bluuebunny/crossref_metadata_2025 huggingface dataset:
Auditioning Betty in Mulholland Drive
Authors: Toles George
Published: October 2004

Abstract This essay argues that Betty's audition scene in Mulholland Drive is the Rosetta Stone for the mysteries of star acting in Hollywood film. By means of an almost moment-by-moment reconstruction of the audition segment, Toles demonstrates how our presumed ironic superiority to artifice and role playing is cunningly exchanged for a believer's faith in movie acting truth.
Male Melancholia and Martin Scorsese's The Age of Innocence
Authors: Nicholls Mark
Published: October 2004

Abstract Through an analysis of Martin Scorsese's The Age of Innocence, this article proposes a psychoanalytically based theory of male melancholia. Grounded in the cultural ambiguities of loss and masculinity, melancholia is revealed as an essential tool for reading Scorsese's film and for understanding representations of male desire in the cinema.
Adaptation
Authors: Hilderbrand Lucas
Published: October 2004

Abstract This review of Adaptation (2002) argues that the film productively narrativizes masturbation's myriad associations, pathologies, and, most importantly, possibilities for creative inspiration. The self-reflexive film presents writers as autoerotic fantasizers who suffer through malaise and self-doubt,and struggle to express themselves and to believe in what they are writing.
Monster's Ball
Authors: Mask Mia
Published: October 2004

Abstract More African Americans appear on network and cable television than ever before. Yet there are few quality dramatic roles for black actresses. The critical attention and public controversy surrounding Marc Forster's Monster's Ball (2001) demonstrated the existence of an audience for independent, art-house cinema featuring serious African-American characters. It's unfortunate that when read against the identity categories of race, gender, class, and region, Halle Berry's Leticia Musgrove seems to be a conflation of stereotypes: the sexual siren and the welfare queen.
Two Irreconcilable Conceptions of Rhetorical Proofs in Aristotle's Rhetoric
Authors: McAdon Brad
Published: October 2004

AbstractThis essay examines the inconsistencies in the discussion of proofs in Rhetoric 1.1 and 1.2. Recent commentators have attempted to reconcile these inconsistencies by claiming that ethos and pathos are to be understood as rational, inferential, or cognitive aspects of Aristotle's conception of rhetorical proof, thus linking the proofs in 1.2 to those in 1.1. In sharp contrast, I contend that the rift between the two conceptions of rhetorical proofs is even greater than most commentators acknowledge. I argue that there are two completely different conceptions of rhetorical proofs that cannot be reconciled in these two sections of the Rhetoric, that the inconsistencies are due to the tumultuous transmission and editorial history of the corpus Aristotelicum (and not to any of Aristotle's developmental views on rhetoric), and that the transmission and editorial history of the text needs to play a much more important role in our interpretation of the Rhetoric than it has hitherto.
Growth and aggregation of vaterite in seeded‐batch experiments
Authors: Andreassen Jens‐P. , Hounslow M. J.
Published: October 2004

Seeded‐batch crystallization experiments allowing study of the growth and aggregation of the Vaterite modification of calcium carbonate are reported. Results are reported for initial relative supersaturation (σ = S − 1) values in the range 1.66 to 6.70, stirrer speeds in the range 400 and 1200 rpm, and at temperatures of 25 and 40°C. It is found that in all cases the linear rate of growth of the particles is size independent and depends on relative supersaturation squared. The aggregation process is apparently size independent with a rate constant that is directly proportional to the instantaneous growth rate and decreases with increasing stirrer speed. The behavior of the aggregation rate constant is very well described by the model recently proposed by Liew et al., in which the efficiency of the aggregation process is predicted to depend only on the dimensionless strength of the particles and the nature of the flow field. It is concluded that Vaterite forms aggregates with crystalline bridges having an effective strength of approximately 25% of that of calcite or calcium oxalate monohydrate. The fitted parameter Lσ*/M50 takes on a value of 0.18 ± 0.02. The kinetics and associated model are capable of describing the evolving particle size distributions very well. Finally, a hypothesis is advanced to describe the aggregation of small inorganic crystals in supersaturated solutions. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2772–2782, 2004
Methane steam reforming by microporous catalytic membrane reactors
Authors: Tsuru Toshinori , Yamaguchi Koji , Yoshioka Tomohisa , Asaeda Masashi
Published: October 2004

Methane steam reforming, with and without added oxygen, was theoretically and experimentally investigated using microporous silica membranes, thus allowing the permeation of hydrogen as well as other gases in reactants and products. A simulation of catalytic membrane reactors was carried out for a cocurrent, isothermal, and plug‐flow–type membrane reactor with the selective permeation of hydrogen through microporous membranes. The effect of operating conditions on the conversion of methane and hydrogen production is discussed with the aid of two dimensionless numbers, the Damköhler number (Da) and the permeation number (θ). Methane conversion, XCH4, has approximately the same dependency on permeation number in terms of the permeability ratios of hydrogen over nitrogen, whereas the purity of hydrogen in the permeate increased with increasing hydrogen selectivity. Catalytic membrane reactors, consisting of a silica microporous layer and a Ni‐catalyst layer, were prepared. The permeability ratio of hydrogen over steam, α(H2/H2O), which ranged from 1 to 20, showed a relatively good correlation with that for helium over hydrogen, α(He/H2). Catalytic membrane reactors showing a hydrogen selectivity over nitrogen of 30–100, with hydrogen permeances of 0.5–3 × 10−7 mol m−2 s−1 Pa−1, were applied to the steam reforming of methane with and without the addition of oxygen. The reaction was carried out at 500°C, and the feed and permeate pressure were maintained at 100 and 20 kPa, respectively. Methane conversion, XCH4, increased up to approximately 0.8 beyond the equilibrium conversion of 0.44 by extracting hydrogen in permeate stream. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2794–2805, 2004
High resolution algorithms for multidimensional population balance equations
Authors: Gunawan Rudiyanto , Fusman Irene , Braatz Richard D.
Published: October 2004

Population balance equations have been used to model a wide range of processes including polymerization, crystallization, cloud formation, and cell dynamics. Rather than developing new algorithms specific to population balance equations, it is proposed to adapt the high‐resolution finite volume methods developed for compressible gas dynamics, which have been applied to aerodynamics, astrophysics, detonation waves, and related fields where shock waves occur. High‐resolution algorithms are presented for simulating multidimensional population balance equations with nucleation and size‐dependent growth rates. For sharp distributions, these high‐resolution algorithms can achieve improved numerical accuracy with orders‐of‐magnitude lower computational cost than other finite difference and finite volume algorithms. The algorithms are implemented in the ParticleSolver software package, which is applied to batch and continuous processes with one and multiple internal coordinates. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2738–2749, 2004
Modeling for size reduction of agglomerates in nanoparticle fluidization
Authors: Matsuda Satoru , Hatano Hiroyuki , Muramoto Tomoya , Tsutsumi Atsushi
Published: October 2004

Nanoparticle fluidization was studied in a centrifugal fluidized bed (CenFB) with variable gravitational acceleration (Gg) conditions. Agglomerate size variation in CenFB nanoparticles (7 nm) was examined with G and fluidization time. With increasing fluidization time, the agglomerate size was found to decrease and reach an equilibrium value after several hours. Higher G reduced agglomerate size. To elucidate these phenomena, a comprehensive model was developed based on the energy balance model with respect to energy consumption for disintegration of agglomerates. Experimental results showed good agreement with the proposed model. Effects of high G on agglomerate fluidization are clarified as follows. The critical minimum size of agglomerates, which is the agglomerate size estimated by the force balance model, is reduced by high G. Attainable energy for disintegration of agglomerates is increased, leading to decreased agglomerate size. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2763–2771, 2004
Prediction of rolling bed motion in rotating cylinders
Authors: Mellmann Jochen , Specht Eckehard , Liu Xiaoyan
Published: October 2004

A mathematical model for the range of rolling bed motion has been developed to calculate the transverse solids motion in rotating cylinders. It is based on mass and momentum balances with physically specified and hence known initial conditions. The behavior of the bed material need only be described by two measurable parameters, the dynamic angle of repose and the angle of slope at the start of the boundary line (interface between the cascading layer and the plug flow region). The shape of the boundary line, the thickness of the cascading layer, the mass flow rate, and the velocity at the surface can be predicted as a function of rotation speed, filling degree, and cylinder diameter. No fitting parameter is needed for the calculation. To verify the model, experiments were carried out for many bed materials and rotating cylinder conditions. A correlation for the angle of slope at the start of the boundary line is given. The calculated results of the model are then compared to our own measurements and those reported in the literature. It is shown that the model agrees relatively well with the experiments. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2783–2793, 2004
Association between spine disc degeneration and type II collagen degradation in postmenopausal women: The OFELY study
Authors: Garnero Patrick , Sornay‐Rendu Elisabeth , Arlot Monique , Christiansen Claus , Delmas Pierre D.
Published: October 2004

Objective

To investigate whether radiologic spine disc degeneration is associated with increased type II collagen (CII) degradation products in the urine of postmenopausal women, independently of radiologic knee osteoarthritis (OA) and clinical hand OA.

Methods

The study group comprised 324 postmenopausal women ages 58–94 years who had no treatment or disease that could alter bone metabolism. Lateral radiographs of the thoracic and lumbar spine were obtained in each woman and scored for disc space narrowing (DSN) and osteophytes. Fixed‐flexion posteroanterior radiographs of the knee were obtained to assess femorotibial knee OA. In all women, hand OA was assessed by clinical examination, and the level of urinary C‐terminal crosslinking telopeptide of CII (CTX‐II), a biologic marker of CII degradation, was measured.

Results

The prevalences of radiographic lumbar and thoracic spine disc degeneration, knee OA, and clinical hand OA were 84%, 88%, 35%, and 58%, respectively. After adjustment for age and body mass index (BMI), patients with lumbar spine DSN grade ≥1 had, on average, 34% higher CTX‐II levels compared with the other women (P = 0.0005), whereas no association was observed with lumbar spine osteophytes. No significant association between thoracic spine DSN or osteophytes and urinary CTX‐II levels was observed. Multivariate analysis of variance showed that, after adjustment for age and BMI, lumbar spine DSN (P = 0.0049), knee OA (P = 0.0055), and clinical hand OA (P = 0.0060) were, independently of each other, associated with CTX‐II levels. Thus, patients with lumbar spine DSN, knee OA, and clinical hand OA had CTX‐II levels 80% higher (P < 0.0001 after adjustment for age and BMI) than those of patients with no lumbar spine DSN, no radiologic knee OA, and no clinical hand OA.

Conclusion

Postmenopausal women with lumbar spine disc degeneration are characterized by increased CII degradation. The contribution of lumbar spine DSN to CII degradation was similar to, and independent of, the contribution of radiologic knee OA or clinical hand OA. Lumbar spine disc degeneration in elderly patients should be assessed when analyzing levels of CTX‐II in studies of knee, hip, and hand OA.
Work above shoulder level and degenerative alterations of the rotator cuff tendons: A magnetic resonance imaging study
Authors: Svendsen Susanne Wulff , Gelineck John , Mathiassen Svend Erik , Bonde Jens Peter , Frich Lars Henrik , Stengaard‐Pedersen Kristian , Egund Niels
Published: October 2004

Objective

To determine whether work performed with the arms in a highly elevated position is associated with alterations in the rotator cuff tendons as assessed by magnetic resonance imaging (MRI).

Methods

A cross‐sectional study was performed in a historical cohort of male machinists, car mechanics, and house painters. The participants were right‐handed, ages 40–50 years, and had been employed in their trades for not less than 10 years. Seventy‐one percent of invited subjects participated (136 of 192). Lifetime upper arm elevation was assessed by direct measurements combined with individual work histories obtained by questionnaire and from registry data. Supraspinatus tendinopathy was evidenced by MRI signal intensity changes and morphologic alterations. Infraspinatus and subscapularis tendinopathy were also assessed. Additional outcomes were acromioclavicular joint degeneration and humeral head cysts. The MRI findings were evaluated by radiologists who were blinded to exposure status and symptoms.

Results

An exposure–response relationship was found between lifetime upper arm elevation and supraspinatus tendinopathy, with an age‐adjusted odds ratio of 1.27 (95% confidence interval 1.02–1.60) for a 5‐month increase in the total number of full‐time working months spent with the arm elevated >90°.

Conclusion

Work with the arms in a highly elevated position is associated with MRI‐diagnosed alterations in the supraspinatus tendon. By demonstrating the first part of a possible biologic pathway, the study corroborates the work‐relatedness of rotator cuff disorders.
Characterization of pristane‐induced arthritis, a murine model of chronic disease: Response to antirheumatic agents, expression of joint cytokines, and immunopathology
Authors: Patten Christopher , Bush Katherine , Rioja Inma , Morgan Rebecca , Wooley Paul , Trill John , Life Paul
Published: October 2004

Objective

To characterize chronic murine pristane‐induced arthritis (PIA) with regard to the response to antirheumatic agents, expression levels of proinflammatory cytokines, and immunopathologic features.

Methods

Male DBA/1 mice were injected intraperitoneally with pristane oil to induce a chronic polyarthritis, which was monitored by visual scoring. Serum antibody and splenocyte responses to a panel of putative joint‐derived autoantigens were measured. Whole paws were evaluated postmortem for changes in the levels of proinflammatory cytokines tumor necrosis factor α (TNFα), interleukin‐1β (IL‐1β), and IL‐6 by enzyme‐linked immunosorbent assay, and standard histopathology techniques were used to determine joint structural changes. Therapeutic studies were performed for up to 8 weeks of dosing with prednisolone, methotrexate, 3 nonsteroidal antiinflammatory drugs (celecoxib, diclofenac, and indomethacin), a p38 MAPK inhibitor, SB242235, and human soluble TNF receptor (sTNFR; etanercept) and murine sTNFR fusion proteins.

Results

Antibody and cellular responses to the putative joint autoantigens revealed a broad extent of autoimmunity in PIA. TNFα, IL‐1β, and IL‐6 were all persistently up‐regulated in PIA joints. Prednisolone, methotrexate, celecoxib, indomethacin, and SB242235 all significantly reduced the arthritis scores. Etanercept was ineffective in reducing the arthritis scores, whereas murine sTNFR produced a significant, but nonsustained, benefit. Only prednisolone significantly reduced the expression of TNFα, IL‐1β, and IL‐6 in the joints. Prednisolone and methotrexate demonstrated the most effective joint protection.

Conclusion

We have markedly extended the characterization of PIA as a murine model of chronic inflammatory arthritis by demonstrating cellular and humoral autoantigenicity, elevation of clinically precedented joint cytokines, and variation in the response to several antirheumatic therapies. PIA offers significant potential for the long‐term study of immunopathologic mechanisms and novel therapies in rheumatoid arthritis.
Multisequence magnetic resonance imaging study of neuropsychiatric systemic lupus erythematosus
Authors: Bosma G. P. Th. , Steens S. C. A. , Petropoulos Helen , Admiraal‐Behloul Faiza , van den Haak A. , Doornbos J. , Huizinga T. W. J. , Brooks William M. , Harville Aaron , Sibbitt Wilmer L. , van Buchem M. A.
Published: October 2004

Objective

To investigate the relationship between magnetization transfer imaging (MTI), diffusion‐weighted imaging (DWI), proton magnetic resonance spectroscopy (H‐MRS), and T2 relaxometry findings in patients with primary neuropsychiatric systemic lupus erythematosus (NPSLE).

Methods

The study group consisted of 24 female patients (mean age 36 years [range 23–65]) who had had a variety of neuropsychiatric symptoms that were judged to be due to NPSLE according to the criteria of the American College of Rheumatology. Patients with current active disease were excluded from participation. Quantitative MTI, DWI, H‐MRS, and T2 relaxometry data were acquired in all patients, and the correlation coefficients were calculated.

Results

MTI results reflecting a decrease in homogeneity of cerebral parenchyma correlated significantly with H‐MRS results representing axonal damage. MTI results also correlated significantly with DWI results reflecting increased diffusivity in the cerebral parenchyma. Finally, MTI results reflecting decreased cerebral homogeneity correlated significantly with increased T2 relaxation time, associated with either edema or gliosis. Increased T2 relaxation time correlated significantly with DWI results reflecting increased diffusivity. With the exception of the correlation between H‐MRS and MTI findings, there was no significant correlation between H‐MRS results and any other parameter.

Conclusion

The selected study parameters represent different biologic features in the human brain and can be informative with regard to different pathologic processes in NPSLE. The demonstrated associations between MTI, DWI, H‐MRS, and T2 data in patients with a history of NPSLE suggest that there is one pathogenesis and/or common neuropathologic outcome in NPSLE despite differences in clinical presentation.
Antigen‐specific immunomodulation of collagen‐induced arthritis with tumor necrosis factor–stimulated dendritic cells
Authors: van Duivenvoorde Leonie M. , Louis‐Plence Pascale , Apparailly Florence , van der Voort Ellen I. H. , Huizinga Tom W. J. , Jorgensen Christian , Toes René E. M.
Published: October 2004

Objective

Dendritic cells (DCs) are crucial for the initiation of T cell immunity and therefore play an important role in the initiation and regulation of immune responses in arthritis. Full mobilization of effector T cells depends on the proper maturation of DCs. Current evidence indicates that the type of T cell response induced is crucially dependent on the activation status of the DCs. In this study, we explored the immunologic effects of differentially matured DCs on the development of collagen‐induced arthritis (CIA).

Methods

Bone marrow–derived DCs were cultured in the presence of granulocyte–macrophage colony‐stimulating factor (GM‐CSF). Before immunization with bovine type II collagen (CII) protein, mice were repeatedly injected with DCs that had been pulsed with CII. Immature, semimature, or fully mature DCs were injected. Mice were boosted on day 21 after CII immunization, and the disease course was monitored.

Results

While vaccination with immature or lipopolysaccharide‐activated DCs had no significant effect on the disease course, administration of antigen‐loaded, tumor necrosis factor (TNF)–modulated DCs propagated in GM‐CSF with or without interleukin‐4 resulted in a delayed onset of arthritis and a lower clinical score. The response was antigen‐specific, since TNF‐treated DCs pulsed with a control antigen did not modify the disease course. A specific decrease in the collagen‐specific “Th1‐associated” IgG2a response was observed, whereas IgG1 titers were unaffected.

Conclusion

CIA can be prevented through vaccination with TNF‐matured DCs in an antigen‐specific manner. These findings provide a rationale for immunotherapy using DCs in rheumatoid arthritis.
Direct binding of anti–DNA topoisomerase I autoantibodies to the cell surface of fibroblasts in patients with systemic sclerosis
Authors: Hénault Jill , Tremblay Mélanie , Clément Isabelle , Raymond Yves , Senécal Jean‐Luc
Published: October 2004

Objective

Fibroblasts play a crucial role in the development of systemic sclerosis (SSc), and antifibroblast antibodies (AFAs) capable of inducing a proinflammatory phenotype in fibroblasts have been detected in the sera of SSc patients. This study examined the prevalence of AFAs in SSc and other diseases and the possible correlation between AFAs and known antinuclear antibody specificities in SSc patients.

Methods

Sera from 99 patients with SSc, 123 patients with other autoimmune and nonautoimmune diseases, and 30 age‐ and sex‐matched healthy controls were examined. AFA prevalence was assessed by flow cytometry and further characterized by indirect immunofluorescence, enzyme‐linked immunosorbent assay (ELISA), and immunoblotting. Anti–topoisomerase I (anti–topo I) from SSc sera were purified by affinity chromatography on topo I.

Results

AFAs were more common in SSc patients (26.3%) than in any other disease groups studied. The presence of AFA was significantly associated with pulmonary involvement and death. AFA‐positive sera from SSc patients bound to all human and rodent fibroblasts tested, but not to human primary endothelial cells or smooth muscle cells. All SSc AFAs strongly reacted with topo I by ELISA and immunoblotting. The binding intensity of SSc AFAs correlated strongly with reactivity against topo I on immunoblots of fibroblast extracts and with the immunofluorescence pattern typical of anti–topo I on permeabilized cells. Total IgG and affinity‐purified anti–topo I from AFA‐positive SSc sera were found to react with the surface of unpermeabilized fibroblasts by flow cytometry as well as by immunofluorescence and confocal microscopy.

Conclusion

This is the first report establishing that AFAs in SSc are strongly correlated with anti–topo I and, furthermore, that anti–topo I antibodies themselves display AFA activity by reacting with determinants at the fibroblast surface.
Treatment of murine lupus using nucleosomal T cell epitopes identified by bone marrow–derived dendritic cells
Authors: Suen Jau‐Ling , Chuang Ya‐Hui , Tsai Bor‐Yu , Yau Peter M. , Chiang Bor‐Luen
Published: October 2004

Objective

Systemic lupus erythematosus (SLE) is characterized by the existence of a heterogeneous group of autoantibodies directed against intact nuclear structures, such as nucleosomes. The most prominent of these autoantibodies are those directed against double‐stranded DNA (dsDNA) and histones. The majority are of the IgG isotype and show affinity maturation, both of which are known hallmarks of T cell help. Much evidence suggests that the nucleosome is a major candidate autoantigen in SLE. In this study, a novel strategy was used to identify the critical CD4+ T cell autoepitopes in nucleosomes. In addition, peptide‐based therapy was then performed in a lupus animal model.

Methods

Bone marrow (BM)–derived dendritic cells (DCs) were used to examine the self–T cell responses against nucleosomes and to characterize the T cell epitope(s) of nucleosomes in (NZB × NZW)F1 (BWF1) mice.

Results

Several potential auto–T cell epitopes of core histone proteins (H2A, H2B, H3, and H4) were identified. Nucleosome‐pulsed BM‐derived DCs elicited release of interleukin‐4 and interferon‐γ, representing a Th0 (i.e., mixed Th1 and Th2) pattern of cytokine production. In addition, intradermal immunization of BWF1 mice with the H3111–130 peptide not only suppressed the level of anti‐dsDNA and anti–single‐stranded DNA IgG, but also significantly delayed the progress of glomerulonephritis in lupus‐prone BWF1 mice.

Conclusion

These results will help in understanding how pathogenic autoimmune responses develop in spontaneous SLE. This may potentially open the way to T cell–based immunotherapy for lupus.
Development and validation of the health assessment questionnaire II: A revised version of the health assessment questionnaire
Authors: Wolfe Frederick , Michaud Kaleb , Pincus Theodore
Published: October 2004

Objective

The Health Assessment Questionnaire (HAQ) has become the most common tool for measuring functional status in rheumatology. However, the HAQ is long (34 questions, including 20 concerning activities of daily living and 14 relating to the use of aids and devices) and somewhat burdensome to score, has some floor effects, and has psychometric problems relating to linearity and confusing items. We undertook this study to develop and validate a revised version of the HAQ (the HAQ‐II).

Methods

Using Rasch analysis and a 31‐question item bank, including 20 HAQ items, the 10‐item HAQ‐II was developed. Five original items from the HAQ were retained. We studied the HAQ‐II in 14,038 patients with rheumatic disease over a 2‐year period to determine its validity and reliability.

Results

The HAQ‐II was reliable (reliability of 0.88, compared with 0.83 for the HAQ), measured disability over a longer scale than the HAQ, and had no nonfitting items and no gaps. Compared with the HAQ, modified HAQ, and Medical Outcomes Study Short Form 36 physical function scale, the HAQ‐II was as well correlated or better correlated with clinical and outcome variables. The HAQ‐II performed as well as the HAQ in a clinical trial and in prediction of mortality and work disability. The mean difference between the HAQ and HAQ‐II scores was 0.02 units.

Conclusion

The HAQ‐II is a reliable and valid 10‐item questionnaire that performs at least as well as the HAQ and is simpler to administer and score. Conversion from HAQ to HAQ‐II and from HAQ‐II to HAQ for research purposes is simple and reliable. The HAQ‐II can be used in all places where the HAQ is now used, and it may prove to be easier to use in the clinic.
A gene–environment interaction between smoking and shared epitope genes in HLA–DR provides a high risk of seropositive rheumatoid arthritis
Authors: Padyukov Leonid , Silva Camilla , Stolt Patrik , Alfredsson Lars , Klareskog Lars
Published: October 2004

Objective

The main genetic risk factor for rheumatoid arthritis (RA) is the shared epitope (SE) of HLA–DR, while smoking is an important environmental risk factor. We studied a potential gene–environment interaction between SE genes and smoking in the etiology of the 2 major subgroups of RA: rheumatoid factor (RF)–seropositive and RF‐seronegative disease.

Methods

A population‐based case–control study involving incident cases of RF‐seropositive and RF‐seronegative RA (858 cases and 1,048 controls) was performed in Sweden. Cases and controls were classified according to their cigarette smoking status and HLA–DRB1 genotypes. The relative risk of developing RA was calculated for different gene/smoking combinations and was compared with the relative risk in never smokers without SE genes.

Results

The relative risk of RF‐seropositive RA was 2.8 (95% confidence interval [95% CI] 1.6–4.8) in never smokers with SE genes, 2.4 (95% CI 1.3–4.6) in current smokers without SE genes, and 7.5 (95% CI 4.2–13.1) in current smokers with SE genes. Smokers carrying double SE genes displayed a relative risk of RF‐seropositive RA of 15.7 (95% CI 7.2–34.2). The interaction between smoking and SE genes was significant, as measured by the attributable proportion due to interaction, which was 0.4 (95% CI 0.2–0.7) for smoking and any SE, and 0.6 (95% CI 0.4–0.9) for smoking and a double SE. Neither smoking nor SE genes nor the combination of these factors increased the risk of developing RF‐seronegative RA.

Conclusion

The disease risk of RF‐seropositive RA associated with one of the classic genetic risk factors for immune‐mediated diseases (the SE of HLA–DR) is strongly influenced by the presence of an environmental factor (smoking) in the population at risk.
Outcomes of hospitalizations for myocardial infarctions and cerebrovascular accidents in patients with systemic lupus erythematosus
Authors: Ward Michael M.
Published: October 2004

Objective

Patients with systemic lupus erythematosus (SLE) have increased risks of acute myocardial infarction (AMI) and cerebrovascular accident (CVA), but it is not known whether they have worse outcomes after AMI or CVA compared with patients without SLE. This study compared in‐hospital mortality, length of stay, and other measures of severity (congestive heart failure or need for coronary artery bypass grafting after AMI; discharge to a skilled nursing facility after CVA) between patients with SLE and patients without SLE who were hospitalized for AMI or CVA.

Methods

Data on all patients hospitalized in California with either AMI or CVA from 1996 to 2000 were abstracted from a state hospitalization database. Outcomes after AMI were compared between 519 patients with SLE and 214,771 patients without SLE, and outcomes after CVA were compared between 905 patients with SLE and 293,326 patients without SLE. Analyses were performed separately for men and women.

Results

Among women with AMI, there were no differences in the risk of in‐hospital mortality, long length of stay, or congestive heart failure between patients with SLE and those without SLE, but women with SLE were less likely to undergo coronary artery bypass grafting. Outcomes after AMI did not differ between men with SLE and men without SLE. Among women with CVA, there were no differences in outcomes between patients with SLE and patients without SLE. Men with SLE were almost twice as likely to have a long length of stay after CVA than were men without SLE.

Conclusion

Outcomes after AMI and CVA are generally similar between patients with SLE and those without SLE.
Matrix metalloproteinase 12–dependent cleavage of urokinase receptor in systemic sclerosis microvascular endothelial cells results in impaired angiogenesis
Authors: D'Alessio Silvia , Fibbi Gabriella , Cinelli Marina , Guiducci Serena , Del Rosso Angela , Margheri Francesca , Serratì Simona , Pucci Marco , Kahaleh Bashar , Fan Pansheng , Annunziato Francesco , Cosmi Lorenzo , Liotta Francesco , Matucci‐Cerinic Marco , Del Rosso Mario
Published: October 2004

Objective

Defective angiogenesis, resulting in tissue ischemia, is particularly prominent in the diffuse form of systemic sclerosis (SSc). The present study was undertaken to identify possible differences between normal and SSc microvascular endothelial cells (MVECs) in the expression of the cell‐associated urokinase‐type plasminogen activator (uPA)/uPA receptor (uPAR) system, which is critical in the angiogenic process.

Methods

MVECs were isolated from the dermis of healthy individuals and from the dermis of patients with diffuse SSc. The uPA/uPAR system was examined at the protein and messenger RNA levels. Angiogenesis was assayed on Matrigel‐coated porous filters and plates to evaluate cell proliferation, invasion, and capillary morphogenesis. Cleavage of uPAR and the activity of matrix metalloproteinase 12 (MMP‐12) were evaluated by Western blotting.

Results

Compared with MVECs from healthy skin, MVECs from SSc patients showed higher expression of uPAR. However, in SSc MVECs, uPAR undergoes truncation between domain 1 and domain 2, as shown by flow cytometry, enzyme‐linked immunosorbent assay, and Western blotting, a cleavage that is known to impair uPAR functions. These properties of SSc MVECs were associated with poor spontaneous and uPA‐dependent invasion, proliferation, and capillary morphogenesis. The uPAR cleavage occurring in SSc MVECs was associated with overexpression of MMP‐12. SSc MVEC–conditioned medium impaired uPA‐dependent proliferation and invasion as well as capillary morphogenesis in normal MVECs in vitro. Both a general hydroxamate inhibitor of MMP activity and anti–MMP‐12 antibodies restored this SSc MVEC–induced impaired functioning.

Conclusion

Overproduction of MMP‐12 by SSc MVECs accounts for the cleavage of uPAR and the impairment of angiogenesis in vitro and may contribute to reduced angiogenesis in SSc patients.
A six‐month followup of a randomized trial comparing the efficacy of a lateral‐wedge insole with subtalar strapping and an in‐shoe lateral‐wedge insole in patients with varus deformity osteoarthritis of the knee
Authors: Toda Yoshitaka , Tsukimura Noriko
Published: October 2004

Objective

To assess the effect of a lateral‐wedge insole with elastic strapping of the subtalar joint on the femorotibial angle in patients with varus deformity of the knee.

Methods

The efficacy of a wedged insole with subtalar straps and that of a traditional wedged insole shoe insert were compared. Sixty‐six female outpatients with knee osteoarthritis (OA) were randomized (according to birth date) to be treated with either the strapped or the traditional inserted insole. Standing radiographs with unilateral insole use were used to analyze the femorotibial angles for each patient. In both groups, the baseline and 6‐month visual analog scale (VAS) scores for subjective knee pain and the Lequesne index scores for knee OA were compared.

Results

The 61 patients who completed the 6‐month study were evaluated. At baseline, there was no significant difference in the femorotibial angle (P = 0.66) and the VAS score (P = 0.75) between the 2 groups. At the 6‐month assessment, the 29 subjects wearing the subtalar‐strapped insole demonstrated a significantly decreased femorotibial angle (P < 0.0001) and significantly improved VAS scores (P = 0.001) and Lequesne index scores (P = 0.033) compared with their baseline assessments. These significant differences were not observed in the 32 subjects assigned to the traditional shoe‐inserted wedged insole.

Conclusion

These results suggest that an insole with a subtalar strap maintained the valgus correction of the femorotibial angle in patients with varus knee OA for 6 months, indicating longer‐term clinical improvement with the strapped insert compared with the traditional insert.
Expression of mitogen‐activated protein kinase phosphatase 1, a negative regulator of the mitogen‐activated protein kinases, in rheumatoid arthritis: Up‐regulation by interleukin‐1β and glucocorticoids
Authors: Toh Myew‐Ling , Yang Yuan , Leech Michelle , Santos Lanie , Morand Eric F.
Published: October 2004

Objective

Mitogen‐activated protein kinases (MAPKs) are activated by proinflammatory stimuli. MAPK phosphatases (MKPs), in particular MKP‐1, have been identified as endogenous negative regulators of MAPK activation. Since MAPKs are known to be important in rheumatoid arthritis (RA) synoviocyte activation, this study assessed the expression, regulation, and function of MKP‐1 in RA.

Methods

MKP‐1 expression was measured by Western blotting (WB) and real‐time polymerase chain reaction (PCR). RA fibroblast‐like synoviocytes (FLS) were treated with interleukin‐1β (IL‐1β), tumor necrosis factor α, fetal calf serum, and dexamethasone. Expression of MAPKs in RA FLS was analyzed by WB using phosphospecific antibodies, while IL‐6 expression was assessed by real‐time PCR.

Results

MKP‐1 protein and messenger RNA were detected in cultured RA FLS. IL‐1β rapidly up‐regulated MKP‐1, coinciding with reciprocal down‐regulation of ERK, JNK, and p38 MAPK phosphorylation. Dexamethasone rapidly and sustainably up‐regulated MKP‐1, and this also coincided with down‐regulation of ERK, JNK, and p38 MAPK phosphorylation. In addition, dexamethasone augmented IL‐1β–induced up‐regulation of MKP‐1, and this was associated with inhibition of ERK, JNK, and p38 MAPK phosphorylation and IL‐6 expression. Dexamethasone had no effect on the phosphorylation of upstream kinases such as MEKK‐3/6. In the presence of glucocorticoid (GC) receptor antagonist RU 486, the dexamethasone‐mediated up‐regulation of MKP‐1 was impaired. Moreover, inhibition of MKP‐1 expression impaired dexamethasone‐mediated inhibition of MAPK phosphorylation.

Conclusion

This study demonstrates the expression of MKP‐1 in RA FLS. Cytokine and GC regulation of MKP‐1 may be important in determining the magnitude of the inflammatory response in RA that is mediated via MAPKs. The effects of GCs in RA may be mediated, in part, via GC receptor–dependent up‐regulation of MKP‐1.
Histone deacetylase inhibitor suppression of autoantibody‐mediated arthritis in mice via regulation of p16INK4a and p21WAF1/Cip1 expression
Authors: Nishida Keiichiro , Komiyama Takamitsu , Miyazawa Shin‐ichi , Shen Zheng‐Nan , Furumatsu Takayuki , Doi Hideyuki , Yoshida Aki , Yamana Jiro , Yamamura Masahiro , Ninomiya Yoshihumi , Inoue Hajime , Asahara Hiroshi
Published: October 2004

Objective

To examine whether depsipeptide (FK228), a histone deacetylase (HDA) inhibitor, has inhibitory effects on the proliferation of synovial fibroblasts from rheumatoid arthritis (RA) patients, and to examine the effects of systemic administration of FK228 in an animal model of arthritis.

Methods

Autoantibody‐mediated arthritis (AMA) was induced in 19 male DBA/1 mice (6–7 weeks old); 10 of them were treated by intravenous administration of FK228 (2.5 mg/kg), and 9 were used as controls. The effects of FK228 were examined by radiographic, histologic, and immunohistochemical analyses and arthritis scores. RA synovial fibroblasts (RASFs) were obtained at the time of joint replacement surgery. In vitro effects of FK228 on cell proliferation were assessed by MTT assay. Cell morphology was examined by light and transmission electron microscopy. The effects on the expression of the cell cycle regulators p16INK4a and p21WAF1/Cip1 were examined by real‐time polymerase chain reaction and Western blot analysis. The acetylation status of the promoter regions of p16INK4a and p21WAF1/Cip1 were determined by chromatin immunoprecipitation assay.

Results

A single intravenous injection of FK228 (2.5 mg/ml) successfully inhibited joint swelling, synovial inflammation, and subsequent bone and cartilage destruction in mice with AMA. FK228 treatment induced histone hyperacetylation in the synovial cells and decreased the levels of tumor necrosis factor α and interleukin‐1β in the synovial tissues of mice with AMA. FK228 inhibited the in vitro proliferation of RASFs in a dose‐dependent manner. Treatment of cells with FK228 induced the expression of p16INK4a and up‐regulated the expression of p21WAF1/Cip1. These effects of FK228 on p16INK4a and p21WAF1/Cip1 were related to the acetylation of the promoter region of the genes.

Conclusion

Our findings strongly suggest that systemic administration of HDA inhibitors may represent a novel therapeutic target in RA by means of cell cycle arrest in RASFs via induction of p16INK4a expression and increase in p21WAF1/Cip1 expression.
Diphosphines with Expandable Bite Angles: Highly Active Ethylene Dimerisation Catalysts Based on Upper Rim, Distally Diphosphinated Calix[4]arenes
Authors: Lejeune Manuel , Sémeril David , Jeunesse Catherine , Matt Dominique , Peruch Frédéric , Lutz Pierre J. , Ricard Louis
Published: October 2004

The binding properties of two large diphosphines, cone‐5,17‐dibromo‐11,23‐bis(diphenylphosphino)‐25,26,27,28‐tetrapropoxycalix[4]arene (1) and cone‐5,17‐bis(diphenylphosphino)‐25,26,27,28‐tetrapropoxycalix[4]arene (2) toward NiII centres have been investigated. Whatever the starting complex, NiBr2 or [NiCp]BF4, quantitative formation of a chelate complex was observed, illustrating the preorganisation of the ligands. An X‐ray structure determination was carried out for [NiCp⋅1]BF4 which revealed that the nickel atom is positioned to one side of the calixarene axis, the PNiP plane being roughly parallel to the calixarene reference plane. The molecule has C1 symmetry in the solid state, a feature which is also observed in solution at low temperature. As shown by variable‐temperature 1H and 31P NMR studies, the complex undergoes two distinct motions: 1) a fan‐like swinging of the coordination plane which displaces the metal from one side of the calixarene axis to the other, a motion during which the PNiP angle is likely to undergo a significant enlargement; 2) a rapid oscillation of each PPh2 unit about the corresponding NiP bond. In the latter dynamics the two endo‐oriented PPh rings alternately occupy the calixarene entry. The two flexible ligands were assessed in ethylene oligomerisation. Activation with methylaluminoxane of the paramagnetic complexes [NiBr2⋅(1 or 2)] afforded highly active ethylene dimerisation catalysts, with turnover frequencies up to 106 (mol C2H4) (mol Ni)−1 h−1. The selective formation of 1‐butene can be rationally controlled by using low catalyst concentrations.
Sphingosine‐1‐phosphate plays a role in the suppression of lateral pseudopod formation during Dictyostelium discoideum cell migration and chemotaxis
Authors: Kumar Akhilesh , Wessels Deborah , Daniels Karla J. , Alexander Hannah , Alexander Stephen , Soll David R.
Published: October 2004

Sphingosine‐1‐phosphate (S‐1‐P) is a bioactive lipid that plays a role in diverse biological processes. It functions both as an extracellular ligand through a family of high‐affinity G‐protein‐coupled receptors, and intracellularly as a second messenger. A growing body of evidence has implicated S‐1‐P in controlling cell movement and chemotaxis in cultured mammalian cells. Mutant D. discoideum cells, in which the gene encoding the S‐1‐P lyase had been specifically disrupted by homologous recombination, previously were shown to be defective in pseudopod formation, suggesting that a resulting defect might exist in motility and/or chemotaxis. To test this prediction, we analyzed the behavior of mutant cells in buffer, and in both spatial and temporal gradients of the chemoattractant cAMP, using computer‐assisted 2‐D and 3‐D motion analysis systems. Under all conditions, S‐1‐P lyase null mutants were unable to suppress lateral pseudopod formation like wild‐type control cells. This resulted in a reduction in velocity in buffer and spatial gradients of cAMP. Mutant cells exhibited positive chemotaxis in spatial gradients of cAMP, but did so with lowered efficiency, again because of their inability to suppress lateral pseudopod formation. Mutant cells responded normally to simulated temporal waves of cAMP but mimicked the temporal dynamics of natural chemotactic waves. The effect must be intracellular since no homologs of the S‐1‐P receptors have been identified in the Dictyostelium genome. The defects in the S‐1‐P lyase null mutants were similar to those seen in mutants lacking the genes for myosin IA, myosin IB, and clathrin, indicating that S‐1‐P signaling may play a role in modulating the activity or organization of these cytoskeletal elements in the regulation of lateral pseudopod formation. Cell Motil. Cytoskeleton 59:227–241, 2004. © 2004 Wiley‐Liss, Inc.
Adult glioma incidence trends in the United States, 1977–2000
Authors: Hess Kenneth R. , Broglio Kristine R. , Bondy Melissa L.
Published: October 2004

BACKGROUND

Several authors have reported an increase in the incidence of brain tumors, especially among the elderly. A more complete understanding of adult glioma incidence trends might provide indications of risk factors for gliomas and contribute to the search for improved therapies.

METHODS

The authors used the Surveillance, Epidemiology, and End Results (SEER) registry public use data tapes, which included data on patients with cancer diagnosed between 1973 and 2000. For 3 histologies as well as for 12 histology categories combined, the authors used Poisson regression to model incidence as a function of year of diagnosis, age at diagnosis, race (white or African American), and gender. They used cubic splines to fit age at diagnosis and year of diagnosis and tested for all pair‐wise interactions.

RESULTS

The interaction between year of diagnosis and age at diagnosis was significant in all four groups modeled. In glioblastoma, there was also a significant interaction between gender and age at diagnosis. In anaplastic astrocytoma, there was a significant interaction between gender and year of diagnosis. In oligodendroglioma, there was a significant interaction between race and gender. In the 12 histology categories combined, there was a significant interaction between gender and age at diagnosis.

CONCLUSIONS

The results in the current study were consistent with other published reports that showed an increase in the incidence of brain tumors using SEER data. Although others have observed increasing incidence trends among the elderly, the authors formally tested and found a statistically significant interaction between age at diagnosis and year of diagnosis. Cancer 2004. © 2004 American Cancer Society.
Fibrinogen receptor antagonists induce conformational changes of the human platelet glycoprotein IIb
Authors: Seyfarth Hans‐Juergen , Koksch Mario
Published: October 2004

Background

Controversial results have been reported concerning the ability of fibrinogen receptor antagonists (fibans) to induce conformational changes in the fibrinogen receptor after binding to it as the initial step of fibrinogen binding and platelet activation.

Methods

Platelets in citrated whole blood were stained with several pairs of anti‐glycoprotein (anti‐GP) IIb–directed monoclonal antibodies conjugated to phycoerythrin (PE) or indirectly labeled with Cy5. Pairs of monoclonal antibodies that induced a high‐fluorescence resonance energy transfer (FRET) efficiency served as tools to detect activation‐dependent changes of GP IIb after addition of adenosine diphosphate and several fibans.

Results

Using the combination of the clones 5B12‐PE and P2‐biotin/SA‐Cy5, a concentration‐dependent alteration of the GP IIb conformation was observed after addition of tirofiban, eptifibatide, and lotrafiban. Magnitude and kinetics differed among the investigated substances.

Conclusion

The newly developed FRET assay allows the direct investigation of conformational changes of GP IIb after addition of platelet agonists or receptor ligands, as shown for three fibans. © 2004 Wiley‐Liss, Inc.