bluuebunny/crossref_metadata_2025 huggingface dataset:
Failure Analyses of Polymer Matrix Composite (PMC) Honeycomb Sandwich Joint Panels
Authors: Yeh Hsien-Yang , Nguyen Sean V. , Yeh Hsien-Liang
Published: June 2004

The objective of this paper is to investigate the structural behavior and material failure characteristics of polymer-matrix composite (PMC) honeycomb sandwich joint panels under several transverse loads which resulted in web bending as typically experienced by aircraft wing skin. Several PMC honeycomb sandwich joint panels were fabricated as part of the demonstration test elements to provide structural concepts for the High-Speed Civil Transport (HSCT) wing. Test elements were preliminarily designed and sized under design-integration trade studies (DITS) task. Test elements selected for this study included two PMC honeycomb sandwich joint panels; one panel consisted of a honeycomb sandwich wing skin bolted joint by two fiber-reinforced composite spar caps to a honeycomb sandwich spar web; the other panel had the same structural concept except that the composite spar caps were replaced with the titanium ones. Essential components in the sandwich construction were composite face sheets, honeycomb cores, and core-to-facing bonding material.

By statically loaded test elements to failure in room temperature, the test was designed to simulate flight load condition of 15 psi fuel over pressurization against the wing spar during supersonic maneuver. Geometric linear and nonlinear finite element models were constructed to simulate the structural behaviors of these test panels. Failure theories such as the Yeh-Stratton, Tsai-Wu, Tsai-Hill, and Maximum Stress and Strain criteria were utilized to predict the first ply failure and the results were compared with experimental data.
A Preliminary Multiscale Modeling of Material Failure
Authors: Yeh Hsien-Yang , Yeh Hsien-Liang
Published: June 2004

Microelectromechanical systems (MEMS) and Nanoelectromechanical systems (NAMS) are on the revolutionary frontier of science and engineering. The development of MEMS and NAMS requires appropriate analysis, design, and fabrication techniques that enable the features such as reliability, repeatability, and high yield, etc., in general systems. To achieve this goal, a better understanding of the materials and mechanics at the micro- and nanodimension levels is imperative. In this paper, a preliminary material strength model, for dealing with the resistance to crack propagation at opposite extremes of material representation, continuum solid and atomic lattice, is described.

The development of this model is in two parts:

(1) The crack of continuum solids - using a quadric surfaces function to establish the piecewise failure envelope for incorporating the material anisotropy, and the final failure envelope of the quadric surfaces criterion is closed in order to accommodate the physical justification of materials with finite strengths.

(2) The failure of atomic lattice - representing solids by many-body assemblages of point atomic masses linked by spring bonds, this simplified mass-spring model will be used to express the sequential bond-rupture picture of brittle fracture, in terms of an interatomic cohesive-force function.

In this simplified mass-spring model, the solids are regarded as a simple array of parallel uncoupled linear chains, subject only to longitudinal components of forces, the lattice constraint effects are ignored. By addressing the failure mechanisms and establishing failure theories of not only macroscopic anisotropic composite materials, but also the metal lines at the micro level, results of this preliminary study provide some reference guidelines to do the reliable engineering designs of MEMS and NAMS systems.
Stress Redistribution and Instability in Rotating Orthotropic Cylinders
Authors: Tutuncu Naki , Ozturk Murat
Published: June 2004

The present study addresses the problem of stress redistribution and instability in rotating orthotropic thick-walled cylinders. In the classical approach of determining the stresses and displacements due to a centrifugal force, the inertia force considered does not include the radial displacement. Inclusion of the radial displacement in the centrifugal force results in stress redistribution, and instability occurs at certain rotational speeds. Following a brief outline of the classical analysis, the stress redistribution solutions are presented. The solutions are obtained in terms of non-dimensional parameters. Various cases are considered and the corresponding radial displacement and stress distributions along with their comparisons with the classical results are presented graphically. Critical rotational parameters at the onset of instability are presented in tabular form. It has been shown that increasing the ratio of circumferential stiffness to radial stiffness increases the stability of the cylinder.
Compression Strength of Aqueous Media Exposed Epoxy System Containing Silane Surface Bearing Fly Ash Particles
Authors: Kishore  , Ravikumar N. L. , Kulkarni S. M.
Published: June 2004

Neat epoxy (NE) and epoxy system with different volume fractions of fly ash fillers with their surfaces treated by silane bearing material were made and the responses to exposure by immersion in varying aqueous media, such as plain water (PW), seawater (SW) and seawater containing small amount of dilute hydrochloric acid (SWA) maintained at 80°C, established through weight measurements recorded up to 100 h on the test coupons. Further on, the 100 h exposed samples were subjected to compression tests to evaluate the strength. The results showed that both NE and the silane treated ash bearing composites generally exhibited the highest water absorption in SWA case and the lowest in SW media, with the water absorption level for PW case falling in between. When the ash content in the composite is very large, the water absorption levels tend to be lower for both SW and SWA. The data further showed that unexposed samples recorded less strength compared to the exposed ones. In the case of exposed samples, in all the media employed, as the ash content increases the strength also increases. Further, it was noticed that the samples exposed to SW showed higher strength than the corresponding values noticed with SWA case. Lower strength was found in samples immersed in PW case. Attempts to explain these differing trends are made in this effort by analyzing the features observed on the surface of compression failed samples using fractography technique employing scanning electron microscope (SEM).
Tensile, Impact and Fiber Length Properties of Injection-Molded Short and Long Glass Fiber-Reinforced Polyamide 6,6 Composites
Authors: Hassan A. , Yahya R. , Yahaya A. H. , Tahir A. R. M. , Hornsby P. R.
Published: June 2004

Injection molding of fiber-reinforced polymer composites is associated with the problem of fiber breakage. If the fiber length retained in the finish product is too short, it will limit the expected improvement in the property. Extrusion and pultrusion are two methods normally employed for the melt compounding of polymer composite feedstock for the injection molding and produced short- and long-fiber composites (SFCs and LFCs), respectively. In this work, short- and long-glass fiber-reinforced polyamide 6,6 composites were injection molded at different fiber loading and tested for the tensile properties, impact properties and fiber length characteristics. It was found that both tensile strength and tensile modulus of LFCs improved compared to the SFCs counterpart despite reduction in fracture strain, while pultrusion compounded composites also showed superior fiber characteristics, in terms of fiber length distribution, Ln, Lw, etc. compared to the extrusion compounded composites counterpart. Fiber length characteristics were also in agreement with the improvement in tensile strength and tensile modulus of LFCs over the SFCs. Impact properties of LFCs also show some improvement compared to the SFCs counterpart with equivalent composition, despite longer fiber retained in composites.
To Have or to Take: Discourse, Positioning, and Narrative Identity in Women’s Accounts of HRT
Authors: Stephens Christine , Carryer Jenny , Budge Claire
Published: June 2004

Using ‘social cognitive’ frameworks, attitudes to HRT have been examined as if they were stable entities located within individuals. However, qualitative studies have revealed variations and contradictions in women’s ‘attitudes’. We seek to explain these apparent contradictions by using a social constructionist approach to the analysis of qualitative data from 7 focus group discussions about HRT with 48 women in New Zealand. A discourse analysis of ‘interpretative repertoires’, subject positions and narrative identity was undertaken to explain the construction of HRT in situated practice, and the negotiation and accomplishment of a unitary orientation to HRT across situations. The results summarize the interpretative repertoires used by the women, and one example of a subject position negotiated at a moment of patently problematic intersecting interpretative repertoires, to highlight the construction of subject positions using discursive resources. The importance of the study of subjectivity in applied areas of psychology is discussed.
Blundering toward critical pedagogy: True tales from the adult literacy classroom
Authors: Belzer Alisa
Published: May 2004

Critical practice in adult literacy education offers many interesting and important challenges, including creating a situation in which learners and instructors can communicate across their differences.
Consumerism, consumption, and a critical consumer education for adults
Authors: Sandlin Jennifer A.
Published: May 2004

This chapter explores the connection between consumerism, consumption, and adult education, arguing for a more critical form of consumer education for adults.
Teaching with the enemy: Critical adult education in the academy
Authors: St.Clair Ralf
Published: May 2004

The author identifies issues facing critical adult educators in academic settings and argues for instructors' and students' active engagement with critique.
Toward a postmodern pedagogy
Authors: Kilgore Deborah
Published: May 2004

What does teaching from a postmodern perspective mean? This chapter describes adult education from one educator's standpoint, with attention to knowledge, teachers, students, and power.
Africentric philosophy: A remedy for eurocentric dominance
Authors: Hunn Lisa Merriweather
Published: May 2004

This chapter juxtaposes Africentrism and Eurocentrism, leading to suggestions for creating a practice that avoids the reproduction of oppression arising from adult education's overreliance on a Eurocentric worldview.
Activism as practice: Some queer considerations
Authors: Hill Robert J.
Published: May 2004

This chapter explores how theory, activism, and practice around sexual orientation and gender identity come together, as viewed through the lens of queer critical postmodernism.
Using critical personal narratives: A poststructural perspective on practice
Authors: Chapman Valerie‐Lee
Published: May 2004

The stories we tell about ourselves and our teaching reveal how language, power, knowledge, and customary instructional practices work together to construct appropriate identities and behaviors in both learners and teachers.
Why liquid displacement methods are sometimes wrong in estimating the pore‐size distribution
Authors: Gijsbertsen‐Abrahamse Anna J. , Boom Remko M. , van der Padt Albert
Published: June 2004

The liquid displacement method is a commonly used method to determine the pore size distribution of micro‐ and ultrafiltration membranes. One of the assumptions for the calculation of the pore sizes is that the pores are parallel and thus are not interconnected. To show that the estimated pore size distribution is affected if this assumption is not satisfied, we developed two models: (1) a model describing the flow through an isotropic porous membrane with uniform pores, and (2) a two‐layer model for uniform pores that approximates the first model if the membrane thickness is larger than 10 times the pore radius. In the two‐layer model the membrane skin layer is divided into two parts: the unconnected pore layer and a sublayer. This model is extended to describe pore activation as a function of pressure with a pore size distribution in the unconnected pore layer (that is, membrane surface). It is shown that, depending on the membrane thickness or the sublayer resistance, the transmembrane pressure needs to be much larger than the critical pressure of the pores, to activate all the pores. If the sublayer resistance is over 10% of the resistance of the unconnected pore layer, the pore size is underestimated with the liquid displacement method; thus the number of pores is overestimated. Because the sublayer resistance is always larger than the unconnected pore layer resistance in an isotropic membrane with interconnected pores, we conclude that the estimated pore size distribution is always shifted toward smaller pore sizes than they really are. To use the liquid displacement method correctly, we suggest either counting the number of (active) pores or measuring the flux–pressure curve several times, while covering each time a different fraction of the membrane surface. © 2004 American Institute of Chemical Engineers AIChE J, 50: 1364–1371, 2004
Dynamical systems in pin mixers of single‐screw extruders
Authors: Hwang W. R. , Kang K. W. , Kwon T. H.
Published: June 2004

Dynamical systems generated by various types of pin mixers were studied for the application to the single‐screw extruders. A periodic unit of the pin mixer was modeled as a dynamical system of the complex duct flow. It was found that the cross‐sectional space could be divided into two distinct regions: the inner and outer zones. The pin configuration directly affects the motion of fluid particles in the inner region, while motion in the outer region is governed by the resonance phenomena. The effects of the number of pins, the pin height, the pin orientation, and the composition of two different pin units were studied with the numerical results and explained in the language of the dynamical systems theories. Finally, the validity of our modeling, and the numerical result was verified by qualitative comparison with experimental results. © 2004 American Institute of Chemical Engineers AIChE J, 50: 1372–1385, 2004
Association study of the Epac gene and tobacco smoking and nicotine dependence
Authors: Chen Xiangning , Wu Baichai , Kendler Kenneth S.
Published: May 2004

Exchange protein directly activated by cAMP (Epac) has been shown to increase its expression in rat prefrontal cortex after self‐administration of nicotine. [Konu et al. 2001: Brain Res 909:194–203]. We investigated the role of the human ortholog of Epac in tobacco smoking and nicotine dependence (ND). Using a case‐control design, we typed 5 SNPs in this gene in 688 subjects, of whom 244 were non‐smokers, 215 were Low‐ND smokers, and 229 were High‐ND smokers. We tested allele and genotype association to smoking initiation (SI) and progression to ND. Three of the five typed SNPs showed modest allele association with progression to ND. Weak association with SI was also observed for one SNP. Considering the function of the gene in cellular signal transduction pathway, its elevated expression after nicotine self‐administration, and multiple markers association with both SI and progression to ND, it is plausible to suggest that variants in Epac contribute to the liability to ND. © 2004 Wiley‐Liss, Inc.
Apoptosis and testicular alterations in albino rats treated with etoposide during the prepubertal phase
Authors: Stumpp Taiza , Sasso‐Cerri Estela , Freymüller Edna , Miraglia Sandra Maria
Published: June 2004

Etoposide is a podophyllotoxin semiderivative that is used in a variety of chemotherapy treatments, including therapy for children tumors. This drug promotes the formation of a ternary DNA‐topoisomerase II‐etoposide complex that triggers apoptosis. The purpose of this work was to analyze the occurrence of apoptosis in the seminiferous epithelium of prepubertal, pubertal, and adult rats treated with 10, 20, and 40 mg/Kg of etoposide during the prepubertal phase, as well as the role of apoptosis in etoposide‐induced testicular damage. The rat testes were fixed in Bouin's liquid, and the apoptotic cells were quantified by means of the hematoxylin and eosin (H&E) technique (all groups) and the terminal dUTP nick end labeling (TUNEL) method (prepubertal groups only). The results obtained from both the H&E and TUNEL methods showed an increased frequency of apoptosis in the seminiferous epithelium of treated animals, except for the subgroup that received the 10‐mg/Kg dose and was sacrificed 12 hr after the treatment and for the etoposide‐treated pubertal group, that did not show cells suggesting apoptosis during H&E analysis. The labeled cells were mainly primary spermatocytes and differentiated spermatogonia. The prepubertal rats showed an etoposide‐dose‐dependent diminution of differentiated spermatogonia. Etoposide treatment during the prepubertal phase increases the frequency of apoptosis in the seminiferous epithelium, and causes serious harm to male fertility. 2004. © 2004 Wiley‐Liss, Inc.
Neuroanatomical structure of the spinner dolphin (Stenella longirostris orientalis) brain from magnetic resonance images
Authors: Marino Lori , Sudheimer Keith , Mclellan William A. , Johnson John I.
Published: June 2004

High‐resolution magnetic resonance (MR) images of the brain of an adult spinner dolphin (Stenella longirostris orientalis) were acquired in the coronal plane at 55 antero‐posterior levels. From these scans a computer‐generated set of resectioned virtual images in the two remaining orthogonal planes was constructed with the use of the VoxelView and VoxelMath (Vital Images, Inc.) programs. Neuroanatomical structures were labeled in all three planes, providing the first labeled anatomical description of the spinner dolphin brain. © 2004 Wiley‐Liss, Inc.
Role of interleukin‐18 in experimental group B streptococcal arthritis
Authors: Tissi Luciana , McRae Bradford , Ghayur Tariq , von Hunolstein Christina , Orefici Graziella , Bistoni Francesco , Puliti Manuela
Published: June 2004

Objective

To assess the role of interleukin‐18 (IL‐18) in the evolution of septic arthritis induced by group B streptococci (GBS) in mice.

Methods

CD1 mice were inoculated intravenously with 8 × 106 colony‐forming units (CFU) of type IV GBS (strain 1/82), and administered intraperitoneally 1 hour before infection with anti–IL‐18 monoclonal antibodies (0.25 mg/mouse). In a subsequent set of experiments, mice infected with a suboptimal arthritogenic dose of GBS (4 × 106 CFU/mouse) were administered different doses of recombinant IL‐18 for 4 days, starting 1 hour after infection. Mortality, evolution of arthritis, bacterial clearance, joint histopathology, and cytokine production were examined in infected mice that did or did not receive treatment with anti–IL‐18 antibodies or IL‐18.

Results

IL‐18 was produced during GBS infection. Neutralization of IL‐18 resulted in a decrease in mortality rates, and in the incidence and severity of arthritis. Amelioration of arthritis was accompanied by a dramatic reduction in local IL‐1β, IL‐6, macrophage inflammatory protein 1α (MIP‐1α) and MIP‐2 production, and reduced bacterial burden. Administration of exogenous IL‐18 resulted in increased mortality rates and increased incidence and severity of GBS arthritis, concomitant with a higher number of GBS and increased levels of IL‐6, IL‐1β, MIP‐1β, and MIP‐2 production in the joints.

Conclusion

The present study indicated some involvement of IL‐18 in the pathogenesis of GBS‐induced arthritis. The role of IL‐18 in joint pathology is shown by a regulatory effect on inflammatory mediator levels and local cell influx. Thus, IL‐18 should be regarded as a potential therapeutic target in GBS infection and arthritis.
Increased synovial tissue NF‐κB1 expression at sites adjacent to the cartilage–pannus junction in rheumatoid arthritis
Authors: Benito Maria J. , Murphy Eithne , Murphy Evelyn P. , van den Berg Wim B. , FitzGerald Oliver , Bresnihan Barry
Published: June 2004

Objective

To compare the expression of the Rel/NF‐κB subunits, NF‐κB1 (p50) and RelA (p65), in paired synovial tissue samples selected from sites adjacent to and remote from the cartilage–pannus junction (CPJ) in patients with inflammatory arthritis.

Methods

Synovial tissue was selected at arthroscopy from sites adjacent to the CPJ and from the suprapatellar pouch of patients who were referred to an early arthritis clinic. Tissue samples from patients with osteoarthritis (OA) undergoing knee arthroplasty were also studied. Rel/NF‐κB subunit activation and expression were measured by electrophoretic mobility shift assay and supershift analyses and by immunohistochemistry.

Results

Tissue samples were obtained from 10 patients with rheumatoid arthritis (RA), 7 with a seronegative arthropathy (SnA), and 6 with OA. Rel/NF‐κB was abundantly expressed in all samples. In both RA and SnA synovial tissue, the absolute number of NF‐κB1+ cells at the CPJ was significantly higher than at non‐CPJ sites (P = 0.006 and P = 0.02, respectively). The proportion of cells expressing NF‐κB1 was also significantly higher at the CPJ compared with non‐CPJ sites (P = 0.003 in RA, P = 0.009 in SnA). The numbers of RelA+ cells were consistently lower throughout. In RA synovial tissue, but not in SnA synovial tissue, both the absolute number and the proportion of RelA+ cells were significantly higher at the CPJ than at non‐CPJ sites (P = 0.003 and P = 0.01, respectively). In OA synovial tissue, the numbers of cells expressing NF‐κB1 and RelA were similar to those observed at the non‐CPJ sites in all inflammatory tissues studied.

Conclusion

In this study of early inflammatory arthritis, expression of NF‐κB1 in synovial tissue was highest at sites most likely to be associated with joint erosion. These observations are consistent with a critical role of NF‐κB1 in joint destruction, and support the rationale for specific therapeutic inhibition of NF‐κB in RA.
Chromatin breakdown during necrosis by serum Dnase1 and the plasminogen system
Authors: Napirei Markus , Wulf Swantje , Mannherz Hans Georg
Published: June 2004

Objective

Dnase1‐deficient mice with the 129 × C57BL/6 genetic background develop symptoms of systemic lupus erythematosus, such as high titers of antinuclear autoantibodies directed against nucleosomes. In this study we analyzed a potential molecular pathomechanism leading to this autoimmunity, by exploring the influence of extracellular Dnase1 present in serum on the breakdown of chromatin in necrotic cells in vitro.

Methods

Human breast adenocarcinoma cells (MCF‐7) and other cell lines were subjected to necrosis induced by hydrogen peroxide, streptolysin O, or freeze‐thawing. Subsequently, the influence of sera from Dnase1‐deficient and wild‐type mice as well as the influence of purified enzymes present in the culture medium on the process of necrotic chromatin breakdown was investigated.

Results

Necrotic chromatin breakdown resembled apoptotic DNA laddering and was catalyzed by serum Dnase1 in conjunction with plasmin. During necrosis, Dnase1 and plasminogen penetrated the cell and accumulated in the cytoplasm and nucleus. Plasminogen bound to the cytoskeleton and nuclear structures, was activated to plasmin by either tissue‐type or urokinase‐type plasminogen activator, and degraded histone H1, thereby facilitating internucleosomal DNA cleavage by Dnase1.

Conclusion

Our results suggest that serum Dnase1 in cooperation with the plasminogen system guarantees a fast and effective breakdown of chromatin during necrosis by the combined cleavage of DNA as well as of DNA binding proteins. The failure of such a clearance mechanism might lead to antinuclear autoimmunity similar to that observed in the Dnase1‐deficient mouse.
Altered blood B lymphocyte homeostasis in systemic sclerosis: Expanded naive B cells and diminished but activated memory B cells
Authors: Sato Shinichi , Fujimoto Manabu , Hasegawa Minoru , Takehara Kazukiko
Published: June 2004

Objective

To determine phenotypic and functional abnormalities of blood B cell subsets in patients with systemic sclerosis (SSc).

Methods

Cell surface marker expression was determined by flow cytometry. Spontaneous apoptosis was evaluated by annexin V expression with flow cytometric analysis. IgG production by isolated IgD− memory B cells was examined by enzyme‐linked immunosorbent assay.

Results

The numbers of blood CD27− naive B cells from SSc patients were increased compared with normal control cells, while memory B cells expressing medium levels of CD27 and plasmablasts expressing high levels of CD27 were reduced. In contrast, plasmablasts were the predominant population in patients with systemic lupus erythematosus (SLE). Memory B cells in SSc showed increased expression of activation markers, including CD80, CD86, and CD95, relative to normal controls. Consistent with CD95 up‐regulation, SSc memory B cells exhibited augmented spontaneous apoptosis after 24‐hour incubation; augmented apoptosis may explain the reduced memory B cell number. Nonetheless, isolated IgD− SSc memory B cells treated with stimuli had an enhanced ability to produce IgG. Furthermore, expression of CD19, a critical signal transduction molecule of B cells that regulates autoantibody production, was significantly increased in memory B cells as well as in naive B cells in SSc. In contrast, CD19 expression was decreased in SLE B cells.

Conclusion

SSc patients have distinct abnormalities of blood homeostasis and B cell compartments, characterized by expanded naive B cells and activated but diminished memory B cells. Our results suggest that CD19 overexpression in SSc memory B cells is related to their hyperreactivity.
Up‐regulated expression and activation of the orphan chemokine receptor, CCRL2, in rheumatoid arthritis
Authors: Galligan Carole L. , Matsuyama Wataru , Matsukawa Akihiro , Mizuta Hiroshi , Hodge David R. , Howard O. M. Zack , Yoshimura Teizo
Published: June 2004

Objective

Rheumatoid arthritis (RA) is a chronic inflammatory condition characterized by a cellular influx and destruction of the joint architecture. Chemokines characteristically regulate leukocyte recruitment and activation. Chemokine (CC motif) receptor–like 2 (CCRL2) is an orphan receptor with homology to other CC chemokine receptors. We undertook this study to examine CCRL2 expression in RA, cytokine regulation of expression, and the source of a putative ligand in an attempt to determine the role of this receptor during inflammation.

Methods

Expression of CCRL2 on joint‐infiltrating leukocytes was examined by immunocytochemistry. In vitro studies evaluated CCRL2 expression in primary neutrophils using Northern and Western blotting and reverse transcriptase–polymerase chain reaction. HEK 293 cells expressing two splice variants of CCRL2 (HEK/CCRL2A or HEK/CCRL2B) were generated with a retroviral expression system, and their migration in response to fractions of synovial fluid (SF) from RA patients was examined using a 48‐well chamber.

Results

CCRL2 expression was observed on all infiltrating neutrophils and on some macrophages obtained from the SF of 5 RA patients. In vitro studies of primary neutrophils revealed that CCRL2 messenger RNA (mRNA) was rapidly up‐regulated following stimulation with lipopolysaccharide (1 μg/ml) or tumor necrosis factor (5 ng/ml). The mRNA for both CCRL2A and CCRL2B were expressed in cytokine‐stimulated neutrophils. Cells expressing either of these splice variants migrated in response to a fraction of RA SF.

Conclusion

CCRL2 expression is up‐regulated on synovial neutrophils of RA patients. Inflammatory products present in the SF activate this receptor, indicating that CCRL2 is a functional receptor that may be involved in the pathogenesis of RA.
Abnormalities in peripheral B cell memory of patients with primary Sjögren's syndrome
Authors: Hansen Arne , Gosemann Mirko , Pruss Axel , Reiter Karin , Ruzickova Sarka , Lipsky Peter E. , Dörner Thomas
Published: June 2004

Objective

To delineate disturbances in peripheral B cell memory in primary Sjögren's syndrome (SS).

Methods

Isotype‐specific immunoglobulin (Ig) heavy‐chain transcripts were analyzed in single‐sorted CD19+,CD27− naive and CD19+,CD27+ memory B cells from patients with primary SS and normal healthy control subjects.

Results

A significantly higher frequency of B cells expressing μ‐, α‐, and/or γ‐chain transcripts were found in patients with primary SS compared with controls (58.0% versus 14.3%; P < 0.0001). Notably, 30.5% of individual B cells (for primary SS, 38.7%; for controls, 12.7% [P < 0.0001]) simultaneously expressed transcripts for different Ig heavy‐chain isotypes using identical VH–D–JH rearrangements. However, these cells lacked surface expression of more than one of the respective Ig heavy‐chain isotypes as well as messenger RNA (mRNA) transcripts for 2 germinal center markers, activation‐induced cytidine deaminase, and Bcl‐6. In contrast with the findings in normal healthy controls, peripheral B cell memory in patients with primary SS was characterized by 1) circulating CD27+ B cells expressing heavily mutated Ig VH transcripts (mutational frequency 8.6% versus 4.3%; P < 0.0001), 2) significantly enhanced mutational frequencies of Cμ transcripts (9.6% versus 2.5%; P < 0.0001), 3) a high proportion (61.2%) of CD27+ B cells expressing transcripts for multiple Ig heavy‐chain isotypes, and 4) a CD27− memory‐type B cell subpopulation expressing mutated Cμ transcripts.

Conclusion

Altogether, both B cell hyperactivity and striking abnormalities in peripheral B cell memory are indicated at the single‐cell mRNA level in patients with primary SS. Detection of multiple Ig heavy‐chain transcripts in peripheral CD19+,CD27+ memory B cells of patients with SS may represent the abnormal retention of pre‐switch mRNA transcripts in circulating post‐switch B cells.
The safety of anakinra in high‐risk patients with active rheumatoid arthritis: Six‐month observations of patients with comorbid conditions
Authors: Schiff Michael H. , DiVittorio Gino , Tesser John , Fleischmann Roy , Schechtman Joy , Hartman Sanford , Liu Thomas , Solinger Alan M.
Published: June 2004

Objective

To determine in a placebo‐controlled, double‐blind trial the safety profile of daily anakinra (Kineret) use in patients with active rheumatoid arthritis (RA) and concurrent comorbid conditions.

Methods

In 169 centers in 9 countries, 1,414 patients with active RA were randomly assigned to receive either anakinra (100 mg) or placebo treatment (4:1 anakinra‐to‐placebo allocation ratio), with study drug administered by daily subcutaneous injection for 6 months. The current post hoc analysis assessed baseline comorbid conditions, and patients were considered at high risk for the occurrence of adverse events if they had a history of at least one of the following: cardiovascular event, pulmonary event, central nervous system–related event, infection, diabetes, malignancy, or renal impairment. Within each treatment group (anakinra or placebo), incidence rates were summarized for serious adverse events, infectious events, and serious infectious events in high‐risk patients and compared with these incidence rates in patients without comorbid conditions.

Results

The majority of patients in the trial had one or more comorbid conditions. In these high‐risk patients, there were no differences in the incidence of serious adverse events or infectious events between treatment groups. The incidence of serious infectious events with anakinra use was similar between high‐risk patients (2.5%) and the entire study population (2.1%) and was not attributable to any single comorbidity.

Conclusion

Results of the analysis of adverse events in patients with active RA and coexisting comorbidities suggest that the favorable safety profile of anakinra is maintained in a high‐risk patient population.
Association of the PD‐1.3A allele of the PDCD1 gene in patients with rheumatoid arthritis negative for rheumatoid factor and the shared epitope
Authors: Prokunina Ludmila , Padyukov Leonid , Bennet Anna , de Faire Ulf , Wiman Björn , Prince Jonathan , Alfredsson Lars , Klareskog Lars , Alarcón‐Riquelme Marta
Published: June 2004

Objective

To study the frequency of allele A of polymorphism PD‐1.3 of the PDCD1 gene in patients with rheumatoid arthritis (RA) and its subsets, based on the presence of rheumatoid factor (RF) and the shared epitope (SE) alleles.

Methods

A total of 1,175 patients with RA and 3,404 controls were genotyped for the PD‐1.3 A/G polymorphism, which previously was identified as being involved in susceptibility to systemic lupus erythematosus (SLE) in patients of European descent.

Results

We first detected a trend for association of allele A of the single‐nucleotide polymorphism PD‐1.3 with RA (P = 0.053, odds ratio [OR] 1.18, 95% confidence interval [95% CI] 0.99–1.41). To further clarify the nature of this association, patients with RA were divided into 4 groups according to the presence of RF and the SE alleles. Association was found only in the group of patients negative for both RF and the SE alleles (P = 0.0054 [corrected P = 0.015], OR 1.75, 95% CI 1.15–2.65).

Conclusion

Patients negative for both RF and the SE alleles showed association with the same allele that we previously identified as being involved in susceptibility to SLE. These results provide the first evidence of the involvement of the human PDCD1 gene in arthritis.
Induction of arthritis in HLA–DR4–humanized and HLA–DQ8–humanized mice by human cartilage proteoglycan aggrecan but only in the presence of an appropriate (non‐MHC) genetic background
Authors: Szántó Sándor , Bárdos Tamás , Szabó Zoltán , David Chella S. , Buzás Edit I. , Mikecz Katalin , Glant Tibor T.
Published: June 2004

Objective

To determine whether the rheumatoid arthritis (RA)–predisposing class II molecules of the major histocompatibility complex (MHC) can present cartilage proteoglycan (PG) aggrecan, and if so, to determine the epitope repertoire of the human cartilage PG in HLA‐transgenic mice and determine whether HLA‐transgenic mice develop arthritis in response to immunization with human cartilage PG.

Methods

Mice transgenic for HLA–DR2.Ab0, DR3.Ab0, DR4.Ab0, and DQ8.Ab0, lacking their own (mouse) class II antigens (Ab0), on the original (arthritis‐resistant) and the arthritis‐susceptible BALB/c backgrounds, were immunized with human cartilage PG. The T cell epitope repertoire presented by these class II MHC alleles was determined using a synthetic peptide library (143 peptides of the core protein of human cartilage PG), and arthritis development was monitored and compared in wild‐type and HLA‐transgenic/congenic BALB/c mice.

Results

Mice of the 4 HLA‐transgenic lines, either on the original mixed, arthritis‐resistant background or DR4.Ab0‐ and DQ8.Ab0‐transgenic/congenic mice on the arthritis‐susceptible BALB/c genetic background, responded well to PG immunization (as assessed by T cell responses and antibody and cytokine production), and a number of T cell epitopes along the core protein of human cartilage PG were identified. DR4.Ab0‐ and DQ8.Ab0‐transgenic mice immunized with human cartilage PG developed arthritis, but only when these class II MHC molecules were present on the arthritis‐susceptible (BALB/c) genetic background.

Conclusion

A number of human cartilage PG epitopes can be presented by HLA alleles that predispose to the development of RA, but the epitopes of the cartilage PG presented by HLA–DR4 or HLA–DQ8 can induce arthritis only in the presence of an appropriate genetic (non‐MHC) background.
Expression of microsomal prostaglandin E synthase 1 in rheumatoid arthritis synovium
Authors: Westman M. , Korotkova M. , Klint E. af , Stark A. , Audoly L. P. , Klareskog L. , Ulfgren A.‐K. , Jakobsson P.‐J.
Published: June 2004

Objective

Microsomal prostaglandin E synthase 1 (mPGES‐1) catalyzes the formation of PGE2 from cyclooxygenase‐derived PGH2. Microsomal PGES‐1 is induced by proinflammatory cytokines and is strongly linked to conditions that result in high PGE2 biosynthesis. PGE2 contributes to the pathogenesis of rheumatoid arthritis (RA), acting as a mediator of inflammation and promoting bone destruction. Induction of mPGES‐1 in rheumatoid synoviocytes by proinflammatory cytokines has been demonstrated in vitro, indicating an important role in RA pathogenesis. Recent studies using mPGES‐1–deficient mice demonstrated the importance of this gene in chronic inflammation. The aim of this study was to investigate the expression and localization of mPGES‐1 in synovial biopsy specimens obtained from patients with RA.

Methods

Synovial tissue samples from 24 patients with RA were obtained, and immunohistologic analysis was performed using polyclonal antibodies against mPGES‐1. Double immunofluorescence staining was performed with antibodies to CD3, CD19, CD20, CD68, CD163, and prolyl 4‐hydroxylase.

Results

Intracellular mPGES‐1 staining was observed in synovial membranes from all of the RA patients studied. Specifically, strong expression of mPGES‐1 was detected in synovial lining cells. In sublining mononuclear and fibroblast‐like cells, the extent of mPGES‐1 staining was less than that in the synovial lining cells. In some patients, positive staining was observed in endothelial cells. With the double immunofluorescence technique, mPGES‐1 production was detected in synovial macrophages and fibroblasts, while mPGES‐1 expression was not observed in lymphocytes.

Conclusion

The demonstration of mPGES‐1 expression in synovial tissues from patients with RA suggests a role for mPGES‐1 in the RA disease process. Microsomal PGES‐1 might be a potential new target for treatment strategies to control PGE2 synthesis in patients with RA, without the systemic side effects associated with cyclooxygenase inhibitors.
Control of spontaneous B lymphocyte autoimmunity with adenovirus‐encoded soluble TACI
Authors: Liu Weimin , Szalai Alex , Zhao Limin , Liu Di , Martin Flavius , Kimberly Robert P. , Zhou Tong , Carter Robert H.
Published: June 2004

Objective

Serum B lymphocyte stimulator (BLyS) is increased in autoimmune diseases, both in animal models and in humans. This study examined the effect of BLyS blockade in 3 animal models of lupus.

Methods

Antibodies and lupus‐like disease manifestations were examined in mice after administration of a single injection of an adenoviral construct for the transmembrane activator and CAML interactor receptor (AdTACI) that produces high serum levels of TACI‐Fc fusion protein.

Results

In C57BL/6 (B6) lpr/lpr mice (B6.lpr/lpr), which were used to model autoimmunity in the absence of severe disease, treatment of younger mice with AdTACI prevented the development of hypergammaglobulinemia. In contrast, use of AdTACI for BLyS blockade had only transient effects on the levels of IgG in normal B6 mice. AdTACI blocked the development of autoantibodies in younger B6.lpr/lpr mice and reversed the production of autoantibodies in older B6.lpr/lpr mice, and also reduced the numbers of splenic plasma cells. In MRL.lpr/lpr mice, which were used to examine disease manifestations, AdTACI reduced the extent of glomerulonephritis and proteinuria and improved survival, but had little effect on T cell infiltration and interstitial nephritis. However, in (NZB × NZW)F1 mice, AdTACI induced neutralizing anti‐TACI antibodies and failed to reduce the numbers of B cells.

Conclusion

BLyS blockade has little effect on IgG levels in normal mice, but reverses the production of spontaneously produced IgM and IgG autoantibodies in the setting of established autoimmunity. Blockade of BLyS ameliorates B cell–dependent disease manifestations even in the MRL.lpr/lpr model, but its effectiveness on autonomous T cell aspects of the disease is limited. Moreover, its effectiveness is neutralized by anti‐TACI antibodies when present. These results provide a basis for understanding the potential effects of BLyS blockade in human disease.
Health‐related quality of life in systemic sclerosis as measured by the short form 36: Relationship with clinical and biologic markers
Authors: Del Rosso Angela , Boldrini Maura , D'Agostino David , Placidi Giovanni Plinio Augusto , Scarpato Alessandra , Pignone Alberto , Generini Sergio , Konttinen Yrio , Zoppi Massimo , Vlak Tonko , Placidi Gianfranco , Matucci‐Cerinic Marco
Published: June 2004

Objective

To evaluate health‐related quality of life (HRQOL) in patients with systemic sclerosis (SSc) using the Short Form 36 (SF‐36) and to correlate SF‐36 scores with clinical and biologic markers.

Methods

The SF‐36 was administered to 24 controls and 24 SSc patients. SSc patients also were evaluated for subset (limited SSc [lSSc] and diffuse SSc [dSSc]), age, disease duration, angiotensin‐converting enzyme (ACE) levels, autoantibodies, and skin and internal organ involvement.

Results

The physical summary score (PSS) was lower in SSc patients than in controls (P < 0.05), whereas the mental summary score (MSS) was higher in dSSc than in lSSc patients (P < 0.05). Five of 8 single SF‐36 domain scores were lower in SSc patients than in controls (P < 0.05). Vitality was higher in dSSc than in controls (P < 0.001). In SSc, elder age correlated with lower PSS; low ACE levels and high skin score correlated with higher general mental health and role limitations due to physical problems, respectively (P < 0.05). Patients with heart involvement had higher scores in general health perceptions (P < 0.05).

Conclusion

The SF‐36 shows that HRQOL is impaired in patients with SSc. Higher scores in MSS and vitality in patients with dSSc and correlations of high SF‐36 scores with specific organ involvement suggest that SSc patients with severe disease are more able to cope with HRQOL modification.
Health‐related quality of life and health service use among older adults with osteoarthritis
Authors: Dominick Kelli L. , Ahern Frank M. , Gold Carol H. , Heller Debra A.
Published: June 2004

Objective

To examine the relationship between health‐related quality of life (HRQOL) and health service use among older adults with osteoarthritis (OA).

Methods

Subjects were 9,043 Medicare‐enrolled survey respondents with a prior International Classification of Diseases, Ninth Revision code for OA. Analyses examined the relationship of 5 Centers for Disease Control and Prevention HRQOL items (general health, mental health, pain, activity limitation, and sleep) to physician visits, prescription analgesic or antiinflammatory use, and arthroplasty during 1 year of followup.

Results

In analyses controlling for demographic and health‐related variables, greater pain frequency was associated with increased odds of visiting a physician, using analgesic or antiinflammatory drugs, and having arthroplasty (P < 0.001). Poorer general health was associated with increased odds of analgesic or antiinflammatory use but decreased odds of arthroplasty (P < 0.01). More days of activity limitation and poor mental health were associated with decreased odds of analgesic or antiinflammatory use (P < 0.01).

Conclusion

These HRQOL variables, especially pain frequency, can be valuable tools for estimating future health care use among older adults with OA.
Assessment of atherosclerotic risk factors and endothelial function in children and young adults with pediatric‐onset systemic lupus erythematosus
Authors: Soep Jennifer B. , Mietus‐Snyder Michele , Malloy Mary J. , Witztum Joseph L. , Von Scheven Emily
Published: June 2004

Objective

To characterize atherosclerotic risk factors and endothelial function in pediatric‐onset systemic lupus erythematosus (SLE).

Methods

Lipoproteins, oxidized state, and autoantibodies to oxidized low‐density lipoprotein (Ox‐LDL) were assessed. Endothelial function was evaluated using brachial artery reactivity.

Results

Thirty‐three SLE patients and 30 controls were studied. SLE subjects had significantly decreased mean high‐density lipoprotein (HDL) cholesterol (41 mg/dl versus 51 mg/dl; P = 0.002) and apolipoprotein A‐I (97 mg/dl versus 199 mg/dl; P = 0.0004). There was no difference between groups in markers of oxidized state (including nitric oxide metabolites, isoprostanes, and Ox‐LDL) or in endothelial function. However, SLE subjects had increased median anti‐Ox‐LDL IgG (2,480 relative light units [RLU] versus 1,567 RLU; P = 0.0007) and IgG immune complexes with LDL (4,222 RLU versus 2,868 RLU; P = 0.002).

Conclusion

Pediatric SLE patients had significantly decreased levels of HDL cholesterol and apolipoprotein A‐I and elevated titers of autoantibodies to Ox‐LDL. Despite these atherosclerotic risk factors, SLE patients had normal measures of oxidized state and endothelial function.
Spanish Arthritis Empowerment Program: A dissemination and effectiveness study
Authors: Wong Andrew L. , Harker Judith O. , Lau Victoria P. , Shatzel Sue , Port Lori H.
Published: June 2004

Objective

To evaluate the effectiveness of the Spanish Arthritis Empowerment Program as presented by the Arthritis Foundation, Southern California Chapter, in Orange County, California.

Methods

Participants with arthritis (n = 141) enrolled in the program between October 1999 and May 2001. All materials were in Spanish. Written pretest, 6‐week posttest, and 6‐month followup tests measured pain rating, self‐report joint counts, function (modified Health Assessment Questionnaire [mHAQ]), self efficacy, self‐care behavior, and arthritis knowledge.

Results

Mean age was 51 years, 92% were female, 84% were born in Mexico, 55% had sixth grade education or less, and 60% had no medical insurance. Of the 141 participants, 118 completed 6‐month followup testing. Repeated‐measures analysis of variance showed significant improvement from pretest to 6‐month followup in pain (6.0 versus 3.4); self efficacy (5.5 versus 8.4), self‐care behavior (1.7 versus 4.9), arthritis knowledge (1.6 versus 4.5), and general health (2.1 versus 2.5), all at P < 0.001. Small improvement was reported in mHAQ (0.56 versus 0.50; P = 0.024).

Conclusion

The Spanish Arthritis Empowerment Program was successfully disseminated. Significant improvements in self efficacy and in arthritis symptoms were maintained at the 6‐month followup.
Gap between short‐ and long‐term effects of patient education in rheumatoid arthritis patients: A systematic review
Authors: Niedermann Karin , Fransen Jaap , Knols Ruud , Uebelhart Daniel
Published: June 2004

Objective

To systematically review educational or psychoeducational interventions for patients with rheumatoid arthritis focusing on long‐term effects, especially health status.

Methods

Two independent reviewers appraised the methodologic quality of the included randomized controlled trials, published between 1980 and July 2002.

Results

Validity scores of studies ranged from 3 to 9 (of 11). The 7 educational programs mainly improved knowledge and compliance in the short and long term, but there was no improvement in health status. All 4 psychoeducational programs improved coping behavior in the short term, 2 of them showing a positive long‐term effect on physical or psychological health variables.

Conclusion

Methodologically better‐designed studies had more difficulties demonstrating positive outcome results. Short‐term effects in program targets are generally observed, whereas long‐term changes in health status are not convincingly demonstrated. There is a need to find better strategies to enhance the transfer of short‐term effects into gains in health status.