bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemokine receptor expression and in vivo signaling pathways in the joints of rats with adjuvant‐induced arthritis
Authors: Shahrara Shiva , Amin Mohammad A. , Woods James M. , Haines G. Kenneth , Koch Alisa E. 
Published: December 2003

AbstractObjectiveThis study was undertaken to characterize the role of CC chemokines and their receptors in rat adjuvant‐induced arthritis (AIA), a model for rheumatoid arthritis (RA). Furthermore, we investigated the signaling pathways associated with CC receptors as well as the cell type distribution of the receptors.MethodsUsing TaqMan real‐time reverse transcription–polymerase chain reaction, Western blot analysis, and immunohistochemistry, we defined chemokine and chemokine receptor messenger RNA (mRNA) expression, CC chemokine receptor (CCR) protein activation during the disease course, CCR‐associated signaling pathways, and immunopositive CCR5, phosphorylated signal transducer and activator of transcription 1 (p‐STAT‐1), and p‐STAT‐3 cells in rat AIA versus control joints.ResultsWe showed significant up‐regulation of CCR1, CCR2, CCR5, and macrophage inflammatory protein 1β/CCL4 mRNA in AIA on post–adjuvant injection day 18, coincident with peak inflammation. Additionally, increases in tyrosine phosphorylation of CCR1 (days 14, 18, 21, and 24), CCR2 (days 14 and 18), and CCR5 (days 14, 18, and 21) were detected in AIA rats compared with control (nonarthritic) rats. JAK‐1, STAT‐1, and STAT‐3 were associated with CCR1 and were highly tyrosine phosphorylated on days 14 and 18. Moreover, CCR2 was associated with JAK‐2, STAT‐1, and STAT‐3 on day 18. The association of STAT‐1 and STAT‐3 with CCR5 on days 18 and 21 correlated with JAK‐1 phosphorylation and binding on day 18. However, the activation of JNK was not associated with CCR5 activation in rat AIA. Immunohistochemical analysis demonstrated that the expression of CCR5, p‐STAT‐1, and p‐STAT‐3 was detected on synovial lining cells, macrophages, and endothelial cells in arthritic rat ankles on post–adjuvant injection day 18. While the majority of the CCR5 and p‐STAT‐1 immunostaining was on synovial lining cells and macrophages, p‐STAT‐3 was predominantly expressed on endothelial cells.ConclusionCCR1, CCR2, and CCR5 mRNA expression and tyrosine phosphorylation increased with peak inflammation in the AIA model. CCR1, CCR2, and CCR5 tyrosine phosphorylation are associated with the JAK/STAT‐1/STAT‐3 pathway at different stages of rat AIA, as well as with macrophage and endothelial cell infiltration. However, their signaling activation overlaps with peak inflammation. Up‐regulation and activation of CCRs may play a role in macrophage and endothelial cell infiltration in rat AIA joints in addition to activating the associated signaling pathways. The downstream intermediate signaling proteins associated with CC receptors may be used as potential tools to control inflammation in RA.
N‐terminal pro–brain natriuretic peptide as a diagnostic marker of early pulmonary artery hypertension in patients with systemic sclerosis and effects of calcium‐channel blockers
Authors: Allanore Y. , Borderie D. , Meune C. , Cabanes L. , Weber S. , Ekindjian O. G. , Kahan A. 
Published: December 2003

AbstractObjectiveTo evaluate N‐terminal pro–brain natriuretic peptide (NT‐proBNP) as a marker of early pulmonary artery hypertension (PAH) and to study changes in the levels of this marker following treatment with dihydropyridine‐type calcium‐channel blocker (DTCCB) in patients with systemic sclerosis (SSc).MethodsWe evaluated 40 consecutive SSc patients who had been hospitalized for followup care (mean ± SD age 56 ± 11 years and mean ± SD duration of cutaneous disease 9 ± 9 years; 27 with limited cutaneous and 13 with diffuse cutaneous disease) but who had no clinical symptoms of heart failure and had a normal left ventricular ejection fraction. At baseline, 10 patients had PAH, defined as a systolic pulmonary artery pressure (sPAP) >40 mm Hg, as measured by echocardiography. Levels of NT‐proBNP were determined at baseline (after discontinuation of DTCCB treatment for 72 hours), after taking 3 doses of DTCCB following treatment reinitiation (assessment 1), and after 6–9 months of continuous DTCCB treatment (assessment 2) in the 20 patients who attended regular appointments (including the 10 patients with PAH at baseline).ResultsAt baseline, 13 patients had high NT‐proBNP values for their ages. High NT‐proBNP levels identified patients with PAH with a sensitivity of 90%, a specificity of 90.3%, a positive predictive value of 69.2%, and a negative predictive value of 96%. The NT‐proBNP level correlated with the sPAP (r = 0.44; P = 0.006). By assessment 1, the number of patients with PAH and high levels of NT‐proBNP had decreased from 9 of 10 to 2 of 10 (P = 0.02). This decrease was partially sustained at assessment 2 (4 of 10 patients; P = 0.06).ConclusionNT‐proBNP is a useful biologic marker that can be used to diagnose early PAH in SSc patients without clinical heart failure. Measurement of NT‐proBNP may be valuable for the evaluation of treatment with DTCCB and vasodilators in patients with PAH.
Intravenous immunoglobulin abrogates dendritic cell differentiation induced by interferon‐α present in serum from patients with systemic lupus erythematosus
Authors: Bayry Jagadeesh , Lacroix‐Desmazes Sébastien , Delignat Sandrine , Mouthon Luc , Weill Bernard , Kazatchkine Michel D. , Kaveri Srini V. 
Published: December 2003

AbstractObjectiveAlterations in the function of dendritic cells (DCs) may explain the systemic autoimmune responses that characterize systemic lupus erythematosus (SLE). Even though several reports have documented the beneficial effect of intravenous immunoglobulin (IVIG) in SLE, the underlying mechanisms of action remain poorly understood. Considering the effect of serum factors, including interferon‐α (IFNα), on the activity of DCs, we investigated the effects of IVIG on the differentiation of DCs mediated by serum from SLE patients.MethodsDCs were differentiated from peripheral blood monocytes obtained from SLE patients and from healthy blood donors, in the presence of SLE serum. IVIG was used at a concentration of 0.15 mM. A functional assay was performed to assess the inhibitory effect of IVIG on the uptake of nucleosomes by DCs.ResultsIVIG interfered with the differentiation of DCs from SLE patients and healthy donors cultured in the presence of SLE serum. Treatment of DCs with IVIG inhibited the ingestion of nucleosomes by immature DCs, by up to 36%.ConclusionThe present findings indicate that IVIG, by down‐regulating the IFNα‐mediated differentiation of DCs and by inhibiting uptake of nucleosomes, may exert an essential immunoregulatory effect in SLE patients at the onset of the immune response, at the DC level. Given the critical role of HLA molecules and the costimulatory signals delivered by CD80 and CD86 in optimal antigen presentation and T cell activation, inhibition of expression of HLA and CD80/CD86 on DCs by IVIG offers a plausible explanation for the efficacy of IVIG in SLE and other immune‐mediated inflammatory conditions.
Indentation testing of human cartilage: Sensitivity to articular surface degeneration
Authors: Bae Won C. , Temple Michele M. , Amiel David , Coutts Richard D. , Niederauer Gabriele G. , Sah Robert L. 
Published: December 2003

AbstractObjectiveTo determine, for clinical indentation testing of human articular cartilage, the effects of aging and degeneration on indentation stiffness and traditional indices of cartilage degeneration; the relationship between indentation stiffness and indices of degeneration; and the sensitivity and specificity of indentation stiffness to cartilage degeneration.MethodsOsteochondral cores from femoral condyles of cadaveric human donors were harvested. Samples were distributed into experimental groups based on donor age (young [20–39 years], middle [40–59 years], and old [≥60 years]), and a macroscopic articular surface appearance that was either normal or mildly degenerate, without deep erosion. Samples were analyzed for indentation stiffness, cartilage thickness, India ink staining (quantitated as the reflected light score), and Mankin‐Shapiro histopathology score.ResultsIndentation stiffness, India ink staining, and the histopathology score each varied markedly between normal‐sample and degenerate‐sample groups but varied relatively little between normal samples obtained from different age groups. A decrease in indentation stiffness (softening) correlated with a decrease in the reflectance score and an increase in the overall histopathology score, especially the surface irregularity component of the histopathology score. Receiver operating characteristic analysis suggested that the indentation testing could accurately detect cartilage degeneration as indicated by macroscopic appearance, India ink staining, and histopathology score.ConclusionThe indentation stiffness of the normal to mildly degenerate samples tested in this study was sensitive to mild degeneration at the articular surface and was insensitive to changes associated with normal aging or to slight variations in cartilage thickness. This suggests that indentation testing may be a useful clinical tool for the evaluation of early‐stage degenerative changes in articular cartilage.
Rheumatoid arthritis of the shoulder joint: Comparison of conventional radiography, ultrasound, and dynamic contrast‐enhanced magnetic resonance imaging
Authors: Hermann Kay‐Geert A. , Backhaus Marina , Schneider Udo , Labs Karsten , Loreck Dieter , Zühlsdorf Svenda , Schink Tania , Fischer Thomas , Hamm Bernd , Bollow Matthias 
Published: December 2003

AbstractObjectiveTo determine the role of ultrasound and magnetic resonance imaging (MRI) compared with conventional radiography in the detection of chronic and acute inflammatory manifestations of rheumatoid arthritis (RA) of the shoulder joint.MethodsForty‐three consecutive patients with known RA prospectively underwent clinical examination, radiography, ultrasound, and MRI of the shoulder joints. Each patient was assigned a clinical/laboratory score consisting of 7 parameters, including measurements of shoulder mobility, the erythrocyte sedimentation rate, and C‐reactive protein level. Conventional radiography was standardized and performed in 2 planes. Ultrasound was performed in 10 predefined planes using a 7.5‐MHz linear transducer. MRI at 1.5T comprised transverse and oblique coronal T1‐ and T2*‐weighted fast spin‐echo, gradient‐echo (GRE), and inversion‐recovery sequences with a matrix size of up to 512 pixels. A dynamic T1‐weighted GRE sequence was acquired with intravenous administration of contrast medium. Erosions were assessed using all 3 imaging techniques on a 4‐point scale. Soft‐tissue involvement was evaluated according to the presence of synovitis, tenosynovitis, and bursitis on ultrasound and MRI. The results in the study group were compared with those obtained in a control group of 10 patients with shoulder pain.ResultsIn the study group, erosions of the humeroscapular joint were detected by conventional radiography in 26 patients, by ultrasound in 30 patients, and by MRI in 39 patients; the differences were statistically significant for the comparisons of conventional radiography with MRI and for ultrasound versus MRI (P < 0.0001). Conventional radiography detected 12 erosions of the scapula and MRI detected 15. Synovitis was demonstrated in 12 patients by ultrasound and in 27 patients by MRI (P = 0.0003). Tenosynovitis was observed in 15 patients by ultrasound and in 28 patients by MRI (P = 0.0064). Bursitis was detected in 13 patients by ultrasound and in 18 patients by MRI. The findings on dynamic contrast‐enhanced MRI correlated significantly with the detection of synovitis by ultrasound and erosions by static MRI (P < 0.05).ConclusionUltrasound and MRI supplement conventional radiography in assessing the shoulder joint. Although conventional radiography can be used as the sole method of following up known joint destruction in RA, ultrasound and, preferably, MRI are recommended as additional techniques in the initial diagnostic evaluation when radiography yields negative results.
Incidence and predictors of large‐artery complication (aortic aneurysm, aortic dissection, and/or large‐artery stenosis) in patients with giant cell arteritis: A population‐based study over 50 years
Authors: Nuenninghoff Dirk M. , Hunder Gene G. , Christianson Teresa J. H. , McClelland Robyn L. , Matteson Eric L. 
Published: December 2003

AbstractObjectiveTo determine the incidence and predictors of large‐artery complication (aortic aneurysm, aortic dissection, and/or large‐artery stenosis) in patients with giant cell arteritis (GCA).MethodsThe cohort of all residents of Olmsted County, Minnesota, in whom GCA was diagnosed between January 1, 1950, and December 31, 1999, was followed up. The incidence of aortic aneurysm, aortic dissection, and large‐artery stenosis was determined. Possible predictors and correlates of large‐artery complication were assessed.ResultsForty‐six incident cases of large‐artery complication (representing 27% of the 168 patients in the cohort) were identified. These included 30 incident cases (18%) of aortic aneurysm and/or aortic dissection. Of these cases, 18 (11%) involved the thoracic aorta, with aortic dissection developing in 9 (5%). There were 21 incident cases (13%) of large‐artery stenosis. Fifteen patients (9%) had incident cervical artery stenosis, and 6 (4%) had incident subclavian/axillary/brachial artery stenosis. One patient (0.6%) had incident iliac/femoral artery stenosis attributable to GCA. Hyperlipidemia and coronary artery disease were associated with aortic aneurysm and/or dissection (P< 0.05 for both). Cranial symptoms (headache, scalp tenderness, abnormal temporal arteries) were negatively associated with large‐artery stenosis (hazard ratio [HR] 0.10 [95% confidence interval (95% CI) 0.03–0.35,P< 0.0005]), as was a higher erythrocyte sedimentation rate (HR 0.80 [95% CI 0.67–0.95,P< 0.05] per 10 mm/hour).ConclusionLarge‐artery complication is common in GCA. Increased awareness of large‐artery complication in GCA, particularly early‐occurring aortic dissection, may decrease associated mortality.
B lymphocyte stimulator overexpression in patients with systemic lupus erythematosus: Longitudinal observations
Authors: Stohl William , Metyas Samy , Tan Soon‐Min , Cheema Gurtej S. , Oamar Bonifacia , Xu Dong , Roschke Viktor , Wu Youmei , Baker Kevin P. , Hilbert David M. 
Published: December 2003

AbstractObjectiveTo assess the overexpression of B lymphocyte stimulator (BLyS) over time in patients with systemic lupus erythematosus (SLE).MethodsSixty‐eight SLE patients were followed up longitudinally for a median 369 days. At each physician encounter, disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index, and blood was collected for determination of the serum BLyS level, blood BLyS messenger RNA (mRNA) level, and cell surface BLyS expression. Twenty normal control subjects underwent similar laboratory evaluations.ResultsIn contrast to the uniformly normal serum BLyS and blood BLyS mRNA phenotypes in control subjects, SLE patients displayed marked heterogeneity, with 50% and 61% of patients manifesting persistently or intermittently elevated serum BLyS and blood BLyS mRNA phenotypes, respectively. Surface BLyS expression by SLE peripheral blood mononuclear cells was also often increased. Treatment of patients who had elevated serum BLyS levels with intensive courses of high‐dose corticosteroids resulted in marked reductions in serum BLyS levels, and tapering of the corticosteroid dosage often resulted in increases in serum BLyS levels. Serum BLyS levels generally correlated with anti–double‐stranded DNA (anti‐dsDNA) titers (in those with detectable anti‐dsDNA titers), but changes in serum BLyS levels did not correlate with changes in disease activity in individual patients. Serum BLyS phenotype did not associate with specific organ system involvement.ConclusionDysregulation of BLyS over extended periods of time is common in patients with SLE. Neutralization of BLyS activity with an appropriate BLyS antagonist may be therapeutically beneficial.
Gene deletion of either interleukin‐1β, interleukin‐1β–converting enzyme, inducible nitric oxide synthase, or stromelysin 1 accelerates the development of knee osteoarthritis in mice after surgical transection of the medial collateral ligament and partial medial meniscectomy
Authors: Clements Kristen M. , Price Joanne S. , Chambers Mark G. , Visco Denise M. , Poole A. Robin , Mason Roger M. 
Published: December 2003

AbstractObjectiveTo investigate the development of osteoarthritis (OA) after transection of the medial collateral ligament and partial medial meniscectomy in mice in which genes encoding either interleukin‐1β (IL‐1β), IL‐1β–converting enzyme (ICE), stromelysin 1, or inducible nitric oxide synthase (iNOS) were deleted.MethodsSectioning of the medial collateral ligament and partial medial meniscectomy were performed on right knee joints of wild‐type and knockout mice. Left joints served as unoperated controls. Serial histologic sections were obtained from throughout the whole joint of both knees 4 days or 1, 2, 3, or 4 weeks after surgery. Sections were graded for OA lesions on a scale of 0–6 and were assessed for breakdown of tibial cartilage matrix proteoglycan (aggrecan) and type II collagen by matrix metalloproteinases (MMPs) and aggrecanases with immunohistochemistry studies using anti‐VDIPEN, anti‐NITEGE, and Col2‐3/4Cshort neoepitope antibodies. Proteoglycan depletion was assessed by Alcian blue staining and chondrocyte cell death, with the TUNEL technique.ResultsAll knockout mice showed accelerated development of OA lesions in the medial tibial cartilage after surgery, compared with wild‐type mice. ICE‐, iNOS‐, and particularly IL‐1β–knockout mice developed OA lesions in the lateral cartilage of unoperated limbs. Development of focal histopathologic lesions was accompanied by increased levels of MMP‐, aggrecanase‐, and collagenase‐generated cleavage neoepitopes in areas around lesions, while nonlesional areas showed no change in immunostaining. Extensive cell death was also detected by TUNEL staining in focal areas around lesions.ConclusionWe postulate that deletion of each of these genes, which encode molecules capable of producing degenerative changes in cartilage, leads to changes in the homeostatic controls regulating the balance between anabolism and catabolism, favoring accelerated cartilage degeneration. These observations suggest that these genes may play important regulatory roles in maintaining normal homeostasis in articular cartilage matrix turnover.
Successful tumor necrosis factor α blockade treatment in therapy‐resistant sarcoidosis
Authors: Ulbricht Kai U. , Stoll Matthias , Bierwirth Janine , Witte Torsten , Schmidt Reinhold E. 
Published: December 2003

AbstractSarcoidosis is a multisystemic disorder histologically characterized by a noncaseating granulomatous inflammatory process. The etiology remains unclear, but tumor necrosis factor α seems to play a crucial role. Herein we describe a patient with severe sarcoidosis involving the lung and liver. Various treatment regimens with azathioprine, methotrexate, cyclophosphamide, and pentoxifylline failed to control the disease. Therefore, salvage therapy with infliximab was commenced. Arthritis and pulmonary and liver involvement improved. We were then able to taper the corticosteroid treatment to a lower‐dose regimen with no need for additional immunosuppressive treatment. To our knowledge, this is the first reported case of successful treatment of multiorgan sarcoidosis that was previously resistant to conventional therapy.
Successful treatment of multicentric reticulohistiocytosis with alendronate: Evidence for a direct effect of bisphosphonate on histiocytes
Authors: Goto Hitoshi , Inaba Masaaki , Kobayashi Keisuke , Imanishi Yasuo , Kumeda Yasuro , Inui Kentaro , Okada Fumihiko , Nishizawa Yoshiki 
Published: December 2003

AbstractWe describe the case of a 44‐year‐old Japanese woman with severe nodular erythematous skin lesions and arthritis mutilans who was admitted for further treatment of multicentric reticulohistiocytosis. Skin and synovial biopsies showed heavy infiltration with tartrate‐resistant acid phosphatase–positive histiocytes and multinucleated giant cells. Immunohistochemical analysis showed that some of the mononuclear cells in the skin were positive for RANKL. After 1 month of Alendronate, an aminobisphosphonate, given at a dosage of 10 mg once a week intravenously for the first 6 weeks and then once a month thereafter, the arthritis and skin nodules improved, and the remission has continued for more than 2 years. The findings in this patient suggest that osteoclast‐like multinucleated giant cells differentiate locally in the skin from infiltrating histiocytes with the help of RANKL‐positive stromal cells and that alendronate acts directly on cells of monocyte/macrophage lineage in humans. Thus, alendronate should be added to the list of drugs for the treatment of multicentric reticulohistiocytosis.
Efficacy and safety of tacrolimus in patients with rheumatoid arthritis: A double‐blind trial
Authors: Yocum David E. , Furst Daniel E. , Kaine Jeffrey L. , Baldassare Andrew R. , Stevenson Jon T. , Borton Mary Ann , Mengle‐Gaw Laurel J. , Schwartz Benjamin D. , Wisemandle Wayne , Mekki Qais A. 
Published: December 2003

AbstractObjectiveTo evaluate the efficacy and safety of tacrolimus as monotherapy in controlling the signs and symptoms of patients with rheumatoid arthritis (RA).MethodsThis was a 6‐month, phase III, double‐blind, multicenter study. Patients with active RA who had discontinued all disease‐modifying antirheumatic drugs (DMARDs) for an appropriate washout period (at least 1 month) and who, after the washout period, had a stable joint count (at least 10 tender/painful joints and 7 swollen joints) were stratified according to DMARD intolerance or DMARD resistance, and randomized to receive a single daily oral dose of placebo, tacrolimus 2 mg, or tacrolimus 3 mg.ResultsA total of 464 patients received at least 1 dose of study drug. Baseline characteristics were similar among the 3 treatment groups. American College of Rheumatology 20% improvement (ACR20) success (defined as completion of 6 months of treatment and an ACR20 response at the month 6 visit) for the placebo, tacrolimus 2 mg, and tacrolimus 3 mg groups was 10.2%, 18.8% (P < 0.05 versus placebo), and 26.8% (P < 0.0005 versus placebo), respectively. At the end of treatment, the ACR20 and ACR50 response rates in the 3‐mg group were 32.0% (P < 0.005 versus placebo) and 11.8% (P < 0.05 versus placebo), respectively. DMARD‐intolerant patients had better ACR response rates than did DMARD‐resistant patients. Although serum creatinine levels increased by ≥40% from baseline at some time during the trial in 20% and 29% of patients receiving tacrolimus 2 mg/day and 3 mg/day, respectively, the serum creatinine level remained within the normal range throughout the trial in ∼90% of patients.ConclusionTacrolimus, at dosages of both 2 mg/day and 3 mg/day, is efficacious and safe as monotherapy for patients with active RA, but treatment with the 3‐mg dose of tacrolimus resulted in generally better ACR response rates.