebo group receiving injections of placebo at the same time frequency. Standard clinical assessments were performed.Results. Both rIFNγ and placebo produced a significant improvement from baseline to end point visit for most measurements (except erythrocyte sedimentation rate, duration of morning stiffness, and grip strength), but no significant intergroup differences were seen. Regarding adverse effects, mild local skin reactions at the site of injection were observed, and among the cardiovascular events, mild edema and vasodilatation were reported.Conclusion. IFNγ proved no more effective than placebo in this group of patients with RA. IFNγ was well tolerated in this group of patients, without increased toxicity compared with placebo.
Rheumatoid arthritis synovial fibroblast and U937 macrophage/monocyte cell line interaction in cartilage degradation
Authors: Scott Boyd B. , Weisbrot Lisa M. , Greenwood Janice D. , Bogoch Earl R. , Paige Christopher J. , Keystone Edward C. 
Published: February 2007

AbstractObjective. To examine the interaction between synovial fibroblasts and macrophages in the context of cartilage degradation.Methods. An in vitro model of human cartilage degradation was used, in which purified populations of fibroblasts and macrophages were added to a radio‐labeled cartilage disc. Cartilage destruction was measured by the percentage of radiolabel release.Results. Fibroblasts, obtained from either rheumatoid arthritis (RA) or osteoarthritis synovial tissue, could mediate cartilage degradation if cocultured with the U937 macrophage cell line. Skin and RA bone marrow fibroblasts had no degradative effect on cartilage. Fibroblast—macrophage contact was not required for cartilage degradation. Cartilage degradation by synovial fibroblasts was inhibited by antibodies to tumor necrosis factor α (TNFα), interleukin‐1β (IL‐1β), and IL‐6. Cartilage degradation was almost completely abrogated by a combination of antibodies to TNFα and IL‐1β. Contact between fibroblasts and cartilage was shown to be essential. Antibodies to CD44, but not to intercellular adhesion molecule 1, markedly inhibited cartilage degradation.Conclusion. TNFα, IL‐1β, and IL‐6 were involved in the activation of synovial fibroblasts to cause cartilage degradation. Cartilage degradation occurred only when fibroblasts were in contact with cartilage. CD44 was demonstrated to be involved in the fibroblast—cartilage interaction.
Cr1, CD35 IN synovial fluid from patients with inflammatory joint diseases
Authors: Sadallah Salima , Lach Estelle , Lutz Hans U. , Schwarz Sibylle , Guerne Pierre‐André , Schifferli Jürg A. 
Published: February 2007

AbstractObjective. To investigate synovial fluid (SF) for the presence of CR1 and to study its relationship to SF leukocytes and to serum levels of soluble CR1 (sCR1) in patients with rheumatic diseases.Methods. Synovial fluids were collected from 35 patients with rheumatoid arthritis (RA) and 26 patients with other inflammatory joint diseases. Total CR1 in the SF and serum were measured with a sandwich enzyme‐linked immunosorbent assay (ELISA) that recognized both soluble and transmembrane forms of CR1. The characteristics of CR1 in SF were analyzed by ultracen‐trifugation and by a second ELISA specific for trans‐membrane CR1.Results. CR1 was found in all SF samples tested (range 5‐281 ng/ml). SF CR1 was higher in patients with RA (mean ± SD 81 ± 66 ng/ml) than in those with other inflammatory joint diseases (31.8 ± 23.8 ng/ml) (P < 0.001). Serum sCR1 was not significantly increased in the patients compared with the normal subjects. There was no correlation between serum sCR1 and SF CR1. In 44% of the patients, the SF CR1 level was higher than the serum sCR1 level. A fraction (30–80%) of SF CR1 was pelleted by ultracentrifugation and, unlike serum sCR1, it reacted in an ELISA specific for transmembrane CR1. Thus, SF contained 2 forms of CR1: a membrane‐associated and a soluble form, which was confirmed by sucrose density‐gradient ultracentrifugation. SF CR1 levels correlated directly with the number of SF total leukocytes and polymorphonuclear leukocytes (PMN). These 2 forms of CR1 were also found in the supernatant of in vitro—activated PMN from normal subjects. SF CR1 exhibited the capacity to act as a cofactor for the factor I degradation of C3b.Conclusion. CR1 is found in the SF of patients with joint inflammation. The data suggest that SF CR1 originates from the infiltrating leukocytes, which shed both a soluble and a membrane‐associated form. Whether SF CR1 participates in the local regulation of complement activation remains to be examined.
Elevated cytokine messenger RNA levels in the peripheral blood of patients with rheumatoid arthritis suggest different degrees of myeloid cell activation
Authors: Schulze‐Koops Hendrik , Davis Laurie S. , Kavanaugh Arthur F. , Lipsky Peter E. 
Published: February 2007

AbstractObjective. To determine whether monocytes in rheumatoid arthritis (RA) are activated to produce proinflammatory cytokines in the peripheral circulation before entering the synovium and whether the pattern of cytokines that is expressed correlates with disease activity.Methods. Cytokine messenger RNA (mRNA) levels were assessed in peripheral blood mononuclear cells (PBMC) from 14 RA patients and 14 healthy controls by semiquantitative reverse transcription–polymerase chain reaction technology. The method employed was sufficiently sensitive to assess cytokine mRNA levels in freshly isolated cells without the necessity of in vitro stimulation. Thus, an estimate of the in vivo state of activation could be obtained.Results. Interleukin‐8 (IL‐8) mRNA levels were elevated in all 14 RA patients compared with normal controls, whereas 7 of 14 RA patients had elevated levels of mRNA for IL‐6 or IL‐10. IL‐1B mRNA levels were below the normal range in 3 of 14 patients, within normal limits in 4 of 14, and elevated in 7 of 14. Tumor necrosis factor a mRNA levels were within the normal range in 9 of 14 patients and below normal in 5 of 14. There was a statistically significant difference between the mean IL‐10 (P < 0.05) and IL‐8 (P < 0.001) mRNA.levels in RA patients and normal controls. Of note, the 7 patients with elevated IL‐lβ mRNA levels also expressed the highest levels of IL‐8 mRNA. Whereas a strong correlation between the expression of IL‐lβ and IL‐8 mRNA (P < 0.001) was found, expression of all other mRNA occurred independently of each other. Levels of cyclooxygenase 2 (COX‐2) mRNA were also determined to evaluate the status of myeloid cell activation more completely. COX‐2 mRNA levels were within the normal range in 4 of 11 patients and below normal in 7 of 11, but did not correlate with the expression of any of the cytokine mRNA.Conclusion. Elevated levels of mRNA for selected cytokines that are predominantly produced by monocytes can be found in the PBMC of many RA patients. The data indicate that myeloid precursor cells become activated to produce cytokines before they enter the synovium, a finding which emphasizes the systemic nature of RA.
Induction of alternative splicing of HLA‐B27 by bacterial invasion
Authors: Huang Feng , Yamaguchi Akihiro , Tsuchiya Naoyuki , Ikawa Takashi , Tamura Naoto , Virtala Mika M. K. , Granfors Kaisa , Yasaei Parvin , Yu David Tak Yan 
Published: February 2007

AbstractObjective. Alternative splicing of certain class I major histocompatibility complex pre–messenger RNA (pre‐mRNA) is known to lead to generation of a cell‐free soluble protein analog. This study was undertaken to examine whether this process occurs with HLA–B27, whether the process is modified by arthritis‐causing bacteria, and whether the assembly of the soluble molecules follows the same pathway as the integral parent molecules.Methods. Alternative splicing of pre‐mRNA was analyzed by reverse transcriptase‐polymerase chain reaction, and assembly of soluble HLA–B27 by immunoprecipitation followed by sodium dodecyl sulfatepolyacrylamide gel electrophoresis and autoradiography.Results. There was alternative splicing of the pre‐mRNA of HLA–B27. The process could be amplified by invasion with Salmonella or Yersinia bacteria. The soluble HLA–B27 was assembled in a pathway similar to that of the parent molecule.Conclusion. The association between arthritiscausing bacteria and HLA–B27 positive cells is a complex event. Soluble HLA–B27 is a potential key player.
In vivo direct gene transfer into articular cartilage by intraarticular injection mediated by HVJ (Sendai virus) and liposomes
Authors: Tomita Tetsuya , Hashimoto Hideo , Tomita Naruya , Morishita Ryuichi , Lee Seung Bak , Hayashida Kenji , Nakamura Norimasa , Yonenobu Kazuo , Kaneda Yasufumi , Ochi Takahiro 
Published: February 2007

AbstractObjective. To establish a system for efficient, direct in vivo gene transfer into joints.Methods. A hemagglutinating virus of Japan (HVJ; Sendai virus)‐liposome suspension containing SV40 large T antigen (SVT) gene was injected intraarticularly into knee joints of 6‐week‐old female Lewis rats. Rats were killed at various times for immunohistochemical analysis of the expression of SVT gene.Results. The expression of SVT gene was detected immunohistochemically in chondrocytes in the superficial and middle zones of articular cartilage in the knee joints. The average percentage of SVT‐positive cells was estimated to be ∼30% on days 3, 7, 14, and 21 after transfection. Moreover, no pathologic change caused by HVJ‐liposome injection was observed in the joints.Conclusion. The transfection frequency and stability of expression recognized in this study indicate the possibility of a strategy for treatment of joint disorders, including arthritis, using direct gene transfer.