bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absence of Lentiviral and Human T Cell Leukemia Viral Sequences in Patients with Rheumatoid Arthritis
Authors: Giovine Francesco S. Di , Bailly Sabine , Bootman Janet , Almond Neil , Duff Gordon W. 
Published: February 2007

AbstractObjective. The etiology of rheumatoid arthritis (RA) is unknown, and the possibility that an infectious agent is involved has not been excluded. Lentiviruses can cause chronic arthritis in humans and in animals and have been suggested as candidate agents in RA. We therefore tested for the presence of lentiviruses and also for human T cell leukemia virus type I (HTLV‐I)/ HTLV‐II in cells from patients with RA.Methods. We used the polymerase chain reaction with degenerate primers designed to recognize highly conserved nucleotide sequences from 5 different pathogenic lentiviruses. This method allowed the detection of at least 1 infected cell/20,000 uninfected cells in control experiments.Results. Testing of synovial cells and blood cells from patients with early RA and patients with established RA did not yield any specific viral product.Conclusion. Our results do not support the presence of lentiviruses or HTLV‐like sequences in RA.
The Time‐Dependence of Long‐Term Prediction in Lupus Nephritis
Authors: Esdaile John M. , Abrahamowicz Michal , Mackenzie Todd , Hayslett John P. , Kashgarian Michael 
Published: February 2007

AbstractObjective. To assess the clinical, laboratory, and renal biopsy predictors of long‐term outcome in lupus nephritis and to investigate the time‐dependence of these predictors.Methods. Eighty‐seven lupus nephritis patients were studied retrospectively for the outcomes renal failure and fatality due to renal involvement. In addition to a conventional Cox model analysis, a new generalized time‐dependent analytic approach was developed and used to assess the time‐dependence of a predictor variable's importance.Results. The mean followup time was 11.9 years. Renal failure (n = 19) was significantly predicted by measures of renal function (abnormal serum creatinine levels, proteinuria, duration of prior renal disease) and immunologic activity (elevated DNA binding, hypocomplementemia, and thrombocytopenia), by overall lupus disease activity measures (le Riche index, Lupus Activity Criteria Count), and by the activity index, the tubulointerstitial index, and the amount of subepithelial deposits on renal biopsy. In general, the laboratory predictors were significantly better prognostic markers in the early years after biopsy, the disease activity measures were best in the later years, and the biopsy variables were significant predictors over the entire observation period. In contrast to the renal failure outcome, the best predictors for death not directly related to lupus nephritis (n = 17) were the extent of comorbid diseases (principally vascular diseases), older age, and the chronicity index. All three predicted well over the extended observation period.Conclusion. The major predictor variables for renal outcomes and nonrenal outcomes are distinct. The time‐dependence of the predictive ability of some variables may be important in managing individual patients. The new generalized time‐dependent analytic technique may have widespread application in studies to identify prognostic factors for established disease or risk factors for the development of disease.
Lymphocyte Antigens in Neuropsychiatric Systemic Lupus Erythematosus
Authors: Denburg Susan D. , Behmann Sharon A. , Carbotte Ramona M. , Denburg Judah A. 
Published: February 2007

AbstractObjective. To examine the relationships among specific lymphocyte antigenic reactivities of lupus sera and central nervous system complications of systemic lupus erythematosus (SLE), lymphocytotoxic antibody (LCA) positivity, and specific cognitive impairment.Methods. Sera from 115 patients with SLE were examined for the presence of IgM‐ and IgG‐class auto‐antibodies binding to surface target antigens on lymphocytes, by immunoblotting and microdroplet lymphocytotoxicity studies. Seventy‐three of these patients also underwent detailed neuropsychological testing within the same time period.Results. Significant associations were found between reactivities to several lymphocyte antigenic moieties and neuropsychiatric SLE (NPSLE) or cognitive impairment. Specifically, immunoblot reactivities to 31–32‐kd, 50–52‐kd, 54–56‐kd, and 97–98‐kd targets were associated with clinical NPSLE; there was a significant association between reactivity to the 50–52‐kd moiety in particular and cognitive impairment. There were also associations between LCA and immunoblot reactivity. Furthermore, the previously reported association between LCA positivity and specific visuospatial cognitive impairment was confirmed with data obtained from 2 different batteries of neuropsychological tests.Conclusion. In some cases, specific antigenic targets of LCA‐containing sera may be implicated in the pathogenesis of NPSLE.
Up‐Regulation of Endothelial Cell Adhesion Molecules Characterizes Disease Activity in Systemic Lupus Erythematosus
Authors: Belmont H. Michael , Buyon Jill , Giorno Ralph , Abramson Steven 
Published: February 2007

AbstractObjective. To test the hypothesis that during exacerbations of systemic lupus erythematosus (SLE), endothelial cells are activated to increase their expression of adhesion molecules.Methods. Endothelial cell expression of E‐selectin, vascular cell adhesion molecule 1 (VCAM‐1), and intercellular adhesion molecule 1 (ICAM‐1) was quantitated immunohistochemically in 20 biopsy specimens from nonlesional, non‐sun‐exposed skin from 16 SLE patients. Disease activity was evaluated with the SLE Disease Activity Index (SLEDAI) and with measurements of complement components C3a desArg, C3, and C4.Results. The mean expression of all 3 adhesion molecules was significantly elevated in patients with SLE versus healthy controls, as well as in patients with active versus inactive SLE. The mean C3a desArg level was significantly higher in patients with active SLE compared with those with inactive SLE. The SLEDAI scores correlated directly with C3a desArg levels and inversely with C3 and with C4 levels. Evaluation of serial biopsy specimens demonstrated loss of endothelial cell adhesion molecules and reduction of C3a levels with clinical improvement.Conclusion. Our findings demonstrate up‐regulation of the surface expression of 3 distinct adhesion molecules, E‐selectin, VCAM‐1, and ICAM‐1, in patients with SLE. The abnormal expression of these endothelial cell adhesion molecules is most marked in patients with active disease characterized by significant elevations of the complement split product C3a desArg. We suggest that in certain SLE patients, excessive complement activation in association with primed endothelial cells induces leukocyte‐endothelial cell adhesion and leuko‐occlusive vasculopathy.
Antihistone Antibodies in Systemic Sclerosis
Authors: Sato Shinichi , Ihn Hironobu , Kikuchi Kanako , Takehara Kazuhiko 
Published: February 2007

AbstractObjective. To determine the prevalence and clinical significance of antihistone antibodies (AHA) in systemic sclerosis (SSc).Methods. Serum samples from patients with limited cutaneous SSc (n = 44), diffuse cutaneous SSc (dcSSc; n = 48), and other SSc‐related disorders (n = 22) were examined by enzyme‐linked immunosorbent assay and immunoblotting for AHA.Results. AHA were demonstrated in 29% of the 92 SSc patients and in 44% of those with dcSSc. The presence of AHA correlated with severe pulmonary fibrosis in those with dcSSc. Immunoblotting revealed that the predominant antigen was histone H1.Conclusion. AHA might be a serologic indicator of the severity of pulmonary fibrosis in SSc.
Treatment of Lupus Interstitial Lung Disease with Intravenous Cyclophosphamide
Authors: Eiser Arnold R. , Shanies Harvey M. 
Published: February 2007

AbstractIntravenous pulse cyclophosphamide (IPC) was used to treat lupus interstitial lung disease in 2 patients. Vital capacity increased by 67–110% of baseline values with IPC treatment. Total lung capacity and diffusing capacity also improved. Dyspnea and other manifestations of lupus improved dramatically. This is the first report documenting the efficacy of the early use of IPC for acute and chronic interstitial lung disease associated with lupus.
Reduced joint counts in controlled clinical trials in rheumatoid arthritis
Authors: Fuchs Howard A. , Pincus Theodore 
Published: February 2007

AbstractResults. The effect sizes of the joint scores derived using a reduced number of joints were similar to those of the original 60‐joint score. The reduced joint count scores revealed significant changes for clinical trials involving as few as 15 patients.Conclusion. Reduced joint count scores may be used to evaluate the results of clinical trials without decreasing the ability to detect change over time. Quantitative assessment of a reduced number of joints may also facilitate assessment of responses to treatment in the routine care of patients with RA.Objective. To determine if quantitative assessment of a reduced number of joints provides information equivalent to that obtained by the traditional 60‐joint evaluation in detecting changes in patients participating in clinical trials of rheumatoid arthritis (RA).Methods. The changes in quantitative joint scores of patients from 3 previously reported clinical trials were compiled and compared with changes in quantitative scores derived using a reduced number of joints. Effect sizes were calculated (mean change in joint score/standard deviation of joint score) and compared for the different joint indices.
The mortality of rheumatoid arthritis
Authors: Wolfe Frederick , Mitchell Donald M. , Sibley John T. , Fries James F. , Bloch Daniel A. , Williams Catherine A. , Spitz Patricia W. , Haga May , Kleinheksel Sue M. , Cathey Mary Ann 
Published: February 2007

AbstractObjective. To determine the risk and causes of death and to quantify mortality predictors in patients with rheumatoid arthritis (RA).Methods. RA patients (n = 3,501) from 4 centers (Saskatoon n = 905, Wichita n = 1,405, Stanford n = 886, and Santa Clara n = 305) were followed for up to 35 years; 922 patients died.Results. The overall standardized mortality ratio (SMR) was 2.26 (Saskatoon 2.24, Wichita 1.98, Stanford 3.08, Santa Clara 2.18) and increased with time. Mortality was strikingly increased for specific causes: infection, lymphoproliferative malignancy, gastroenterologic, and RA. In addition, as an effect of the SMR of 2.26, the expected number of deaths was increased nonspecifically across all causes (except cancer), with a large excess of deaths attributable to cardiovascular and cerebrovascular diseases. Independent predictors of mortality included age, education, male sex, function, rheumatoid factor, nodules, erythrocyte sedimentation rate, joint count, and prednisone use.
Induction of cyclooxygenase ii in human synovial microvessel endothelial cells by interleukin‐1
Authors: Szczepanski Andrew , Moatter Tariq , Carley William W. , Gerritsen Mary E. 
Published: February 2007

AbstractConclusion. IL‐1 treatment of HSE cells induces COX II, as demonstrated by both Northern blotting and immunoprecipitation. The induction of COX II expression provides, at least in part, a mechanism for the pronounced increase in prostanoid synthesis observed in HSE cells following incubation with IL‐1. The selective up‐regulation of HSE COX II by inflammatory cytokines such as IL‐1 suggests that development of specific pharmaceutical inhibitors for this novel isozyme may provide significant new therapeutic advantages in the treatment of RA.Objective. To characterize the effects of inter‐leukin‐1α (IL‐1) on prostanoid biosynthesis by human rheumatoid synovium microvessel endothelium (HSE).Methods. HSE cells were treated with cytokines, metabolic inhibitors, and steroids under various conditions, and prostaglandin biosynthesis was determined by radioimmunoassay. Newly synthesized cyclooxygenase (COX) was quantitated by immunoprecipitation of metabolically labeled HSE cell lysates. The effects of IL‐1 on levels of messenger RNA (mRNA) for COX II were also determined.Results. IL‐1 induced an increase in COX activity (as assessed by prostaglandin E2 release) that was dose‐and time‐dependent and was blocked by cycloheximide, actinomycin D, and dexamethasone. IL‐1 induced a selective increase in COX II mRNA and biosynthesis of COX II protein that was blocked by dexamethasone.Conclusion. Mortality rates are increased at least 2‐fold in RA, and are linked to clinical severity.
Association of tap2 polymorphism with rheumatoid arthritis is secondary to allelic association with hla–drb1
Authors: Marsal Sara , Hall Margaret A. , Panayi Gabriel S. , Lanchbury Jerry S. 
Published: February 2007

AbstractObjective. To study polymorphisms of the newly described TAP2 locus in rheumatoid arthritis (RA) and to analyze their relationship with HLA–DRB1 alleles previously implicated in the development of the disease.Methods. TAP2 polymorphic residues at 3 sites, Val/Ile‐379, Ala/Thr‐565, and Ala/Thr‐665, were characterized by amplification refractory mutation system polymerase chain reaction in 185 RA patients and 48 HLA–DR4 positive healthy controls. HLA‐DR4 subtypes were determined by sequence‐specific priming and oligonucleotide hybridization.Results. The frequencies of Ile‐379, Thr‐565, and Thr‐665 were significantly increased in DR4 positive versus DR4 negative RA patients. TAP2 genotype distributions also differed between the patient groups stratified by DR4 status. However, no significant differences in TAP2 polymorphisms were observed between DR4 positive RA patients and DR4 positive controls, although relationships between specific DR4 subtypes and TAP2 variants were identified.Conclusion. Particular TAP2 polymorphisms are associated with distinct HLA–DR specificities in both normal and RA populations. Thus, the prevalence of specific TAP2 residues and genotypes in RA appears to be secondary to the HLA–DR frequencies and genotypic combinations that are typical of RA.
Hla–drb1 alleles in polymyalgia rheumatica, giant cell arteritis, and rheumatoid arthritis
Authors: Weyand Cornelia M. , Hunder Naomi N. H. , Hicok Kevin C. , Hunder Gene G. , Goronzy Jörg J. 
Published: February 2007

AbstractObjective. Immunogenetic analysis has demonstrated that giant cell arteritis (GCA) and rheumatoid arthritis (RA) are associated with 2 different domains of the HLA–DR4 molecule. The present study was undertaken to evaluate whether polymyalgia rheumatica (PMR) immunogenetically resembles GCA or RA and to determine whether expression of HLA‐DRB1 alleles can be used to detect heterogeneity among PMR patients.Methods. Forty‐six patients with PMR, 52 with GCA, 122 with seropositive RA, and 72 normal individuals were genotyped for HLA‐DRB1 alleles by allele‐specific amplification and subsequent oligonucleotide hybridization.Results. The HLA‐DRB1*04 allele was the most frequent among PMR patients (67%). While the expression of allelic variants of the HLA‐DR4 family was restricted to HLA‐DRB1*0401 and*0404/8 in RA patients, all HLA–DRB1*04 alleles, including B1*0402 and B1*0403, were represented in the PMR group. The distribution of HLA–DRB1 alleles among HLA–DRB1*04 negative patients was similar in those with PMR and those with GCA, and could be distinguished from that in RA patients. In particular, HLA–DRB1*01 alleles, which were found in most HLA–DRB1*04 negative RA patients, were underrepresented in patients with PMR and GCA.Conclusion. The distribution of HLA–DRB1 alleles in PMR resembles that found in GCA. PMR and GCA share the associated sequence polymorphism encoded by the second hypervariable region (HVR) of the HLA–DRB1 gene. The HLA–DRB1 association of PMR and GCA can be distinguished from that of RA, which is linked to a sequence motif in the third HVR of DRB1 alleles. The differential role of distinct domains on HLA‐DR molecules suggests that multiple biologic functions are regulated by these molecules and that they contribute differently to disease mechanisms. The similarities in the distribution of HLA–DRB1 alleles in PMR and GCA indicates that HLA–DRB1 alleles are not predictive for progression of PMR to the vasculitic lesions that are pathognomonic for GCA.
Intraarticular injections of hyaluronan in patients with cartilage abnormalities and knee pain
Authors: Dahlberg Leif , Lohmander L. Stefan , Ryd Leif 
Published: February 2007

AbstractObjective. To compare the effect of intraarticular injections of hyaluronan and placebo (vehicle, saline) in patients with knee pain on exertion and with joint cartilage abnormalities.Methods. Fifty‐two patients with arthroscopically verified deep cartilage fissures and villus‐like flakes in the symptomatic knee were randomly assigned to receive intraarticular injections of 2.5 ml of either hyaluronan or vehicle, weekly for 5 weeks. The effect was evaluated by both primary and secondary parameters of efficacy at 2, 4, 13, 26, and 52 weeks.Results. At the followup visits, both groups had improvement from baseline; however, there was no difference between the groups in any of the relevant variables at any time point.Conclusion. The effects of intraarticular hyaluronan do not differ significantly from those of placebo in patients with knee pain and cartilage disease.
Integrin expression by human articular chondrocytes
Authors: Woods Virgil L. , Schreck Paul J. , Gesink Dirk S. , Pacheco Hector O. , Amiel David , Akeson Wayne H. , Lotz Martin 
Published: February 2007

AbstractObjective. To perform a comprehensive analysis of the integrin forms expressed by normal human articular chondrocytes.Methods. Cartilage sections and collagenase‐released chondrocytes were probed with a comprehensive panel of integrin isoform–specific monoclonal antibodies (MAb), using in situ immunohistochemistry techniques, indirect immunofluorescence and flow cytometry, and immunoprecipitation/sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS‐PAGE).Results. Chondrocytes in cartilage sections reacted with MAb specific for the α5, αv, and β1 integrin subunits and the αvβ3 and αvβ5 heterodimers. They also reacted with a polyclonal antibody specific for the intracytoplasmic portion of the α1 subunit. MAb specific for the αv subunit reacted more strongly with chondrocytes near the articular surface than with those in deeper layers of cartilage, and the αvβ3‐specific MAb reacted exclusively with chondrocytes within the most superficial 30 μm of cartilage. Flow cytometric analysis and SDS‐PAGE analysis of immunoprecipitates prepared from extracts of cell‐surface radioiodinated chondrocytes confirmed the above observations, and additionally revealed the presence of the α3β1 integrin.Conclusion. Normal human articular chondrocytes prominently display substantial quantities of the α1β1, α5β1, and αvβ5 integrin heterodimers, as well as lesser quantities of the α3β1 and αvβ3 heterodimers, The αv subunit–containing integrins are detected more readily on the more superficial chondrocytes than on chondrocytes deep within cartilage. These observations provide the basis for analysis of the role of chondrocyte integrins in cartilage homeostasis and in the pathogenesis of joint diseases.
Effect of low‐dose cyclosporin a on systemic lupus erythematosus disease activity
Authors: Tokuda Michiaki , Kurata Noriyuki , Mizoguchi Akihito , Inoh Masayuki , Seto Kunio , Kinashi Makoto , Takahara Jiro 
Published: February 2007

AbstractObjective. To determine the effect of low‐dose cyclosporin A (CSA) treatment on disease activity in systemic lupus erythematosus (SLE).Methods. All patients in the study had active disease as defined by at least the presence of a low CH50 level. Patients were initially given 3 mg/kg/day of CSA. Dosages were adjusted individually at every visit, according to both clinical and laboratory data.Results. Eleven women with SLE were enrolled in the study; 10 were evaluable. After 20 weeks of CSA treatment, the mean score for disease activity on the SLE Disease Activity Index decreased significantly, from 10.6 to 3.8 (P = 0.02). The titer of antinuclear antibodies decreased in 8 patients and the level of anti‐DNA antibodies decreased in 5. Side effects included hypertension (40%), hypertrichosis (30%), gingival hypertrophy (10%), and a rise in the blood urea nitrogen level. Serum creatinine levels remained unchanged.Conclusion. The favorable responses observed in our patients strongly suggest that low‐dose CSA can reduce the disease activity of SLE.
Kidney biopsy in systemic lupus erythematosus
Authors: Mclaughlin John R. , Bombardier Claire , Farewell Vernon T. , Gladman Dafna D. , Urowitz Murray B. 
Published: February 2007

AbstractObjective. To examine the importance of renal biopsy as a predictor of death due to any cause in patients with systemic lupus erythematosus (SLE).Methods. The study included 123 SLE patients who had a renal biopsy between 1970 and 1984 and were followed up as part of a prospective study. Data were initially analyzed to identify clinical and laboratory features that were significantly associated with the risk of dying. Renal biopsy variables were then examined to determine whether they contributed additional information about prognosis.Results. The clinical and laboratory factors most closely associated with the risk of dying in multivariate analyses were the serum creatinine level and the SLE Disease Activity Index score. The presence of chronic renal lesions on biopsy contributed significantly to the prognostic information offered by clinical and laboratory factors in the subset of patients who had normal serum creatinine levels—the majority (85%) of patients in this study.Conclusion. These results indicate that renal biopsy serves an important role in the assessment of prognosis in patients who do not have advanced renal disease.
Association between antiphospholipid antibodies and epilepsy in patients with systemic lupus erythematosus
Authors: Herranz M. Teresa , Rivier Gilles , Khamashta Munther A. , Blaser Klaus U. , Hughes Graham R. V. 
Published: February 2007

AbstractObjective. To determine whether the occurrence of seizures is correlated with the presence of serum antiphospholipid antibodies (aPL) in systemic lupus erythematosus (SLE) patients.Methods. The study included 221 unselected patients with SLE. Of these, 21 patients with epileptic seizures not attributed to any cause other than SLE were identified. Epilepsy was diagnosed by clinical history and electroencephalography. Blood samples were tested for the presence of antibodies to cardiolipin (aCL, IgG and IgM isotypes) and lupus anticoagulant (LAC).Results. LAC was detected in 43.8% of the patients with epilepsy and in 20.8% of controls (P = 0.057). A statistically significant association was found between moderate‐to‐high titers of IgG aCL and the presence of seizures (P = 0.02). Brain computed tomography and/or magnetic resonance imaging scanning was performed in 14 patients. All patients with abnormal features found on these tests had positive aPL (P = 0.03). Nine patients (42.9%) had at least 1 of the classic features associated with the aPL syndrome.Conclusion. We confirmed that epilepsy as a primary neuropsychiatric event is significantly associated with moderate‐to‐high titers of IgG aCL in SLE patients. Our results suggest that aPL could have a role in the etiopathogenesis of epilepsy in SLE.