bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blockade of lymphotoxin pathway exacerbates autoimmune arthritis by enhancing the Th1 response
Authors: Han Shuhua , Zhang Xuejun , Marinova Ekaterina , Ozen Zeynep , Bheekha‐Escura Roy , Guo Linjie , Wansley Daniel , Booth George , Fu Yang‐Xin , Zheng Biao 
Published: September 2005

AbstractObjectiveTo study the role of the lymphotoxin (LT) signaling pathway in the development and pathogenesis of collagen‐induced arthritis (CIA), and to understand the mechanisms by which blockade of the LT pathway influences the arthritogenic response to type II collagen (CII).MethodsLTα‐deficient and wild‐type C57BL/6 mice were immunized with CII. Male DBA/1 mice were immunized with CII and treated with LTβ receptor immunoglobulin fusion protein (LTβR‐Ig) or control Ig. Mice were monitored for the development and severity of arthritis. The effects of LT blockade on immune responses were evaluated by cytokine production and antigen‐specific proliferation in vitro, the delayed‐type hypersensitivity (DTH) response, and serum levels of CII‐specific antibodies.ResultsCIA that developed in LTα‐deficient mice was more severe and prolonged than that which developed in wild‐type mice. Blocking LT signaling with LTβR‐Ig significantly exacerbated the disease. Exacerbation of CIA was associated with an enhanced Th1‐type response, including increased type 1 cytokine production, an enhanced DTH response, and elevated production of CII‐specific IgG2a antibodies.ConclusionBlockade of the LT signaling pathway exacerbates the development and progression of CIA, probably by skewing the Th1/Th2 balance that determines the outcome of autoimmune responses.
Interleukin‐17 receptor deficiency results in impaired synovial expression of interleukin‐1 and matrix metalloproteinases 3, 9, and 13 and prevents cartilage destruction during chronic reactivated streptococcal cell wall–induced arthritis
Authors: Koenders Marije I. , Kolls Jay K. , Oppers‐Walgreen Birgitte , Van Den Bersselaar Liduine , Joosten Leo A. B. , Schurr Jill R. , Schwarzenberger Paul , Van Den Berg Wim B. , Lubberts Erik 
Published: September 2005

AbstractObjectiveTo examine the role of interleukin‐17 receptor (IL‐17R) signaling in cartilage destruction and its interrelationship with synovial IL‐1 expression during chronic reactivated streptococcal cell wall (SCW)–induced arthritis.MethodsSCW arthritis was repeatedly induced in wild‐type (WT) and IL‐17R–deficient (IL‐17R–/–) mice. At different time points, joint inflammation was assessed by using calipers to measure joint swelling. On day 42, mice were killed, and knee joints were removed for histologic analysis. Quantitative polymerase chain reaction (PCR) analyses for different proinflammatory mediators and matrix metalloproteinases (MMPs) were performed on inflamed synovium from WT and IL‐17R–/– mice after 5 repeated injections of SCW fragments.ResultsIL‐17R signaling did not play a significant role in acute joint swelling induced by a single injection of SCW fragments directly into the joint. However, repeated local injections of SCW fragments into the knee joints of IL‐17R–/– mice resulted in fewer infiltrating cells in the joint compared with WT mice. Moreover, histologic analysis on day 42 revealed a significant suppression of the degree of chondrocyte death and an absence of cartilage surface erosion in IL‐17R–/– mice. Quantitative PCR analysis revealed impaired synovial expression of IL‐1, IL‐6, cyclooxygenase 2, stromelysin (MMP‐3), gelatinase B (MMP‐9), and collagenase 3 (MMP‐13) in IL‐17R–/– mice.ConclusionThese data show a critical role of IL‐17R signaling in driving the synovial expression of proinflammatory and catabolic mediators, such as IL‐1 and different MMPs, during progression from an acute, macrophage‐driven joint inflammation to a chronic, cartilage‐destructive, T cell–mediated synovitis. Prevention of IL‐17R signaling warrants consideration as a therapeutic target in chronic destructive arthritis.
Use of the plasma stromelysin (matrix metalloproteinase 3) concentration to predict joint space narrowing in knee osteoarthritis
Authors: Lohmander L. Stefan , Brandt Kenneth D. , Mazzuca Steven A. , Katz Barry P. , Larsson Staffan , Struglics André , Lane Kathleen A. 
Published: September 2005

AbstractObjectiveTo determine whether baseline or serial plasma concentrations of stromelysin (matrix metalloproteinase 3 [MMP‐3]) protein might distinguish subjects with progressive radiographic knee osteoarthritis (OA) from those with stable disease.MethodsSubjects were 120 women with unilateral knee OA who participated in a 30‐month randomized, placebo‐controlled trial of structure modification with doxycycline. Anteroposterior views of both knees in a semiflexed position were obtained at baseline, 16 months, and 30 months. Subjects were selected to obtain comparisons of plasma MMP‐3 levels between 60 progressors (21 taking doxycycline, 39 taking placebo) and 60 nonprogressors (30 taking doxycycline, 30 taking placebo) with respect to medial joint space narrowing (JSN) in the index knee. Each group consisted of 30 subjects who exhibited significant increases in knee pain. Blood samples were obtained semiannually for MMP‐3 assay.ResultsSubjects in the placebo group whose MMP‐3 concentration was in the upper tertile of the baseline distribution showed a 4‐fold increase in the odds of progression of JSN as compared with the lower tertile (odds ratio 4.12, P = 0.037). Baseline MMP‐3 levels were unrelated to knee pain. The within‐subject mean of serial MMP‐3 concentrations was associated with concurrent JSN in the placebo group over the 0–16‐month interval (b = 0.18 mm/SD increase in the mean MMP‐3, P < 0.01) and over the 16–30‐month interval (b = 0.15, P < 0.05). Similar evidence of concurrent validity was found in the placebo group for the maximum of intercurrent MMP‐3 values.ConclusionThe baseline MMP‐3 level was a significant predictor of JSN in this pilot study. Moreover, serial plasma MMP‐3 levels reflected concurrent JSN in the placebo group over the 30‐month period of observation.
B lymphocyte depletion therapy in children with refractory systemic lupus erythematosus
Authors: Marks Stephen D. , Patey Sue , Brogan Paul A. , Hasson Nathan , Pilkington Clarissa , Woo Patricia , Tullus Kjell 
Published: September 2005

AbstractObjectiveTo determine the safety and efficacy of B lymphocyte depletion therapy in patients with refractory childhood‐onset systemic lupus erythematosus (SLE).MethodsSeven patients (4 of whom were female), ages 7.7–16.1 years (median 14.8 years) with active SLE that was resistant to standard immunosuppressive agents were treated with B cell depletion. During a 2‐week period, patients received two 750‐mg/m2 intravenous infusions of rituximab, with intravenous cyclophosphamide (if they had not previously received this treatment) and high‐dose oral corticosteroids.ResultsPatients were followed up for a median of 1.0 years, and no serious adverse effects were noted. In all patients, the clinical symptoms and signs for which rituximab therapy was initiated were improved. There was significant improvement in the British Isles Lupus Assessment Group global scores, from a median score of 22 (range 14–37) at baseline to a median score of 6 (range 4–11) at followup (P = 0.002). In 2 patients with severe multisystem and life‐threatening disease unresponsive to standard therapy (including plasma exchange), renal replacement therapy was successfully withdrawn following B cell depletion therapy. These 2 patients have subsequently shown further significant improvement in renal function and proteinuria.ConclusionThis open‐label study demonstrates that targeted B cell depletion therapy can be a safe and efficacious addition to therapy with standard immunosuppressive agents in patients with refractory childhood SLE. The drugs used for treatment of childhood SLE need to be the most effective, least toxic agents, allowing normal growth and development.
A newly described hereditary cartilage debonding syndrome
Authors: Holderbaum D. , Malvitz T. , Ciesielski C. J. , Carson D. , Corr M. P. , Moskowitz R. W. 
Published: September 2005

AbstractObjectiveWe describe a hereditary chondropathy characterized by extreme cartilage friability and cartilage–bone debonding, which has not previously been described in the literature. We also describe initial studies into the molecular basis of this disorder.MethodsAffected family members had multiple shoulder, hip, and knee arthropathies, beginning in the preteen years and continuing into adulthood. Various diagnoses had been suggested, including spondyloepiphyseal dysplasia, multiple epiphyseal dysplasia, Legg‐Calvé‐Perthes disease, and Osgood‐Schlatter disease. The affected proband father, his 3 affected children, and unaffected family members provided blood samples, which were examined for single‐nucleotide polymorphisms (SNPs) in the chromosome 2 region that included the Frizzled‐related protein gene, a soluble Wnt protein signaling antagonist that influences bone and cartilage development.ResultsAll affected individuals showed clear similarities, including effusions, large loose bodies, and bubbling and delamination of the cartilage with exposure of subchondral bone. All affected individuals exhibited radiographic changes in the hip, showing femoral head flattening and secondary degenerative arthritis, accompanied by abnormalities in the physical properties of the cartilage that were evident upon arthroscopic examination. Two SNPs were identified in subjects with the hereditary cartilage debonding syndrome. Examination of the siblings and parents of the proband demonstrated, however, that both SNPs were present in the unaffected mother and in 2 of 4 unaffected siblings of the proband.ConclusionThe clinical findings reported here represent a newly defined clinical syndrome characterized by marked cartilage friability and osteochondral debonding. Because the SNPs are present in the general population, and because unaffected members of this family carry the SNPs, these polymorphisms alone are insufficient to result in the observed phenotype.
Synovial fibroblasts promote osteoclast formation by RANKL in a novel model of spontaneous erosive arthritis
Authors: Wu Yalei , Liu Jianzhong , Feng Xu , Yang PingAr , Xu Xin , Hsu Hui‐Chen , Mountz John D. 
Published: September 2005

AbstractObjectiveErosion of cartilage and bone is a hallmark of rheumatoid arthritis (RA). This study was undertaken to explore the roles of hyperproliferating synovial fibroblasts and macrophages in abnormal osteoclast formation, using the recently described BXD2 mouse model of RA.MethodsCell distribution in the joints was analyzed by immunohistochemistry, using tartrate‐resistant acid phosphatase (TRAP) staining to identify osteoclasts. To identify the defective cells in BXD2 mice, mouse synovial fibroblasts (MSFs) were cultured with bone marrow–derived macrophages. Osteoclast formation was assayed by TRAP staining and bone resorption pit assay, and the cytokine profiles of the MSFs and macrophages were determined by quantitative real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay.ResultsIn BXD2 mice, TRAP‐positive osteoclasts were found at sites of active bone erosion, in close proximity to hyperproliferating synovial fibroblasts. On coculture, MSFs from BXD2 mice, but not C57BL/6 mice, produced high levels of RANKL messenger RNA, induced macrophages to form osteoclasts, and actively eroded bone slices, through a mechanism(s) that could be blocked by pretreatment with osteoprotegerin. Although macrophages from BXD2 mice expressed higher basal levels of tumor necrosis factor α (TNFα), interleukin‐1β (IL‐1β), and IL‐6 than those from C57BL/6 mice, abnormal osteoclast formation was not due to enhanced sensitivity of the BXD2 mouse macrophages to RANKL. TNFα, produced by both BXD2 MSFs and BXD2 mouse macrophages, had a strong stimulatory effect on RANKL expression.ConclusionBXD2 MSFs produce RANKL and induce the development of osteoclasts from macrophages. The enhanced production of RANKL is possibly due to autocrine stimulation, together with paracrine stimulation by factors produced by macrophages.
Double‐blind, randomized, controlled clinical trial of clofazimine compared with chloroquine in patients with systemic lupus erythematosus
Authors: Bezerra Elaine Lira Medeiros , Vilar Maria José Pereira , da Trindade Neto Pedro Bezerra , Inoue Sato Emı´lia 
Published: September 2005

AbstractObjectiveTo evaluate the efficacy of clofazimine (CFZ) compared with chloroquine diphosphate (CDP) for the treatment of cutaneous involvement in systemic lupus erythematosus (SLE).MethodsA prospective, randomized, controlled, double‐blind clinical trial was carried out in SLE patients with active cutaneous lesions, of whom 16 were randomized to receive CFZ at 100 mg/day and 17 received CDP at 250 mg/day for 6 months. All drugs had a similar appearance to avoid identification. Both groups received broad‐spectrum sunscreens twice a day and the prednisone dose was kept stable during the study. Cutaneous lesions were evaluated by 2 blinded observers at baseline and at months 1, 2, 4, and 6.ResultsThirty‐three patients were randomized to a treatment group, of whom 27 completed 6 months of treatment. The groups were homogeneous and comparable in terms of demographic and clinical characteristics. Five CFZ‐treated patients and 1 CDP‐treated patient (P = 0.15) dropped out due to development of severe lupus flare. At the end of the study, 12 CFZ‐treated patients (75%) and 14 CDP‐treated patients (82.4%) had complete or near‐complete remission of skin lesions; intention‐to‐treat analysis showed no significant difference in the response rates between groups. Side effects, mainly skin and gastrointestinal events, were frequent in both groups, but no patients had to discontinue their treatment.ConclusionThese findings suggest that CFZ is equally as effective as CDP in controlling cutaneous lesions in SLE patients. However, we cannot exclude the possibility that the CFZ itself could be the cause of systemic lupus flare.
Investigating the Anomalous States of Knowledge hypothesis in a real‐life problem situation: A study of history and psychology undergraduates seeking information for a course essay
Authors: Cole Charles , Leide John , Beheshti Jamshid , Large Andrew , Brooks Martin 
Published: September 2005

AbstractThe authors present a study of the real‐life information needs of 59 McGill University undergraduates researching essay topics for either a history or psychology course, interviewed just after they had selected their essay topic. The interview's purpose was to transform the undergraduate's query from general topic terms, based on vague conceptions of their essay topic, to an information need‐based query. To chart the transformation, the authors investigate N. J. Belkin, R. N. Oddy, and H. M. Brooks' Anomalous States of Knowledge (ASK) hypothesis (1982a, 1982b), which links the user's ASK to a relevant document set via a common code based on structural facets. In the present study an interoperable structural code based on eight essay styles is created, then notions of structural facets compatible with a high‐impact essay structure are presented. The important findings of the study are: (a) the undergraduates' topic statements and terms derived from it do not constitute an effective information need statement because for most of the subjects in the study the topic terms conformed to a low‐impact essay style; (b) essay style is an effective interoperable structural code for charting the evolution of the undergraduate's knowledge state from ASK to partial resolution of the ASK in an information need statement.
The use of multi‐parameter flow cytometry to study the impact of limiting substrate, agitation intensity, and dilution rate on cell aggregation during Bacillus licheniformis CCMI 1034 aerobic continuous culture fermentations
Authors: da Silva Teresa Lopes , Reis Alberto , Kent Christopher A. , Roseiro J. Carlos , Hewitt Christopher J. 
Published: September 2005

AbstractThe main objective of this work was to establish those factors either physical (power input) or chemical (limiting substrate or dilution rate) that enhance cell aggregation (biofilm or floc formation) and cell physiological state during aerobic continuous cultures of Bacillus licheniformis. Glucose‐limited steady‐state continuous cultures growing at a dilution rate between 0.64 and 0.87/h and 1,000 rpm (mean specific energy dissipation rate ($\bar {\varepsilon} _T$) = 6.5 W/kg), led to the formation of a thin biofilm on the vessel wall characterized by the presence of a high proportion of healthy cells in the broth (after aggregate disruption by sonication) defined as having intact polarized cytoplasmic membranes. An increased $\bar {\varepsilon} _T$ (from 6.5 W/kg to 38 W/kg) was found to hinder cell aggregation under carbon limitation. The carbon recovery calculated from glucose indicated that additional extracellular polymer was being produced at dilution rates >0.87/h. B. licheniformis growth under nitrogen limitation led to floc formation which increased in size with dilution rate. Counter‐intuitively the flocs became more substantial with an increase in $\bar {\varepsilon} _T$ from 6.5 W/kg to 38 W/kg under nitrogen limitation. Indeed the best culture conditions for enhanced metabolically active cell aggregate formation was under nitrogen limitation at $\bar {\varepsilon} _T$ = 6.5 W/kg (leading to floc formation), and under carbon limitation at a dilution rate of between 0.64 and 0.87/h, at $\bar {\varepsilon} _T$ = 6.5 W/kg (leading to vessel wall biofilm formation). This information could be used to optimize culture conditions for improved cell aggregation and hence biomass separation, during thermophilic aerobic bioremediation processes. © 2005 Wiley Periodicals, Inc.
A simple and reliable method for the detection of sialylation in complex/hybrid‐type carbohydrate chains of glycoproteins by mixed lectins
Authors: Natsuki Jun , Machida Masayuki 
Published: September 2005

AbstractA practical and convenient method for discriminating between the presence and the absence of sialic acid in carbohydrate chains of glycoproteins was devised using paramagnetic beads and two lectins, Sambucus sieboldiana lectin (SSA) and Ricinus communis agglutinin (RCA120). The glycoproteins of transferrin or thyroglobulin were firstly captured to paramagnetic beads that were previously coated with corresponding antibody, and then the lectins of RCA120‐biotin and SSA‐FITC were bound to the glycoproteins on the paramagnetic beads. Finally, the fluorescence intensity of the beads was measured to determine the ratios of lectins RCA120‐biotin/Cy5‐streptavidin to SSA‐FITC. The mixed lectins method showed bigger difference of the ratios between the presence and the absence of sialic acid, indicating higher discrimination efficiency than the ordinary non‐mixed lectins method. Furthermore, statistical analysis by two‐side t‐test indicated that the mixed lectins method was more highly reliable than the ordinary non‐mixed lectins method in discriminating between the presence and the absence of sialic acid. The reaction with the two lectins can be performed in a single tube and readily automated taking advantage of the use of paramagnetic beads. © 2005 Wiley Periodicals, Inc.
Use of real‐time PCR for group‐specific quantification of aceticlastic methanogens in anaerobic processes: Population dynamics and community structures
Authors: Yu Youngseob , Kim Jaai , Hwang Seokhwan 
Published: September 2005

AbstractThe TaqMan quantitative PCR (QPCR) method was used to detect and quantify the 16S rRNA genes of aceticlastic methanogens at different taxonomic levels. Three different sets of primers coupled with a TaqMan probe for QPCR assays to detect the 16S rRNA genes of the order Methanosarcinales, as well as the families Methanosarcinaceae and Methanosaetaceae, were separately used. Using these primer and probe sets, the 16S rRNA genes of aceticlastic methanogens in samples from various anaerobic processes (i.e., nine pure cultures, batch experiment, and three different continuous processes including a full‐scale digester), were monitored and quantified by QPCR assays. A batch experiment cultivating a mixture of aceticlastic methanogens, was conducted to monitor their population dynamics. Using this group‐specific quantification method, the dynamics of a competition between two aceticlastic populations, as modulated by the acetate concentration, could well be described. The target 16S rRNA genes in environmental samples, collected from three different anaerobic processes treating sludge, cheese whey, and synthetic wastewaters, were additionally quantified. The quantified 16S rRNA gene concentrations for all samples successfully represented the community structures of the target methanogens, which were correlated accurately with the operational parameters of the anaerobic processes. It was also successful to demonstrate probe nesting of aceticlastic methanogens at the levels of order and family. © 2005 Wiley Periodicals, Inc.
Changes in the structural properties and rate of hydrolysis of cotton fibers during extended enzymatic hydrolysis
Authors: Wang Lushan , Zhang Yuzhong , Gao Peiji , Shi Dongxia , Liu Hongwen , Gao Hongjun 
Published: September 2005

AbstractAn extended enzymatic hydrolysis of cotton fibers by crude cellulase from Trichoderma pseudokoningii S‐38 is described with characterization of both the enzyme changes of activities and cellulose structure. The hydrolysis rates declined drastically during the early stage and then slowly and steadily throughout the whole hydrolysis process the same trend could be seen during the following re‐hydrolysis process. Morphological and structural changes to the fibers, such as swelling, frequent surface erosion, and variation in the packing and orientation of microfibrils, were investigated by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Observation of X‐ray diffraction and IR spectra suggests that the hydrolysis process results in a gradual increase in the relative intensity of the hydrogen bond network, and a gradual decrease in the apparent crystal size of cellulose. The Iα crystal phase was hydrolyzed more easily than was the Iβ crystal phase. Apart from the inactivation of CBHs activity, changes in the packing and arrangement of microfibrils and the structural heterogeneity of cellulose during hydrolysis could be responsible for the reduction in the rate of reaction, especially in its later stages. The results indicate that the enzymatic hydrolysis of cellulose occurs on the outer layer of the fiber surface and that, following this, the process continues in a sub‐layer manner. © 2005 Wiley Periodicals, Inc.
Platinum Complexes of Dibenzo[1,2]Dithiin, Dibenzo[1,2]Dithiin Oxides and Related Polyaromatic Hydrocarbon Ligands
Authors: Aucott Stephen M. , Kilian Petr , Robertson Stuart D. , Slawin Alexandra M. Z. , Woollins J. Derek 
Published: September 2005

AbstractThe synthesis of platinum bisphosphine complexes of biphenyl‐ 2,2′‐dichalcogenates and the oxides of dibenzo[1,2]dithiin and related ligand systems by oxidative addition to [Pt(PPh3)4] is reported. We also describe the synthesis of a new compound, dibenzothiophen‐4‐yldiselenide and its simple platinum complex (obtained by oxidative addition). All complexes have been fully characterised, principally by using multinuclear NMR spectroscopy and in six cases by means of single‐crystal X‐ray diffraction studies. The majority are simple S/S or Se/Se complexes, however the addition of dibenzo[1,2]dithiin trioxide to [Pt(PPh3)4] gives a bimetallic system, [Pt{2‐[S(O)],2′‐[S(O)2]‐biphen}(PPh3)]2, containing a central Pt2S2O2 core in which the ligand behaves as a tridentate S,S,O donor.