bluuebunny/crossref_metadata_2025_split huggingface dataset:
A molecular and serologic analysis of the major histocompatibility complex and complement component c4 in systemic sclerosis
Authors: Briggs David , Stephens Clare , Vaughan Robert , Welsh Ken , Black Carol 
Published: February 2007

AbstractObjective. To investigate the contributions of the major histocompatibility complex (MHC) and C4 alleles to systemic sclerosis (SSc), and to pulmonary fibrosis and autoantibody expression in SSc, by analysis at the DNA level.Methods. One hundred fifteen patients with SSc were tested serologically for alleles of the class I MHC loci, and were tested for class II alleles (DRB, DQA, and DPB) by a combination of restriction fragment length polymorphism (RFLP) analysis and oligonucleotide probes with polymerase chain reaction amplification. C4 was studied by protein phenotyping and RFLP analysis in 80 patients. Correlations were made between disease status, pulmonary fibrosis, and expression of anticentromere antibodies (ACA) and anti–Scl‐70.Results. The C4A‐null phenotype was found to provide the strongest disease association factor of the MHC region (P = 0.000064, relative risk [RR] = 2.8, etiologic fraction [EF] = 32.1). The primary MHC susceptibility allele was found to be DQA2 (Pcorrr = 0.0009, RR = 2.5, EF = 35.6), which is in linkage disequilibrium with both DR3 and DR11. DR2 was protective, but only for female patients (P = 0.0021, RR = 0.42, protective fraction = 19.4). DR52a was the primary MHC allele associated with pulmonary fibrosis in SSc patients. Expression of ACA was associated with the presence of either DR1 or DR4 (P = 0.0015, RR = 6.7, EF = 78.0). Anti–Scl‐70 expression correlated with an acidic residue of DPβ (DPB1:69:E) (P = 0.0063, RR = 4.6, EF = 53.1).Conclusion. Of all the potential markers of disease susceptibility analyzed, the C4A locus was the strongest. C4AQ0 and DQA2 are independent susceptibility factors for SSc. The development of pulmonary fibrosis in SSc patients can be predicted using combined MHC and autoantibody analysis. The MHC alleles associated with the expression of disease‐specific autoantibodies are not markers for disease susceptibility.
Fcγ receptor activation of neutrophils in cryoglobulin‐induced leukocytoclastic vasculitis
Authors: Hundt Matthias , Zielinska‐Skowronek Margot , Schmidt Reinhold E. 
Published: February 2007

AbstractObjective. The role of Fcγ receptors (FcγR) in type I cryoglobulinemia was investigated to characterize novel mechanisms of neutrophil activation in the pathogenesis of leukocytoclastic vasculitis.Methods. Neutrophils from healthy donors were incubated with purified monoclonal IgG1k cryoglobulin complexes in vitro. Changes in surface antigen expression and mechanisms of intracellular hydrogen peroxide production and calcium release were measured by flow cytometry.Results. After incubation for 2 hours, surface expression of FcγRI (CD64), CD66, and CD67 was up‐regulated; FcγRII (CDw32), FcγRIII (CD16), and LAM‐1 were down‐regulated. Using solubilized and complexed cryoglobulins, it was demonstrated that complex formation is necessary to induce intracellular H2O2 production and calcium release from intracellular stores. Both H2O2 generation and calcium mobilization could be inhibited by pretreatment with F(ab')2 fragments of monoclonal antibodies (MAb) against FcγRIII. In contrast, Fab fragments of anti‐FcγRII MAb failed to block these activations. Neither the cryoglobulin complex–induced production of H2O2 nor the increase in cytoplasmic calcium was affected by treatment with pertussis toxin, which suggests that pertussis toxin–sensitive G proteins are not involved in signal transduction.Conclusion. These results indicate that FcγRIII plays a major role in the pathogenesis of leukocytoclastic vasculitis.
Triggering and exacerbation of autoimmune arthritis by the mycoplasma arthritidis superantigen mam
Authors: Cole Barry C. , Griffiths Marie M. 
Published: February 2007

AbstractObjective. It has been postulated that superantigens might play a role in the human rheumatic diseases, by activation of self‐reactive T cells or by induction of autoantibodies. The Mycoplasma arthritidis superantigen MAM, which is derived from a naturally occurring murine arthitogenic mycoplasma, uses certain Vβ chains of the murine T cell receptor (TCR) that have been proposed to be involved in murine collagen‐induced arthritis (CIA). The present study was designed to determine whether MAM influences the course of arthritis mediated by immunization with porcine type II collagen (PII).Methods. MAM or phosphate buffered saline (PBS) was injected locally or systemically into mice convalescing from CIA or mice suboptimally immunized with collagen.Results. In contrast to PBS, MAM caused an exacerbation of arthritis in mice that were recovering from CIA. MAM also triggered arthritis onset in mice that had been suboptimally immunized with PII up to 160 days previously. Injection of MAM during the onset phase of CIA also triggered and enhanced the severity of arthritis in mice given low doses of PII.Conclusion. MAM can both trigger and exacerbate murine autoimmune arthritis induced by immunization with type II collagen. Since T cells bearing the same Vβ TCRs as are used by MAM have been found to comprise a major portion of the activated cells in the synovial tissue of patients with rheumatoid arthritis, it is possible that superantigens similar to MAM may play a role in this human disease.
The repertoire of rheumatoid factor–producing b cells in normal subjects and patients with rheumatoid arthritis
Authors: He Xiaowen , Goronzy Jörg J. , Weyand Cornelia M. 
Published: February 2007

AbstractObjective. To compare the B cell repertoire of normal individuals and patients with rheumatoid arthritis (RA) and, specifically, to identify precursor B cells with the potential to secrete rheumatoid factor (RF) and to understand the T helper cell requirements for the production of this autoantibody.Methods. Frequencies of precursors of IgM, IgG, and RF‐producing B cells were measured in a limiting‐dilution system. Two distinct sources of T cell help were compared. T cell help was provided by anti‐CD3–activated CD4+ human T cell clones, or T cell–B cell interaction was facilitated by the bacterial superantigen staphylococcal enterotoxin D (SED).Results. A subset of 2–14% of peripheral blood B cells secreted IgM and IgG in SED‐driven cultures. The SED‐responsive B cell subpopulation was present at 10 times higher frequency in normal donors compared with RA patients. However, the repertoires were very similar, particularly for RF+ precursors, which represented approximately one‐third of all SED‐responsive B cells. In normal individuals, most of these RF+ precursor B cells did not respond to anti‐CD3–activated T helper cells, with only a very small fraction of B cells activated by anti‐CD3–driven helper cells maturing into RF‐secreting B cells (from 1 of 182 to 1 of 889 IgM‐producing B cells). This subset was expanded approximately 50‐fold in RA patients.Conclusion. Normal subjects and RA patients share a pool of B cells which secrete RF when activated in the presence of SED and T helper cells. These B cells are frequent and obviously anergic in normal individuals. The B cell subset with the potential to produce RF when help is provided in noncognate T–B interaction (anti‐CD3–driven T cells) is considerably expanded in RA patients, probably reflecting an increased responsiveness of such B cells to helper signals.
Connective tissue activation. xxxvi. the origin, variety, distribution, and biologic fate of connective tissue activating peptide–iii isoforms: characteristics in patients with rheumatic, renal, and arterial disease
Authors: Castor C. W. , Andrews P. C. , Swartz R. D. , Ellis S. G. , Hossler P. A. , Clark M. R. , Matteson E. L. , Sachter E. F. 
Published: February 2007

AbstractObjective. To determine the origin, distribution, and biologic fate of platelet‐derived connective tissue activating peptide–III (CTAP‐III), to define the relative amounts of the antigen forms (CTAP‐III, betathromboglobulin [β‐TG], neutrophil activating peptide–2 [NAP‐2]) in plasma of normal persons and those with rheumatic or end‐stage renal disease, and to define the isoforms of CTAP‐III in platelets, plasma, transudates, and tissue deposits.Methods. CTAP‐III in plasma was measured by enzyme‐linked immunosorbent assay, and growth promoting activity of CTAP‐III isoforms was tested in synovial and peritoneal cell cultures by measuring increased synthesis of 14C‐glycosaminoglycan (14C‐GAG) and 3H‐DNA. Isolated CTAP‐III was characterized by Western blotting, microsequencing, and mass spectrometry.Results. CTAP‐III was the primary isoform of this antigen family in normal platelets and platelet‐rich plasma; β‐TG and NAP‐2 accounted for <1% of CTAP‐III isoforms. Previously undescribed isoforms, i.e., CTAP‐III des 1, des 1–2, des 1–3, and a phosphate adduct of CTAP‐III, were observed in varying amounts. Elevated plasma levels of CTAP‐III antigen were found in a substantial fraction of rheumatic disease patients: 24% of those with rheumatoid arthritis, 36% of those with systemic sclerosis, and 15% of those with systemic lupus erythematosus. All 10 patients with end‐stage kidney disease had marked elevations of plasma CTAP‐III levels, which stimulated DNA and GAG synthesis by peritoneal cells in culture. Only large isoforms (such as CTAP‐III) were detected in venous plasma of normal subjects, rheumatic disease patients, and patients receiving long‐term dialysis. Normal human spleen and kidney contained substantial (μ/gm) amounts of CTAP‐III and traces of an isoform with the electrophoretic mobility of CTAP‐III des 1–15/NAP‐2. Liver, lung, and urine contained lesser (ng/gm) amounts of CTAP‐III.Conclusion. These data show that, among the 10 known isoforms, intact CTAP‐III itself was the major circulating isoform (>90%), and β‐TG was the most rare (0–1%). Deposition of CTAP‐III in tissues, such as synovium, spleen, and kidney, is associated with partial processing to NAP‐2–like isoforms and the potential to induce neutrophil and fibroblast activation in patients with rheumatic or end‐stage renal disease.
Sensory nerves only temporarily protect the unstable canine knee joint from osteoarthritis. evidence that sensory nerves reprogram the central nervous system after cruciate ligament transection
Authors: O'connor B. L. , Visco D. M. , Brandt K. D. , Albrecht M. , O'connor A. B. 
Published: February 2007

AbstractObjective. The slow rate at which articular cartilage degrades in dogs after transection of the anterior cruciate ligament (ACLT) has been attributed to capsular thickening and buttressing by osteophytes. We investigated the roles of the peripheral and central nervous systems in protecting knee joints with chronic ACL deficiency from breakdown.Methods. Five groups of dogs were studied; all were killed 72 weeks after left knee surgery. Group A had ACLT, group B had ACLT followed 52 weeks later by ipsilateral L4–S1 dorsal root ganglionectomy (DRG), group C had DRG followed 2 weeks later by ACLT, group D had sham DRG followed 2 weeks later by ACLT, and group E had DRG followed 2 weeks later by sham ACLT.Results. Group E dogs did not develop knee pathology. All cruciate‐deficient knees were lax at the end of the study. The osteoarthritis (OA) that developed in groups A, B, and D was comparable (P > 0.05), and was significantly greater than that in group E (P < 0.05). Group C developed much more severe OA than any of the other groups (P < 0.05).Conclusion. Ipsilateral sensory input is temporarily important in protecting the unstable joint from rapid breakdown. Over time, the central nervous system apparently acquires the ability to protect the unstable joint without continued ipsilateral sensory input.
Takayasu arteritis with acute interstitial pneumonia and coronary vasculitis: expanding the spectrum. report of a case
Authors: Kreidstein Sharon H. , Lytwyn Alice , Keystone Edward C. 
Published: February 2007

AbstractWe describe the first reported case of Takayasu arteritis presenting as idiopathic adult respiratory distress syndrome, with a pathologic diagnosis of acute interstitial pneumonia. In the same patient, rarely occurring, diffuse coronary vasculitis developed. This case vividly illustrates the extensive, clinically significant vascular involvement that can occur in Takayasu arteritis, as well as the potential extravascular, multisystemic nature of the disease.
Effect of piroxicam on gait in patients with osteoarthritis of the knee
Authors: Schnitzer Thomas J. , Popovich Jovan M. , Andersson Gunnar B. J. , Andriacchi Thomas P. 
Published: February 2007

AbstractObjective. To determine whether the use of a nonsteroidal antiinflammatory drug (NSAID) in patients with painful osteoarthritis (OA) of the knee would result in alterations in specific biomechanical parameters of gait.Methods. Eighteen patients with symptomatic knee OA and varus knee deformity underwent initial clinical evaluation for pain and activities of daily living, and assessment of parameters of gait utilizing a well‐described computerized system. All patients were then treated with piroxicam at 20 mg once daily, and clinical and gait analyses were repeated after 4 weeks.Results. Fifteen of the 18 patients studied had a significant increase in the knee adduction moment after treatment. In the group as a whole there was a significant increase in knee adduction moment (mean percent body weight times height [%BWTH] 4.11 pretreatment versus 4.57 after 4 weeks of treatment; P < 0.01) and maximum quadriceps moment (mean %BWTH 2.13 pretreatment, 2.62 posttreatment; P < 0.01), as well as changes in other gait parameters that might be expected to be altered as a result of relief of pain. Sixteen of 18 patients experienced symptomatic relief, with a significant reduction in pain in the group as a whole after 4 weeks (P < 0.001).Conclusion. NSAID treatment in patients with knee OA results in a reduction in symptomatic pain and an increase in loading of the knee. Whether the increased loading is due to the analgesic effects of the treatment is unknown, but if so, the development of agents capable of relieving pain while reducing loads at the knee may be desirable.
DAB486IL‐2 fusion toxin in refractory rheumatoid arthritis
Authors: Sewell Kathryn Lea , Parker Karen C. , Woodworth Thasia G. , Reuben James , Swartz William , Trentham David E. 
Published: February 2007

AbstractObjective. To evaluate the safety and antiarthritic effects of DAB486IL‐2. This agent is a fusion toxin and the product of a synthetic gene, engineered by replacing the codons for the receptor‐binding domain of diphtheria toxin (DT) with the codons for human interleukin‐2 (IL‐2). DAB486IL‐2 targets cells expressing the 2‐chain, high‐affinity form of the IL‐2 receptor (IL‐2R), and achieves selective diphtheria toxin–mediated cytotoxicity of activated T cells by inhibition of protein synthesis.Methods. Nineteen patients with rheumatoid arthritis (RA) that had been refractory to methotrexate participated in an open‐label, phase I/II trial evaluating 3 dose levels of intravenous DAB486IL‐2 given for 5 or 7 consecutive days. Thirteen patients received additional courses, at higher doses if the original response had been inadequate or at an equivalent dose if the original course produced a response, for a total of 38 courses. Arthritis response was assessed at 28 days, with biweekly followup of patients with substantial response (⩾50% improved) or meaningful response (⩾25% improved). Laboratory monitoring included measurement of CD4+ cells and circulating shed IL‐2R.Results. Nine of 19 patients treated with high‐ or medium‐dose DAB486IL‐2 had a substantial or meaningful response after 1 or 2 treatment courses. No significant responses occurred with the low‐dose regimen. Clinical benefit was rapid, with full effect noted by 14 days following completion of infusions. Antibodies to DT developed in all patients, or levels of preexisting antibodies were boosted. Adverse effects included transient elevation of transaminase levels (55% of the patients), fever (40%), nausea or anorexia (30%), hypersensitivity (6%), and thrombocytopenia (5%). Repeat courses were associated with less transaminase elevation and were clinically effective despite induction of anti‐DT antibodies.Conclusion. The results of this open trial provide preliminary evidence for a potential therapeutic effect of DAB486IL‐2 in RA, with an acceptable safety profile. Reversible transaminase elevations limit escalation of the dosage beyond 0.1 mg/kg/day. A controlled study of DAB486IL‐2 is required to determine the efficacy of this high‐affinity IL‐2R–targeted fusion toxin in the treatment of RA.
Single‐photon–emission computed tomography analysis of cerebral blood flow in the evaluation of central nervous system involvement in patients with systemic lupus erythematosus
Authors: Rubbert A. , Marienhagen J. , Pirner K. , Manger B. , Grebmeier J. , Engelhardt A. , Wolf F. , Kalden J. R. 
Published: February 2007

AbstractObjective. Single‐photon–emission computed tomography (SPECT) scanning was used to detect potential central nervous system (CNS) involvement in patients with systemic lupus erythematosus (SLE), by determining cerebral blood flow abnormalities.Methods. SPECT scans were performed on 35 SLE patients, grouped into 3 categories: those without neuropsychiatric symptoms (n = 10), those with definite neurologic or psychiatric disorders (n = 10), and those with mild symptoms such as headache or memory disturbances (n = 15). SPECT scan features were classified as normal or as focal or diffuse defects in uptake.Results. SPECT findings were normal in 9 of the 10 patients without CNS symptoms, and abnormal in 9 of the 10 patients with overt neuropsychiatric disease (with motor or sensory deficits). Interestingly, only 4 of the 15 patients (26.7%) with mild symptoms suggestive of CNS disease had normal SPECT findings; the 11 remaining patients showed focal (53.3%) or diffuse (20%) uptake defects. An association between SPECT findings and disease duration was also observed, but there was no correlation of SPECT results with overall disease activity, serologic findings, or medications used.Conclusion. Our data suggest that in a substantial proportion of patients, SPECT analysis may provide additional information on potential CNS involvement, and may therefore be useful in therapeutic decisionmaking and disease monitoring in order to prevent CNS damage.
Nucleotide sequence analysis of thel and vh domains of five human igm directed to lamin b. evidence for an antigen‐driven process in the generation of human autoantibodies to lamin b
Authors: Mariette Xavier , Brouet Jean‐Claude , Danon Françoise , Tsapis Andréas , Lassoued Kaïss 
Published: February 2007

AbstractObjective. To gain insight into the genetic origin of human antilamin autoantibodies, we determined the nucleotide sequence of the light and heavy chain variable region (VL and VH) domains of 5 IgM antibodies directed to lamin B. These antibodies represent a distinct subset of antinuclear antibodies, and their presence is associated with a particular lupus‐like syndrome.Methods. We derived and cloned lymphoblastoid cell lines from peripheral blood B cells of 3 patients, selected anti–lamin B–producing subclones, and sequenced the messenger RNA coding for Ig heavy and light chains.Results. We isolated 2 subclones (1 IgMκ, 1 IgMλ) from one patient (FUR) and 2 subclones (both IgMλ) from another (HER). In contrast, all 8 lines derived from B cells isolated from the third patient (BEN) synthesized identical anti–lamin B IgMκ antibodies: All VL and VH domains from these 5 IgM were encoded by different VL or VH genes. DH regions were all different, and there was no restriction in the use of JL or JH segments. Analysis of the nucleotide sequence of the VL domains allowed the identification of the putative germinal gene in 3 instances (VκIV, Humkv325, and VλIII.1); the overall ratios of replacement:silent mutations (R:S) were 6.5 and 1.2 in the complementarity‐determining regions (CDRs) and framework regions (FRs), respectively. The 2 other λ sequences belonged to the VλIII family. With regard to VH domains, 3 of 5 derived from previously identified germline genes (VHIV 4.19, VHIV 4.22, and VHIII 9.1); the overall R:S ratio for these genes was 8 and 1.5 in CDRs and FRs, respectively.Conclusion. Taken together, these data provide evidence that the repertoire of human antilamin autoantibodies is not restricted and that the antigen (or another kind of selective pressure) plays a role in the generation of autoantibodies to lamin B. This hypothesis is in accordance with the reactivity of these antibodies to discrete epitopes of lamin B.
Association between reactive arthritis and antecedent infection with shigella flexneri carrying a 2‐md plasmid and encoding an hla–b27 mimetic epitope
Authors: Stieglitz H. , Lipsky P. 
Published: February 2007

AbstractObjective. To determine whether Shigella flexneri strains that cause enteric infection and are associated with reactive arthritis (ReA) carry a 2‐Md plasmid, pHS‐2, which encodes an HLA–B27 mimetic epitope.Methods. Plasmid DNA from Shigella isolates was characterized by DNA–DNA hybridization, restriction endonuclease digestion, and sequencing.Results. S flexneri strains associated with ReA carried a 2‐Md plasmid homologous to pHS‐2.Conclusion. The finding of pHS‐2 in additional Shigella strains associated with ReA underscores its potential importance in the etiology of the disease.
A quantitative assessment of limited joint mobility in patients with diabetes
Authors: Schulte L. , Roberts M. S. , Zimmerman C. , Ketler J. , Simon L. S. 
Published: February 2007

AbstractObjective. The syndrome of limited joint mobility is a common but not widely recognized musculoskeletal complication of diabetes. The purpose of this study was to further characterize this syndrome using quantitative goniometric measures.Methods. Cross‐sectional analysis of a sample population was performed to establish the prevalence, location, and severity of limited joint mobility and to determine its relationship to extraarticular manifestations and complications of diabetes. Passive range of motion of both upper extremities was measured by goniometry in 70 adult patients with insulin‐dependent diabetes mellitus and 70 nondiabetic controls who were group‐matched for age, sex, and general activity level. Joint mobility was assessed by both individual joint motions and a composite scoring technique.Results. Analysis of individual joints and composite scores revealed significant differences between dominant and nondominant extremities in both the control and the diabetic groups. Diabetic patients were generally less flexible than nondiabetic subjects throughout the arm, especially in shoulder and finger joints. In the full study population, multivariate analysis revealed that advanced age, male sex, and the presence of diabetes were associated with decreased passive range of motion for a majority of joints (P < 0.05). In the diabetes group, passive range of motion was significantly correlated (P < 0.05) with age, sex, duration of diabetes, and to a variable extent, glucose control, but was not correlated with the presence of clinically significant neuropathy, retinopathy, nephropathy, or peripheral vascular disease, with activity level, or with hand dominance. Stepwise regression analysis failed to identify single key joint motion(s) to serve as possible screening tests in predicting generalized limited joint mobility of the upper extremity. Finally, the effect of limb usage on range of motion in flexion may differ in diabetic and nondiabetic subjects.Conclusion. Limited joint mobility is a generalized phenomenon occurring throughout the upper extremities of many diabetic patients. It is significantly related to age, sex, and to a variable extent duration of diabetes and glucose control. It is not related to the standard complications of diabetes as defined in this study.