bluuebunny/crossref_metadata_2025_split huggingface dataset:
Corticosteroids plus pulse cyclophosphamide and plasma exchanges versus corticosteroids plus pulse cyclophosphamide alone in the treatment of polyarteritis nodosa and churg‐strauss syndrome patients with factors predicting poor prognosis
Authors: Guillevin Loïc , Lhote François , Cohen Pascal , Jarrousse Bernard , Lortholary Olivier , Généreau Thierry , Léon Anne , Bussel Annette 
Published: February 2007

AbstractObjective. To define the most effective treatment for severe polyarteritis nodosa (PAN) and Churg‐Strauss syndrome (CSS) and to investigate the indication for plasma exchange treatment.Methods. We conducted a prospective, randomized, multicenter trial in which 62 patients were randomly assigned to receive either prednisone plus cyclophosphamide (intravenous bolus) (group An = 28) or prednisone plus cyclophosphamide (intravenous bolus) plus plasma exchanges (group B; n = 34) as first‐line treatment for severe PAN or CSS. Factors predicting poor prognosis were renal symptoms, gastrointestinal tract involvement, cardiomyopathy, central nervous system involvement, weight loss > 10% of body weight, and age > 50 years old. Patients with hepatitis B virus‐related PAN were not included in this study. The end point of the study was control of the disease (recovery or remission) or death.Results. Clinical symptoms and laboratory findings did not differ significantly in the 2 groups. Initial control of the disease was similar in both groups. Relapse after initial control of the disease was observed in 7 patients (4 in group A and 3 in group B). The mean ± SD followup period was 31.1 ± 20 months for group A and 35.9 ± 16.8 months for group B. At 5 years of followup, 38 patients (61.3%) were cured (16 in group A and 22 in group B), and 5 (8.1%) were in remission without treatment but had not yet completed the curedefining period of 18 months (3 in group A and 2 in group B). Eight (12.9%) (2 in group A and 6 in group B) were considered to be in clinical remission and required a maintenance regimen of low‐dose corticosteroids. Eleven patients died during the study period (7 in group A [25%], 4 in group B [11.8%]). Uncontrolled vasculitis was responsible for 4 deaths (2 in each group), and treatment side effects caused the death of 1 patient in group A. There was no significant difference between the 5‐year cumulative survival rates of the 2 groups (75% and 88%, respectively).Conclusion. Based on our data, combined treatment with prednisone, cyclophosphamide, and plasma exchanges is not superior to treatment with prednisone and cyclophophamide alone, and plasma exchanges should not be systematically proposed for initial treatment of severe PAN or CSS.
Treatment of calcinosis with diltiazem
Authors: Palmieri Genaro M. A. , Sebes Jeno I. , Aelion Jacob A. , Moinuddin Mohamed , Ray Morris W. , Wood George C. , Leventhal Marvin R. 
Published: February 2007

AbstractObjective. To test the hypothesis that the calcium antagonist diltiazem is effective in the treatment of calcinosis.Methods. Diltiazem, 240–480 mg/day, was given to 4 patients with idiopathic or CREST‐related (calcinosis, Raynaud'S phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias) calcinosis for 1–12 years. Serial radiographs of the affected areas, using identical technique, and clinical evaluations were obtained. A fifth patient, who did not tolerate diltiazem, received verapamil, 120 mg/day for 18 months.Results. All patients taking diltiazem had a reduction or disappearance of the calcific lesions, with striking clinical improvement. One patient'S case was followed for 12 years. The response to diltiazem during the first 5 years of treatment has been previously reported in detail; however, over 7 years of additional treatment, there was further reduction of the lesions. One patient developed a large calcific lesion while receiving verapamil for hypertension, and after verapamil was replaced with diltiazem, there was a dramatic response. Verapamil was ineffective in the fifth patient, who did not tolerate diltiazem.Conclusion. Long‐term treatment with diltiazem, but not verapamil, is effective in calcinosis.
Antibody reactivity to the hres‐1 endogenous retroviral element identifies a subset of patients with systemic lupus erythematosus and overlap syndromes
Authors: Perl Andras , Colombo Emanuela , Dai Huiliang , Agarwal Rajeev , Mark Kenneth A. , Banki Katalin , Poiesz Bernard J. , Phillips Paul E. , Hoch Sallie O. , Reveille John D. , Arnett Frank C. 
Published: February 2007

AbstractObjective. To evaluate the correlation between the presence of antibodies to an endogenous retroviral element–encoded nuclear protein autoantigen, HRES‐1, and the presence of other antinuclear antibodies and HLA class II alleles in patients with systemic lupus erythematosus (SLE) and overlap syndromes.Methods. Antibody reactivities to native and recombinant proteins and synthetic peptides were assessed by counterimmunoelectrophoresis, enzyme‐linked immunosorbent assay, and Western blotting. HLA class II alleles were determined by oligonucleotide typing.Results. Forty‐eight percent of the 153 patients with autoimmune disease, and 52% of the subgroup with SLE, had HRES‐1 antibodies. In contrast, 3.6% of 111 normal donors, and none of 42 patients with the acquired immunodeficiency syndrome or 50 asymptomatic human immunodeficiency virus 1–infected patients, had HRES‐1 antibodies. Chi‐square analyses revealed a significant association between anti–HRES‐1 and anti‐RNP and an inverse correlation between HRES‐1 and Ro/La autoantibodies in patients with SLE or overlap syndromes. Antigenic epitopes of HRES‐1 and the retroviral gag–related region of the 70‐kd protein component of U1 small nuclear RNP, which share 3 consecutive highly charged amino acids (Arg‐Arg‐Glu), an additional Arg, and functionally similar Arg/Lys residues, represent cross‐reactive epitopes between the two proteins. Selective removal of HRES‐1 antibodies from sera of HRES‐1‐seropositive/RNP‐seropositive patients by absorption on recombinant HRES‐1/glutathione‐S‐transferase‐conjugated agarose beads had no effect on anti‐RNP reactivities. A comparative multivariate analysis of HLA class II genes revealed a differential segregation of DQB1 alleles in HRES‐1‐seropositive versus HRES‐1‐seronegative patients (P = 0.04). While a relative increase of DQB1*0402 among HRES‐1‐seropositive patients was noted across ethnic groups (P = 0.02), a decrease of DQB1*0201 and DQB1*0301 was found in white HRES‐1‐seropositive patients (P = 0.04).Conclusion. Autoantibodies to HRES‐1 are detectable in a distinct subset of patients with autoimmune disease, primarily in those who do not have antibodies to Ro and La. Anti–HRES‐1 and anti‐RNP reactivities are mediated by cross‐reactive but separate antibody molecules. HLA–DQB genes, rather than HLA–DRB or DQA genes, may have a more significant influence on generation of these antinuclear autoantibodies.
Association of hla‐b39 with hla‐b27‐negative ankylosing spondylitis and pauciarticular juvenile rheumatoid arthritis in japanese patients
Authors: Yamaguchi Akihiro , Tsuchiya Naoyuki , Mitsui Hiroshi , Shiota Michiko , Ogawa Atsuko , Tokunaga Katsushi , Yoshinoya Sadayoshi , Juji Takeo , Ito Koji 
Published: February 2007

AbstractObjective. To investigate the characteristics of HLA‐B27 that render susceptibility to seronegative spondylarthropathies.Methods. Serologic HLA class I typing of Japanese patients with ankylosing spondylitis (AS), juvenile rheumatoid arthritis (JRA), and healthy controls, was performed. HLA‐B39 subtypes were determined by polymerase chain reaction‐sequence‐specific oligohy‐bridization.Results. HLA‐B27 was present in 40 of 48 patients with AS (83%), and in only 1 of 210 healthy controls (0.5%). Three of 8 patients (37.5%) who were negative for HLA‐B27 were positive for HLA‐B39, which was significantly higher compared with the HLA‐B27‐negative controls (6.2% P = 0.01). Significant association with HLA‐B39 was also noted in the JRA patients (16.7%; P < 0.01), especially in those patients with pauciarticular‐onset disease (33.3%; P < 0.01). Ten of 13 HLA‐B39‐positive patients had subtype B*3901 and 3 had B*3902.Conclusion. Because HLA‐B27 and HLA‐B39 share Glu at position 45 and Cys at position 67, both of which constitute components of the peptide‐anchoring B pocket, and because they possess similar peptide‐ligand motifs, our results may support either the role of the peptides presented by class I antigens or the importance of Cys at position 67, in the development of spondylarthropathies and pauciarticular‐onset JRA.
Rheumatoid synovial fibroblast adhesion to human articular cartilage
Authors: Mccurdy Lewis , Winn Chatham W. , Blackburn Warren D. 
Published: February 2007

AbstractObjective. To determine if preexposure of human articular cartilage to activated neutrophils alters rheumatoid synovial fibroblast adhesion to human articular cartilage.Methods. Human articular cartilage was exposed to either activated neutrophils, interleukin‐1, or supernatants obtained from activated neutrophils that had been treated with different protease inhibitors. Radiolabeled rheumatoid synovial fibroblasts were then incubated with the cartilage and the number of counts associated with the cartilage was determined.Results. Pretreatment of human articular cartilage with either activated neutrophils or supernatants obtained from activated neutrophils enhanced subsequent rheumatoid synovial fibroblast adhesion. In contrast, interleukin‐1 treatment of cartilage did not alter the adhesion of synovial fibroblasts. The enhanced adhesion could be attenuated by pretreatment of the neutrophil supernatants with either diisopropylfluoro‐phosphonate or EGTA and almost completely abolished by using both inhibitors.Conclusion. This study demonstrates that adhesion of rheumatoid synovial fibroblasts to human articular cartilage can be enhanced by exposing the cartilage to proteases released by neutrophils. These results suggest that neutrophil products may play a role in enhancing adhesion of rheumatoid synovium to cartilage in vivo.
A reexamination of the relationship between active rheumatoid arthritis and the acquired immunodeficiency syndrome
Authors: Ornstein Matthew H. , Kerr Leslie Dubin , Spiera Harry 
Published: February 2007

AbstractThree patients with rheumatoid arthritis (RA) that remitted with the development of the human immunodeficiency virus (HIV) infection have been described in the literature, and this has contributed to the belief that RA and HIV infection or the acquired immunodeficiency syndrome (AIDS) cannot coexist. However, a computerized MEDLINE literature search revealed reports of 4 patients who did have active RA and AIDS or HIV infection, as well as other case reports of symmetric polyarthritis compatible with RA in patients with HIV infection. Each of the patients whose RA remitted had received standard disease‐modifying antirheumatic drug therapy, and 1 of the 3 had a normal T helper: T suppressor ratio at the time of remission. Of the 4 previously reported patients with active RA and AIDS or HIV infection, all had decreased numbers of T helper lymphocytes. The present report describes a fifth patient with both RA and AIDS and reviews the data concerning the coexistence of these 2 diseases. It appears that active RA may indeed coexist with AIDS. It remains to be seen under what settings HIV may have a diseasemodifying effect in RA. These issues have important implications regarding the pathogenesis and therapy of RA, especially in terms of the role of CD4+ lymphocytes and anti‐CD4 monoclonal antibody therapy.
Levels of soluble fas/APO‐1 /CD95 in systemic lupus erythematosus and juvenile rheumatoid arthritis
Authors: Knipping Eckart , Krammer Peter H. , Onel Karen B. , Lehman Thomas J. A. , Mysler Eduardo , Elkon Keith B. 
Published: February 2007

AbstractObjective. To quantify soluble Fas/APO‐1 (sFas/APO‐1 ) protein in the serum of patients with systemic lupus erythematosus (SLE) and juvenile rheumatoid arthritis (JRA).Methods. Soluble Fas/APO‐1 was quantified using a sandwich enzyme‐linked immunosorbent assay. Disease activity in SLE patients was assessed by the SLE Disease Activity Index.Results. Increased serum sFas/APO‐1 levels were observed in only 1 of the 27 SLE patients (4%) and 3 of the 10 JRA patients (30%).Conclusion. Increased levels of sFas/APO‐1 occurred infrequently in SLE, and the levels were lower than 10 ng/ml. Increased levels of sFas/APO‐1 are not specific for SLE. Soluble Fas/APO‐1 is unlikely to be of major pathogenetic significance in SLE.
Lack of correlation between serum soluble fas/APO‐1 levels and autoimmune disease
Authors: Goel Niti , William Clair E. S. T. , Fleming Judith A. , Ulrich Dawn T. , Lynch David H. , Seldin Michael F. 
Published: February 2007

AbstractObjective. To determine whether elevated soluble Fas/APO‐1 (sFas/APO‐1 ) levels are associated with either autoimmune disease or evidence of flares in autoimmune disease.Methods. Thirty‐seven serum samples were retrospectively obtained from normal controls and patients with laboratory evidence of autoimmune disease activity. These samples were assayed for sFas/APO‐1 levels by an enzyme‐linked immunosorbent assay, and hospital medical records were retrospectively reviewed for clinical and laboratory characteristics of the patients.Results. Soluble Fas/APO‐1 levels did not correlate with clinical diagnoses or laboratory abnormalities. The mean and range of sFas/APO‐1 levels were similar in systemic lupus erythematosus patients (including those with active disease), patients with other autoimmune diseases, and normal controls.Conclusion. These data strongly suggest that measurement of sFas/APO‐1 levels is unlikely to hold clinical value or play a role in the pathogenesis of autoimmune disease.
Negatively charged residues interacting with the p4 pocket confer binding specificity to DRB1*0401
Authors: Woulfe Susan L. , Bono Christine P. , Zacheis Michelle L. , Kirschmann Dawn A. , Baudino Troy A. , Swearingen Craig , Karr Robert W. , Schwartz Benjamin D. 
Published: February 2007

AbstractObjective. To identify critical residues involved in the binding of a selective peptide to DRB1*0401.Methods. The binding of peptides to native or site‐directed mutant DR molecules was evaluated using enzyme‐linked immunosorbent assay and flow cytometry.Results. Amino acid substitutions at DR and peptide residues, which were predicted to contribute to interactions within the DR p4 pocket, had the greatest effects on the specificity of binding.Conclusion. Differences in the peptide‐binding repertoires of DR molecules may contribute to associations with autoimmune diseases.
The genotypic distribution of shared‐epitope DRB1 alleles suggests a recessive mode of inheritance of the rheumatoid arthritis disease‐susceptibility gene
Authors: Evans Toni I. , Han Jinfeng , Singh Rovinder , Moxley George 
Published: February 2007

AbstractObjective. To test whether the genotypic distribution of rheumatoid arthritis (RA)–associated DRB1 alleles suggests that the DRB1‐a ssociated disease‐susceptibility gene has a recessive or additive (dominant) mode of inheritance.Methods. Caucasian patients with RA and control subjects were recruited from a faculty outpatient practice. DRB1 typing was done by several DNA‐based techniques: polymerase chain reaction (PCR), followed by dot‐blot hybridization with sequence‐specific oligonucleotides, conventional and PCR‐based restriction fragment length polymorphisms (RFLPs), and a multiplex amplification–refractory mutation RFLP system. The genotypic distribution of shared‐epitope DRB1 alleles was analyzed by antigen genotype frequency among patients. The analytical method postulates a linkage‐disequilibrium model with a disease locus close to a marker locus and a marker allele in linkage disequilibrium with the disease‐susceptibility allele. In this instance, the marker allele was defined alternatively by any DR4‐g roup allele, by any DR4‐g roup or DR1‐g roup allele, by any DR4‐g roup shared‐epitope allele, by any DRC‐group shared‐epitope allele plus DRB1*0101, or by any shared‐epitope DRB1 allele. Observed numbers were compared with those predicted for recessive mode or additive (dominant) mode of inheritance of the DRB1‐a ssociated RA disease‐susceptibility gene.Results. The genotypic distribution of shared‐epitope DRB1 alleles (DRB1*0401, *0404, *0405, *0408, *0101, *0102, or *1001) fit that predicted for a recessive mode of inheritance and was significantly different from that predicted for an additive (dominant) mode. When the analysis was restricted to shared‐epitope DR4 alleles alone (DRB1*0401, *0404, *0405, or *0408), the observed genotype numbers fit the recessive mode best. When DR1‐g roup alleles were added to DR4‐g roup alleles, or alternatively, when the major shared‐epitope DR1 allele (*0101) was added to DR4‐g roup shared‐epitope alleles, there was a less significant deviation from the additive mode of inheritance. The reason for this was derived by comparison of observed genotype frequencies to those expected under Hardy‐Weinberg equilibrium; there was a deficit of persons with DRB1*0401,*0101 and an excess of *0101,X.Conclusion. The genotypic distribution of shared‐epitope DRB1 marker alleles suggests that the mode of inheritance of the DRB1‐a ssociated disease susceptibility gene must be recessive and not additive (dominant).
Nuclear factor–kB in rheumatoid synovium. Localization of P50 and P65
Authors: Handel Malcolm L. , Mcmorrow Linda B. , Gravallese Ellen M. 
Published: February 2007

AbstractObjective. To identify the cells that express transcription factor NF‐kB subunits p50 and p65 in synovial tissue from patients with rheumatoid arthritis (RA) and to correlate the distribution of p50 and p65 with CD14 (macrophage lipopolysaccharide receptor) and members of the AP‐1 transcription factor family, Jun and Fos.Methods. Immunohistochemistry was used to identify p50, p65, Jun and Fos in sections of synovial tissue from 13 patients with RA and 4 ‘normal’ control subjects. Double staining for CD14 and each of the transcription factor subunits was performed.Results. Subunits p50 and p65 were present in the nuclei of synovial cells in all 13 RA patients, with expression varying from rare cells to more than half of all cells. In most cases, nuclear p50 and p65 were present in approximately one‐third of synovial lining cells and in a variable proportion of cells scattered throughout the sublining region, including the endothelium. The distributions of p50 and p65 were similar. Jun and Fos were present in the nuclei of a large proportion of synovial lining cells with significantly less expression elsewhere. In each case the Jun/Fos distribution was clearly different from the p50/p65 distribution, although there was significant overlap in many cases. Cells expressing CD14 were mostly Jun/Fos negative and were predominantly p50/p65 positive. There was negligible staining for p50 or p65 in the 4 normal control synovium samples.Conclusion. In most RA patients, the p50 and p65 subunits of NF‐kB were present in the majority of CD14‐p ositive cells within the lining and sublining regions and in a proportion of other cells throughout the synovium, including endothelial cells. NF‐kB is likely to play an important role in the expression of macrophage‐derived cytokines in rheumatoid synovium. Different but overlapping distributions of nuclear p50 and p65 versus Jun and Fos indicate separate or divergent mechanisms for the activation of NF‐kB and the expression of AP‐1 proteins in rheumatoid synovium.
Terminal differentiation of spontaneous rheumatoid factor–secreting B cells from rheumatoid arthritis patients depends on endogenous interleukin‐1 0
Authors: Perez Lisardo , Orte Javier , A. Brieva José 
Published: February 2007

AbstractObjective. The presence of serum rheumatoid factor (RF) and spontaneous RF‐secreting B cells is a common feature in most patients with rheumatoid arthritis (RA). This study analyzed the cytokine(s) that controls the final maturation of B cells capable of spontaneous IgM‐RF secretion in vitro.Methods. RA patients' peripheral blood mononuclear cells (PBMC), as well as adherent and nonadherent cell fractions, were cultured, and spontaneous IgM‐RF and interleukin‐1 0 (IL‐1 0) secretion were determined by enzyme‐linked immunosorbent assay.Results. The RF+ RA PBMC, but not PBMC from RF– RA patients or healthy controls, actively produced IgM‐RF in a linear manner for 14 days. This activity depended on the presence of fetal calf serum and did not require cellular DNA synthesis. Spontaneous IgM‐RF secretion depended on IL‐1 0, as deduced from the following findings: 1) IL‐1 0, but not a variety of cytokines including IL‐6, restored missing IgM‐RF secretion by PBMC in serum‐free supplemented cultures; 2) the addition of anti–IL‐1 0, but not anti–IL‐6, blocking antibodies inhibited PBMC IgM‐RF secretion, and this effect could be reversed by exogenous IL‐1 0; and 3) RA PBMC actively produced IL‐1 0 in vitro. The cells responsible for endogenous IL‐1 0 production were found in the adherent cell fraction. Finally, IL‐1 0 induced IgM‐RF, but not total IgM, secretion by RA PBMC.Conclusion. In patients with RA, circulating B cells capable of spontaneous IgM‐RF secretion require IL‐1 0 production by adherent cells to reach terminal maturation.
Long‐term amelioration of rat adjuvant arthritis following systemic elimination of macrophages by clodronate‐containing liposomes
Authors: Kinne Raimund W. , Schmidt‐Weber Carsten B. , Hoppe Ralph , Buchner Eberhard , Palombo‐Kinne Ernesta , Nürnberg Eberhard , Emmrich Frank 
Published: February 2007

AbstractObjective. To determine whether systemic elimination of macrophages by means of clodronate‐containing liposomes counteracts inflammation and joint destruction in rats with established adjuvant arthritis (AA).Methods. Rats with AA received a total of 2.7 mg of clodronate encapsulated in liposomes in 3 intravenous doses on days 10, 11, and 12 of arthritis. Phosphate buffered saline (PBS), PBS‐laden liposomes, or free clodronate were used as negative controls. Clinical, hematologic, and histopathologic signs of AA were monitored, and depletion of macrophages by clodronate‐liposomes was evaluated both in the synovial membrane (SM) and in organs of the mononuclear phagocyte system (MPS).Results. Clodronate‐laden liposomes led to significant, long‐term amelioration of the clinical signs of AA, a reduction in the erythrocyte sedimentation rate (ESR), and counteraction of joint destruction, not only immediately after treatment, but also for 2 weeks thereafter. Free clodronate induced moderate clinical improvement and a significant decrease in the ESR, but only during the late phase of AA. Drug‐free vesicles even aggravated the joint destruction. Clodronate‐laden liposomes did not induce significant depletion of resident macrophages in the SM, but rather, in the paracortical region of popliteal lymph nodes, in the liver, and in the marginal zone and periarteriolar lymphatic sheaths of the spleen.Conclusion. Clodronate‐laden liposomes induce long‐term amelioration of AA, even if administered for a brief period during the florid phase of the disease. The amelioration is paralleled by the elimination of macrophages in immunocompetent areas of the spleen and draining lymph nodes, but not locally in the SM. This suggests an influence of the treatment on the immunoregulatory rather than effector, functions of macrophages.