bluuebunny/crossref_metadata_2025 huggingface dataset:
THE CONTINUING SIGNIFICANCE OF CLASS: CONFRONTING CAPITALISM IN AN ANARCHIST COMMUNITY
Authors: Robinson Christine M.
Published: September 2009

As the national preoccupation with terrorism gives way to an unfolding, and likely enduring, economic crisis in the U.S. and globally, social research should focus more attention toward class‐based social movements, which have largely been neglected within sociology and social movement scholarship over the last few decades. Class analysis and labor organizing have historically been central to the social movement activities of anarchists. Anarchist social movements are relatively understudied, despite indicators of their resurgence in the last decade. Today, however, anarchist politics have diversified to address a variety of social issues. This study contributes to neglected areas of social movement research by examining the ways in which social class directly and indirectly informs the politics of a contemporary anarchist collective.
ANARCHY IN THE UNIONS: CONTEMPORARY ANARCHISTS AT WORK
Authors: Shantz Jeffrey
Published: September 2009

Few social movements in North America have enjoyed as much of a revival in the twenty‐first century as anarchism. In the years prior to the Seattle World Trade Organization (WTO) protests of 1999, and especially following the success of those demonstrations, anarchism has reemerged as a vibrant political force. Yet, little attention has been given to ongoing organizing practices undertaken by anarchists as part of struggles in communities and workplaces. The lack of informed analysis of anarchist politics has meant that the actual practices and intentions of this major, and growing, contemporary movement remain obscured.
“WE ARE ALL LEADERS”: ANARCHISM AND THE NARRATIVE OF THE INDUSTRIAL WORKERS OF THE WORLD
Authors: Christiansen Jonathan A.
Published: September 2009

This article explores the narrative relationship between the Industrial Workers of the World (IWW) as an organization and anarchism. Specifically, this article asks: How has the theme of anarchism been negotiated within the IWW and how does it appear in the narrative? In addition, how has anarchism functioned within the organizational narrative? For this research, a mixed method approach of content analysis, semi‐structured interviews, and participant observation was used. This article describes four ways in which anarchism is used in the IWW narrative. First, both the IWW and anarchism have benefited from changing structural opportunities. Second, the IWW is seen as a practical means for carrying out anarchist ideals. Third, anarchism has been a mediator for the IWW. Finally, there is tension between the IWW and anarchism.
BETWEEN ANARCHISM AND AUTONOMIST MARXISM
Authors: Gautney Heather
Published: September 2009

Anarchists and autonomist Marxists played a vital role in the development of the Alternative Globalization Movement (AGM), especially with regard to their distinct contributions and insights in the realm of strategy and organization. Despite their common anticapitalist and antiauthoritarian orientation, however, their practical and theoretical approaches to issues of organization and change remain substantially different and in some contexts have been deeply divisive. This paper explores the theoretical and practical similarities and differences between anarchists and autonomists. It begins with an analysis of the tenuous binary between “lifestyle” and “social” anarchism, primarily within the U.S., where anarchism has significantly impacted AGM activism. What follows is a discussion of autonomist movements in Italy and Germany from the 1950s onward. The article then compares both tendencies in terms of how they balance the organizational requisites for change with their desires for freedom.
Testosterone Partially Ameliorates Metabolic Profile and Erectile Responsiveness to PDE5 Inhibitors in an Animal Model of Male Metabolic Syndrome
Authors: Filippi Sandra , Vignozzi Linda , Morelli Annamaria , Chavalmane Aravinda K. , Sarchielli Erica , Fibbi Benedetta , Saad Farid , Sandner Peter , Ruggiano Peggy , Vannelli Gabriella B. , Mannucci Edoardo , Maggi Mario
Published: September 2009

Introduction

Metabolic syndrome (MetS) is a clustering of cardio-metabolic risk factors (hyperglycemia, hypertension, dyslipidemia, visceral fat accumulation) that is also associated with hypogonadism and erectile dysfunction (ED).

Aim

To clarify the relationships among MetS, hypogonadism, and ED, we developed an animal model of MetS.

Methods

Male rabbits fed a high-fat diet (HFD), with or without testosterone (T) supplementation, were compared with control rabbits (fed a standard chow) and with rabbits made hypogonadal by a single injection of a long-acting GnRH-analog, triptorelin.

Main Outcome Measures

Evaluation of metabolic disturbances (plasma glucose, cholesterol, triglycerides, testosterone, LH, FSH level, glucose tolerance, mean arterial pressure, visceral fat accumulation), and corpora cavernosa (CC) relaxant capacity (in vitro contractility study) in HFD animals as compared with control, GnRH analog-treated rabbits, and T-supplemented HFD rabbits.

Results

HFD rabbits showed all the features of MetS. HFD induced hypogonadotropic hypogonadism is characterized by a reduction of plasma T, FSH, LH levels, testis and seminal vesicles weight, and testicular steroidogenic enzymes. Such a phenotype is similar to that induced by triptorelin administration. A reduced GnRH immunopositivity in hypothalamus suggests a central origin of HFD-related hypogonadism. HFD also induced penile alterations, as demonstrated by a reduction of acetylcholine-and electrical field stimulation-induced CC relaxation, hyper-responsiveness to the NO donor, SNP, and unresponsiveness to PDE5 inhibitors. Similar penile alterations were observed in triptorelin treated rabbit. In HFD, as well as in triptorelin treated rabbits, PDE5 and eNOS mRNA expression quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) were significantly decreased. T administration prevented almost all penile alterations observed in HFD rabbits. T treatment dramatically reduced HFD-induced visceral obesity, partially ameliorating also the metabolic profile.

Conclusion

We have developed an animal model of MetS associated with hypogonadotropic hypogonadism and penile alterations including unresponsiveness to PDE5 inhibitors. T supplementation was able to partially revert HFD-induced phenotype.
Vardenafil can Improve Continence Recovery after Bilateral Nerve Sparing Prostatectomy: Results of a Randomized, Double Blind, Placebo-Controlled Pilot Study
Authors: Gacci Mauro , Ierardi Alessandro , Rose Augusto Delle , Tazzioli Stefano , Scapaticci Emanuele , Filippi Sandra , Maggi Mario , Nicita Giulio , Carini Marco , Montorsi Francesco
Published: September 2009

Introduction

Phosphodiesterase type 5 inhibitors (PDE5-I) have acquired an established role in the treatment of post-prostatectomy erectile dysfunction (ED). Several trials in men with ED and lower urinary tract symptoms associated with benign prostatic hyperplasia suggest that PDE5-I could improve both erectile function and urinary symptoms.

Aim

To assess the role of vardenafil in continence recovery after bilateral nerve sparing radical prostatectomy (BNS-RP).

Methods

Thirty-nine patients with prostate cancer were recruited. After BNS-RP, patients were double-blinded assigned to three arms: a) vardenafil on demand; b) vardenafil nightly; and c) placebo.

Main Outcomes Measures

Urinary function (UF) and urinary bother (UB) of University of California–Los Angeles Prostate Cancer Index questionnaire were assessed preoperatively and at 1, 3, 6, 9, 10, and 12 months. Twelve-month outcomes were compared to 1 month with a t-test. The differences in UF and UB (at 3, 6, 9, 10, and 12 months) between the three treatment arms were calculated by an analysis of variance. With ALLFIT we estimated half-maximal recovery times (ER50) and maximal recovery (Rmax) in three groups.

Results

The improvement of UF and UB between 1 and 12 months was significant in all arms except for placebo (UF: P = 0.125; UB: P = 0.089). Nightly resulted in greater UF at 3, 6, and 9 months and greater UB at 6 months compared with placebo (P = 0.042, P = 0.044 and P = 0.039); after nightly administration, patients presented higher UB than after on-demand use, 3 and 6 months postoperatively (P = 0.036 and P = 0.017). ALLFIT demonstrated a similar ER50 in all groups (2.6 months for both UF and UB) and indicated that nightly administration induced significant improvements in Rmax compared with placebo (both <0.0001).

Conclusions

Vardenafil can improve continence recovery after BNS-RP compared with placebo. The daily use of vardenafil seems to provide better continence rate, although it does not seem to influence the timing needed to achieve full continence.
Conceptual Issues in Response‐Time Modeling
Authors: Van Der Linden Wim J.
Published: September 2009

Two different traditions of response‐time (RT) modeling are reviewed: the tradition of distinct models for RTs and responses, and the tradition of model integration in which RTs are incorporated in response models or the other way around. Several conceptual issues underlying both traditions are made explicit and analyzed for their consequences. We then propose a hierarchical modeling framework consistent with the first tradition but with the integration of their parameter structures as a second level of modeling. Two examples of the framework are presented. Also, a fundamental equation is derived which relates the RTs on test items to the speed of the test taker and the time intensity of the items. The equation serves as the core of the RT model in the framework. Finally, empirical applications of the framework demonstrating its practical value are reviewed.
Risks and benefits of parent/child bed sharing
Authors: Sobralske Mary C. , Gruber Megan E.
Published: September 2009

Purpose:To recognize the concerns for and against parent/child bed‐sharing (co‐sleeping) practices.

Data sources:Review of the literature and the clinical experiences of the authors.

Conclusions:The decision to bed share ultimately lies with the parent, but it is the responsibility of the nurse practitioner (NP) to discuss risks and benefits of parent preferences and to help families make a safe decision regarding the sleeping arrangement for their child.

Implications for practice:If NPs know the benefits and risks regarding co‐sleeping and bed sharing, they can better promote safe and culturally congruent family centered care.
Emerging concepts in cardiovascular disease risk assessment: Where do women fit in?
Authors: Gleeson Deborah , Crabbe Deborah L.
Published: September 2009

Purpose: To highlight the current limitations in the assessment of cardiovascular disease (CVD) risk for women. This article will offer the reader information on the current process for assessing CVD risk in women, the pitfalls associated with this current strategy, and the role of novel risk factors.

Data sources: Extensive review of the medical literature in the area of women's cardiovascular health.

Conclusions: The assessment of CVD risk for women is currently an evolving science. Limitations in the ability of the Framingham score to accurately estimate risk in women from diverse populations are increasingly recognized. Vastly different treatment goals between the genders for similar levels of risk factors have led to a re‐evaluation of this strategy in women. While the Framingham score is still useful for guiding cholesterol treatment goals, the current preventive guidelines for women emphasize assessing a woman's risk throughout her lifetime. The future development of tools for improved risk stratification that incorporate novel risk factors may in fact improve our ability to appropriately risk stratify women to evidence‐based therapies.

Implications for practice: Utilizing the Framingham Risk Assessment Tool and further CVD risk stratification using novel markers such as high sensitivity C‐reactive protein, family history, and functional capacity may identify unique subsets of women at higher risk for CVD. Nurse practitioners can be instrumental in this assessment, education, and treatment of women at risk for CVD.
Level of autonomy of primary care nurse practitioners
Authors: Bahadori Alex , Fitzpatrick Joyce J.
Published: September 2009

Purpose: The purpose of this descriptive study was to determine the level of autonomy of nurse practitioners (NPs) providing care to patients in a primary care setting.

Data sources: Data were collected from 48 primary care NPs (PCNPs) who attended a state clinical conference. The Dempster Practice Behavior Scale (DPBS) was used to measure the autonomy of the NPs.

Conclusions: The total mean score for the DPBS in this study was 127 (SD = 10.25), indicating a very high level of autonomy of the NPs. The Empowerment subscale had the lowest overall mean score, and the Valuation subscale had the highest. There was no statistically significant relationship between level of autonomy and age, years worked as an RN, and years worked as an NP.

Implications for practice: This study provided evidence that PCNPs are highly autonomous professionals and continue to struggle with empowerment. NPs educationally prepared with a better knowledge of legal and political issues will be better suited to influence healthcare reform. NPs, as autonomous professionals, will be more likely to impact and shape future healthcare policy.
Culturally tailored education to promote lifestyle change in Mexican Americans with type 2 diabetes
Authors: Vincent Deborah
Published: September 2009

Purpose: The purpose of this article is to report the results of a culturally tailored diabetes intervention for Mexican Americans on physical activity and to report the results of a focus group with intervention participants.

Data sources: Seventeen Mexican American subjects with type 2 diabetes participated in the study. The study used a pretest/posttest control group design with 10 subjects in each group (N = 20). Outcome measures included the number of steps walked weekly, weight, and body mass index (BMI). Pedometers were used to measure the daily number of steps in the intervention group. A focus group provided data on participant satisfaction.

Conclusions: Results suggest a positive effect of the intervention on physical activity level, weight, and sense of control over diabetes self‐management. Intervention participants had a statistically significant increase in the number of steps walked per day and a statistically significant mean weight loss of five pounds. Focus group results indicate that participants were satisfied with the culturally tailored intervention and that they and their families benefited from the intervention.

Implications for practice: A culturally tailored diabetes self‐management program may result in improved outcomes for Mexican Americans with type 2 diabetes.
Female sexual dysfunction: A primary care perspective
Authors: Zakhari Raymond
Published: September 2009

Purpose: To discuss the incidence and prevalence of sexual dysfunction among women, some common etiologies, and patient–provider relationships that seem to inhibit successful resolution of female sexual dysfunction.

Data sources: A selective review of the literature on female sexual dysfunction, and an overview of assessment tools that can be used to evaluate and monitor its treatment.

Conclusion: Sexual dysfunction in women is a health issue often overlooked by medical personnel, but it is a topic of great importance to both the patient and her sexual partner(s). It has been well established that quality of sex, that is, satisfaction with one's sex life, is a major quality‐of‐life indicator. But specifically as concerns the female patient, the issue has been overlooked by much of the healthcare community, perhaps because the topic of female sexual dysfunction is multifaceted and complex in nature.

Implications for practice: Clinicians have an obligation to develop self‐awareness and clinical intuition to address the topic in the utmost professional manner.
A Dynamic Approach to the Determinants of Immigrants’ Language Proficiency: The United States, 1980–2000
Authors: van Tubergen Frank , Kalmijn Matthijs
Published: September 2009

This article proposes a dynamic perspective on immigrants’ language proficiency. Hypotheses are formulated about immigrants’ language skills at arrival and about the speed with which immigrants learn the language thereafter. It pools data from the 1980, 1990, and 2000 U.S. Censuses, and uses a synthetic cohort design to analyze the language skills of immigrants within the first 20 years after migration. Multilevel models show that higher educated immigrants arrive with better language skills and learn the language quicker. Group size has a double-negative effect: it attracts less skilled immigrants, and it hampers language learning. These and other determinants are discussed in light of current research on immigrants’ second-language proficiency.
Why is There So Little Migrant Settlement in East Asia?
Authors: Seol Dong-Hoon , Skrentny John D.
Published: September 2009

Unlike states in Europe, East Asia settles very few migrants and has not developed a European-style multicultural society. We seek to explain this variation using comparative analysis of two of the most advanced states in East Asia, South Korea and Japan, with several states in Europe. Focusing on family reunification - almost always the precursor to migrant settlement - we examine the effects of several independent variables, including supranational institutions, independent courts, interest groups, political culture, and the perceptions of migrants. We conclude that both Korea and Japan have less migrant settlement because of the lack of regional institutions pushing for family reunification rights, an elite political culture that still maintains the assumptions and repertoires of a “developmental state,” where rights may be sacrificed for economic growth and order, and migrant perceptions of greater immigration control in Asia.
Mechanisms of fibrinogen‐induced microvascular dysfunction during cardiovascular disease
Authors: Lominadze D. , Dean W. L. , Tyagi S. C. , Roberts A. M.
Published: September 2009

Fibrinogen (Fg) is a high molecular weight plasma adhesion protein and a biomarker of inflammation. Many cardiovascular and cerebrovascular disorders are accompanied by increased blood content of Fg. Increased levels of Fg result in changes in blood rheological properties such as increases in plasma viscosity, erythrocyte aggregation, platelet thrombogenesis, alterations in vascular reactivity and compromises in endothelial layer integrity. These alterations exacerbate the complications in peripheral blood circulation during cardiovascular diseases such as hypertension, diabetes and stroke. In addition to affecting blood viscosity by altering plasma viscosity and erythrocyte aggregation, growing experimental evidence suggests that Fg alters vascular reactivity and impairs endothelial cell layer integrity by binding to its endothelial cell membrane receptors and activating signalling mechanisms. The purpose of this review is to discuss experimental data, which demonstrate the effects of Fg causing vascular dysfunction and to offer possible mechanisms for these effects, which could exacerbate microcirculatory complications during cardiovascular diseases accompanied by increased Fg content.
CpG ODN Enhances the Efficacy of Rituximab in Non‐Hodgkin Lymphoma
Authors: Buhé Virginie , Guerrier Thomas , Youinou Pierre , Berthou Christian , Loisel Séverine
Published: September 2009

The anti‐CD20 monoclonal antibody rituximab (RTX) has been applied to the therapy of B‐cell proliferative disease, but a number of factors, such as the expression level of its target antigen, modulate its efficacy. Since unmethylated CpG‐containing DNA sequences activate members of the immune systems, including B lymphocytes, their benefit to RTX treatment was determined on human lymphoma B‐cell line cells. These Daudi cells expressed high endosomal level of the CpG Toll‐like receptor 9, but CpG had effects neither on the viability, nor on the proliferation of the cells. In contrast, there appeared to be an increase in the expression of CD20, resulting in a higher efficiency of RTX for the killing of malignant Daudi cells.
Treatment of Rat Adjuvant Arthritis with Flavonoid (Detralex®), Methotrexate, and Their Combination
Authors: Rovenský Jozef , Stančíková Mária , Rovenská Emília , Štvrtina Svetoslav , Štvrtinová Viera , Švík Karol
Published: September 2009

In both adjuvant arthritis and rheumatoid arthritis, edema and inflammation appear in synovial joints. Edema or effusion reflects an imbalance in lymph dynamics. Purified micronized flavonoid fraction is mainly used in the treatment of chronic venous insufficiency. This compound improves lymphatic drainage with a significant increase in lymphatic flow and lymphatic pulsality. It is suggested that the beneficial effect of purified micronized flavonoid fraction may be involved in the treatment of adjuvant arthritis in rats. In this study treatment of adjuvant arthritis in rats with Detralex, methotrexate, and their combination were evaluated. Groups of rats with adjuvant arthritis were treated with methotrexate (0.6 mg/kg/week), Detralex (20 mg/kg/day), and their combination for 50 days from adjuvant application. Hind paw swelling, arthrogram scores, serum albumin level, serum nitrite/nitrate concentrations, and whole‐body mineral density were evaluated as markers of inflammation and destructive changes associated with arthritis. Long‐term prophylactic treatment with low‐dose methotrexate significantly inhibited the markers of both inflammation and arthritis. Detralex administered alone slightly decreased both the hind paw swelling and the arthritic score. Other inflammatory and arthritic markers were not significantly influenced. However, Detralex combined with methotrexate markedly potentiated the beneficial effects of methotrexate, which resulted in a more significant reduction in hind paw swelling, arthritic scores, and serum concentrations of nitrite/nitrate. Interestingly, the arthritis‐induced decrease of bone mineral density in AA rats was significantly lower only in the group treated with the combination of Detralex and methotrexate. Our results indicate that Detralex increased the therapeutic efficacy of methotrexate basal treatment in AA. We suggest that this may be related to the beneficial effect of Detralex on microcirculation, especially on venules and lymphatic vessels.
Defensins in Systemic Lupus Erythematosus
Authors: Froy Oren , Sthoeger Zev M.
Published: September 2009

Systemic lupus erythematosus (SLE) is an autoimmune disease, resulting in inflammation and tissue damage. The precise etiology for SLE is so far unknown. It has been shown that the innate immunity plays a role in SLE pathogenesis. The innate immune system confers broad protection against pathogens by the secretion of broad‐spectrum antibacterial and immunomodulatory substances named defensins. Recently, α‐defensin, the products of neutrophils have been found to be upregulated at the mRNA and protein levels in SLE patients. In addition, increased antidefensin antibodies were found in sera of patients with SLE, but these levels decreased after therapy with corticosteroids. These recent findings suggest a role for defensins in the pathogenesis of SLE. Thus, activation and degranulation of neutrophils leads to α‐defensin secretion in SLE patients. Given their immunomodulatory role, α‐defensin secretion might activate the adaptive immune system leading to the stimulation of the immune system, as is manifested in SLE.
Antibodies to Neurofilaments
Authors: Talja Ija , Reimand Tiia , Uibo Oivi , Reimand Koit , Aun Silver , Talvik Tiina , Janmey Paul A. , Uibo Raivo
Published: September 2009

Immune responses to neuronal proteins are a frequent occurrence in neurodegenerative diseases. This study determines the occurrence of autoantibodies to the three neurofilament subunits in phosphorylated and dephosphorylated forms and relates these measures to age, human leukocyte antigen (HLA), and severity of disease in Down syndrome (DS). IgG‐type antibodies to three neurofilament (NF) subunits, NF‐L, NF‐M, and NF‐H, in both phosphorylated and dephosphorylated forms were tested by immunoblot in 128 patients with DS and compared to antibody levels in 94 normal controls. DS was revealed by karyotype analysis. Antibodies to dephospho‐NF‐M, NF‐M, and NF‐L were more common in DS samples than in controls. Total pools of DS and control samples had similar frequency of antibodies to NF‐H, but there was a higher prevalence of antibodies against NF‐H in DS patients with moderate or mild disability (43.0%) compared with those having serious disability (14.3%). No NF‐H antibody was seen among young children (age 14 years or younger) of the latter group. The HLA‐DR15 allele was negatively correlated with antibodies against NF‐H. The high prevalence of antibodies to neurofilament proteins and the differences between DS and control samples may reflect the cross‐talk between neural and immune systems that could have an important role in defending neural structures from neurodegenerative processes. In children with DS the presence of antibodies to NF‐H might reflect a more favorable prognosis.
B Cell Depletion in Early Rheumatoid Arthritis: A New Concept in Therapeutics
Authors: Renato Guzman M.
Published: September 2009

Rheumatoid arthritis is a severe, aggressive, and debilitating disease that has a high mortality rate. There have been considerable advances in the last few years as a result of developments in molecular biology, immunology, and biotechnology. The knowledge about the elements that directly participate in the genesis of the disease has been established. Nowadays, treatments are more rational and are directed to specific targets. Anticytokine agents, especially therapies that target tumor necrosis factor (TNF), are considered to be frontline biological agents for the treatment of rheumatoid arthritis. The blocking of lymphocyte B with rituximab, a genetically engineered chimerical monoclonal antibody, has been approved by the US Food and Drug Administration as a treatment in patients with rheumatoid arthritis who have severe disease not responding to conventional multiple therapies and to TNF‐blocker agents. We propose that patients with severe aggressive rheumatoid arthritis could benefit from rituximab without previous exposure to anti‐TNF agents as a biological agent, and we postulate that rituximab could be used as a first‐line biological agent in this subgroup. We present our recent experience with patients having severe and active rheumatoid disease with whom we used rituximab as a first‐line biological agent.
Genetic Susceptibility Loci in Rheumatoid Arthritis Establish Transcriptional Regulatory Networks with Other Genes
Authors: Silva Guilherme Liberato , Junta Cristina Moraes , Sakamoto‐Hojo Elza Tiemi , Donadi Eduardo Antonio , Louzada‐Junior Paulo , Passos Geraldo A. S.
Published: September 2009

Linkage studies have identified the human leukocyte antigen (HLA)‐DRB1 as a putative rheumatoid arthritis (RA) susceptibility locus (SL). Nevertheless, it was estimated that its contribution was partial, suggesting that other non‐HLA genes may play a role in RA susceptibility. To test this hypothesis, we conducted microarray transcription profiling of peripheral blood mononuclear cells in 15 RA patients and analyzed the data, using bioinformatics programs (significance analysis of microarrays method and GeneNetwork), which allowed us to determine the differentially expressed genes and to reconstruct transcriptional networks. The patients were grouped according to disease features or treatment with tumor necrosis factor blocker. Transcriptional networks that were reconstructed allowed us to identify the interactions occurring between RA SL and other genes, for example, HLA‐DRB1 interacting with FNDC3A (fibronectin type III domain containing 3A). Given that fibronectin fragments can stimulate mediators of matrix and cartilage destruction in RA, this interaction is of special interest and may contribute to a clearer understanding of the functional role of HLA‐DRB1 in RA pathogenesis.
Autoantibody Standardization in the Netherlands
Authors: Damoiseaux Jan , Tervaert Jan Willem Cohen , Derksen Ronald , Hamann Dörte , Hooijkaas Herbert , Klasen Ina , Kallenberg Cees , Limburg Pieter , Smeenk Ruud
Published: September 2009

Several initiatives have been undertaken, independent of the European Autoantibody Standardization Initiative (EASI), to standardize autoantibodies in the Netherlands. The Dutch EASI team has made an inventory of which initiatives on autoantibody standardization are already available and what future plans for autoantibody standardization exist. This inventory will subsequently be used to define what may be addressed by the Dutch EASI team. The Diagnostic Compass, initiated by the association of Dutch health insurance companies, describes methods and relevance of laboratory tests, including autoantibody tests. Recently, this initiative has been taken over by an independent publisher. There is also a national organization involved in developing guidelines in medicine, including guidelines for autoantibody testing. In addition, there is a national foundation for quality assessment in clinical laboratories (SKML). The quality assessment includes a wide array of autoantibodies. Samples are collected and thoroughly investigated by reference laboratories. Interpretation of results and advice to clinicians are part of the program. Feedback on the results of this proficiency testing is given in reports and during meetings to discuss trends, technical issues, and new developments. The last initiative that we discuss is the foundation Referentie Laboratorium Reuma Serologie (RELARES), which was founded to standardize serology in rheumatic diseases by preparing standard sera. Recently, RELARES has been combined with SKML. A new SKML working group, Standardization Autoimmune Serology, has been initiated to continue the work of RELARES. When comparing the already available Dutch initiatives to the international EASI goals, there appears to be a lack of harmonization in testing algorithms, and this issue is the most important topic to be addressed in the near future.
Shared and Unique Gene Expression in Systemic Lupus Erythematosus Depending on Disease Activity
Authors: Sandrin‐Garcia Paula , Junta Cristina Moraes , Fachin Ana L. , Mello Stephano S. , Baião Ana Maria T. , Rassi Diane M. , Ferreira Márcia C. T. , Trevisan Glauce L. , Sakamoto‐Hojo Elza T. , Louzada‐Júnior Paulo , Passos Geraldo A. S. , Donadi Eduardo A.
Published: September 2009

Patients presenting with active systemic lupus erythematosus (SLE) manifestations may exhibit distinct pathogenetic features in relation to inactive SLE. Also, cDNA microarrays may potentially discriminate the gene expression profile of a disease or disease variant. Therefore, we evaluated the expression profile of 4500 genes in peripheral blood lymphocytes (PBL) of SLE patients. We studied 11 patients with SLE (seven with active SLE and four with inactive SLE) and eight healthy controls. Total RNA was isolated from PBL, reverse transcribed into cDNA, and postlabeled with Cy3 fluorochrome. These probes were then hybridized to a glass slide cDNA microarray containing 4500 human IMAGE cDNA target sequences. An equimolar amount of total RNA from human cell lines served as reference. The microarray images were quantified, normalized, and analyzed using the R environment (ANOVA, significant analysis of microarrays, and cluster‐tree view algorithms). Disease activity was assessed by the SLE disease activity index. Compared to the healthy controls, 104 genes in active SLE patients (80 repressed and 24 induced) and 52 genes in nonactive SLE patients (31 induced and 21 repressed) were differentially expressed. The modulation of 12 genes, either induced or repressed, was found in both disease variants; however, each disease variant had differential expression of different genes. Taken together, these results indicate that the two lupus variants studied have common and unique differentially expressed genes. Although the biological significance of the differentially expressed genes discussed above has not been completely understood, they may serve as a platform to further explore the molecular basis of immune deregulation in SLE.
Reversing Bacteria‐induced Vitamin D Receptor Dysfunction Is Key to Autoimmune Disease
Authors: Waterhouse Joyce C. , Perez Thomas H. , Albert Paul J.
Published: September 2009

Vitamin D research is discussed in light of the hypothesis that the lower average levels of vitamin D frequently observed in autoimmune disease are not a sign of deficiency. Instead, it is proposed that the lower levels result from chronic infection with intracellular bacteria that dysregulate vitamin D metabolism by causing vitamin D receptor (VDR) dysfunction within phagocytes. The VDR dysfunction causes a decline in innate immune function that causes susceptibility to additional infections that contribute to disease progression. Evidence has been accumulating that indicates that a number of autoimmune diseases can be reversed by gradually restoring VDR function with the VDR agonist olmesartan and subinhibitory dosages of certain bacteriostatic antibiotics. Diseases showing favorable responses to treatment so far include systemic lupus erythematosis, rheumatoid arthritis, scleroderma, sarcoidosis, Sjogren's syndrome, autoimmune thyroid disease, psoriasis, ankylosing spondylitis, Reiter's syndrome, type I and II diabetes mellitus, and uveitis. Disease reversal using this approach requires limitation of vitamin D in order to avoid contributing to dysfunction of nuclear receptors and subsequent negative consequences for immune and endocrine function. Immunopathological reactions accompanying bacterial cell death require a gradual elimination of pathogens over several years. Practical and theoretical implications are discussed, along with the compatibility of this model with current research.
New Developments in Serodiagnosis of Childhood Celiac Disease
Authors: Prause Christian , Richter Thomas , Koletzko Sibylle , Uhlig H. Holm , Hauer Almuthe C. , Stern Martin , Zimmer Klaus‐Peter , Laass Martin W. , Probst Christian , Schlumberger Wolfgang , Mothes Thomas
Published: September 2009

Antibodies to deamidated gliadin present a new tool in the diagnosis of celiac disease (CD). In children, the ELISA for the determination of IgG antibodies to (deamidated) gliadin‐analogous fusion peptides (GAF3X) has a superior performance compared to the ELISA for the determination of antibodies against native gliadin and is comparable to assays for IgA antibodies against tissue transglutaminase (IgA‐anti‐tTG). The combined investigation of IgG antibodies to GAF3X (IgG‐anti‐GAF3X) and IgA‐anti‐tTG significantly increases the fraction of children definitely identified as either CD or non‐CD patients. The new IgG‐anti‐GAF3X ELISA was also able to detect CD in three cases of IgA deficiency and in two cases of latent CD and was also useful in the diagnosis of children younger than 2 years of age.
Prevalence of Anticardiolipin Antibodies in Patient Cohorts with Distinct Clinical Manifestations of the Antiphospholipid Syndrome
Authors: Damoiseaux Jan , Peeters Louis , Hupperts Raymond , Boreas Anita , Ten Cate Hugo , Tervaert Jan Willem Cohen
Published: September 2009

Clinical manifestations of antiphospholipid syndrome (APS) vary from venous and arterial thrombosis to pregnancy loss and pre‐eclampsia (PEC). Our aims were to establish the prevalence of anticardiolipin antibodies (aCLA) in patients with clinical features of APS and to compare the reference ELISA method with the novel automated EliA aCLA assay. Serum samples from 1278 patients with either deep venous thrombosis (DVT), young stroke (YS), PEC, or multiple sclerosis (MS) were included. The latter cohort was included because initial presentation of APS might resemble MS. Using the internationally accepted cutoff level of 40 MPL/GPL [IgM antiphospholipid units/mL (MPL)/IgG antiphospholipid units/mL (GPL)], 0.7% and 0.5% of the samples were positive for IgM and IgG aCLA by ELISA, respectively. Using the cutoff level recommended by the manufacturer (15 MPL/GPL), the prevalence was 2.7% and 2.8%, respectively. The prevalence by EliA was 2.0% and 0.5% for IgM and IgG aCLA, respectively (40 MPL/GPL cutoff). However, with a low cutoff level, the prevalence of IgM aCLA, but not IgG aCLA, was higher in the DVT (14.3%), YS (14.6%), and PEC (17.7%) cohorts but not the MS cohort. The prevalence of aCLA was too low for reliable determination of concordance between assays. In patients with DVT, CVA, PEC, and MS, the prevalence of aCLA is low, in particular when internationally accepted cutoff values are applied. Our finding questions the efficacy of aCLA testing. Therefore, there might be either a need for defining specific clinical criteria to obtain a better rational for aCLA testing or aCLA testing should be excluded from the classification criteria.
Influence of Statins on MHC Class I Expression
Authors: Singh Pratibha , Kohr Danielle , Kaps Manfred , Blaes Franz
Published: September 2009

Statins, inhibitors of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase, are widely prescribed for their cholesterol‐lowering properties to reduce atherogenesis and cardiovascular morbidity. However, compelling evidence exists that statins also have extensive immunomodulatory properties that operate independently of lipid lowering. Consequently, much attention has been directed toward their immunomodulatory effect and their potential as therapeutic agents for the treatment of autoimmune diseases. Statins have the ability to modulate a broad range of proinflammatory immune mechanisms through inhibition of small GTPases and other prenylated proteins. One of the statins’ immunomodulatory effects is downregulation of MHC class II expression. In contrast, patients with statin‐induced myopathy show high MHC class I expression. In this review, the effect of statins on MHC class I expression is reviewed alongside statins’ effect on immune function.
Cytokines and Anxiety in Systemic Lupus Erythematosus (SLE) Patients Not Receiving Antidepressant Medication
Authors: Figueiredo‐Braga Margarida , Mota‐Garcia Fernando , O’Connor José‐Enrique , Garcia Juan Rafael , Mota‐Cardoso Rui , Cardoso Carla Sofia , De Sousa Maria
Published: September 2009

Autoimmunity travelled from the theoretical roots planted by Burnet with the clonal selection theory and the early finding of a mouse providing a test for the role of the thymus as a source of forbidden clones. This chapter briefly reviews early work with the NZB mouse and presents results of an analysis of associations between cytokines and physical and psychometric parameters in systemic lupus erythematosus (SLE) patients not medicated with antidepressants. Some cytokines, particularly IFN‐γ, relate significantly to physical symptoms and anxiety. We conclude with the speculation that anxiety is linked to innate immunity and more severe neuropsychiatric disease in SLE to adaptive immunity.
Possible Involvement of Chemokine‐induced Platelet Activation in Thrombophilic Diathesis of Antiphospholipid Syndrome
Authors: Kubota Tetsuo , Fukuya Yasuko , Hashimoto Rieko , Kanda Takashi , Suzuki Hidenori , Okamura Yosuke , Nanki Toshihiro , Miyasaka Nobuyuki , Umezawa Kazuo
Published: September 2009

Among the heterogeneous antiphospholipid antibodies, many studies suggest that those directed to β2‐glycoprotein I (β2GPI) are the major pathogenic antibodies in antiphospholipid syndrome (APS). They have been shown to activate the coagulation pathway via several mechanisms, activate platelets via thrombin formation, and suppress fibrinolysis. Additionally, we propose another possible mechanism that involves certain chemokines and results in platelet activation. This hypothesis is based on the observations that anti‐β2GPI antibodies stimulated monocytes to secrete inflammatory cytokines such as IL‐1β and TNF‐α, which in turn stimulated vascular endothelial cells to express chemokines such as CX3CL1 and CCL5. CX3CL1 increased the ability of normal platelets to adhere to collagen at a high shear rate, while CCL5 induced platelet aggregation. Expression of tissue factor, IL‐1β, and TNF‐α by monocytes stimulated with anti‐β2GPI antibodies, as well as CX3CL1 and CCL5 by vascular endothelial cells stimulated with IL‐1β or TNF‐α were all suppressed by the NF‐κB–specific inhibitor DHMEQ. These results suggest that the NF‐κB pathway may be a potential therapeutic target relating to both the coagulation pathway and platelet activity.
Regulatory B Cells in Autoimmune Diseases
Authors: Lemoine Sébastien , Morva Ahsen , Youinou Pierre , Jamin Christophe
Published: September 2009

B lymphocytes contribute to the pathogenesis of autoimmune disorders since B‐cell depletion treatment improves such diseases. However, B cells seem ambivalent. Murine strains of nonorgan‐specific as well as organ‐specific autoimmune conditions present with aggravated symptoms when B cells are depleted. It is thus likely that some B cells are pathogenic while other have regulatory function. There is not only one regulatory B cell (Breg) subset, but different types of Breg cells. Regulatory function can thus be ascribed to autoreactive B cells, marginal zone B cells, transitional type 2–like B cells, or CD5+ B cells. Regulatory activity is induced only following cell activation through a B‐cell receptor, CD40, and/or TLR9. Regulatory effects are then mediated by a soluble agent, such as IL‐10, and/or direct cell‐to‐cell contacts that involve CD40 or B7 co‐stimulatory molecules. Targeted cells also vary from one disease to another. Antigen‐specific autoreactive T cells, dendritic cells, macrophages, and regulatory T lymphocytes can thus be either inhibited or activated to finally modulate the autoimmune response. Taken as a whole, it appears that Breg cells participate in the control of autoimmunity within a complex cellular network that may differ for each pathology. Adapted stimulation and control of regulatory activity would thus be a prerequisite to an efficient usage of these B cells as an alternative therapy for autoimmune diseases.
Autoantigens Identified by Screening a Human Heart cDNA Library with Acute Rheumatic Fever Sera
Authors: Towers Rebecca J. , Bolm Maike , Currie Bart J. , Chhatwal Gursharan S. , Fagan Peter K.
Published: September 2009

Acute rheumatic fever (ARF) is an autoimmune sequela of group A streptococcal infection mostly affecting school‐aged children. Recurrent episodes of ARF can result in the development of rheumatic heart disease (RHD). One in 40 indigenous Australians in the Northern Territory is affected by RHD. This disease mostly impacts young people; 45% of those who require heart valve surgery in Australia due to RHD are younger than 25 years old. ARF is characterized by autoimmune attack of the heart; therefore, the presence of the autoantibodies involved could potentially be used to diagnose ARF. To this end, a human heart cDNA library was screened with serum from a patient with ARF, and 12 autoreactive human heart antigens were identified. They include five different IgG heavy chains and a range of tissue‐specific cell‐signaling proteins, species of which have been implicated in other autoimmune diseases. Preliminary ELISA results show that ARF patients have significantly higher levels of antibodies recognizing the cardiac autoantigens than controls. These antigens are promising candidates for the development of a serological assay for the diagnosis of ARF. The nature of the proteins identified has exciting implications for future research into the pathogenesis of ARF.
Association Study on Two Vitamin D Receptor Gene Polymorphisms and Vitamin D Metabolites in Multiple Sclerosis
Authors: Smolders Joost , Damoiseaux Jan , Menheere Paul , Tervaert Jan Willem Cohen , Hupperts Raymond
Published: September 2009

Background: An association of two single‐nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) gene, Apal (rs7975232) and Taql (rs731236), with multiple sclerosis (MS) has been reported in a Caucasian population. Another SNP of the VDR gene, Fokl (rs10735810), has been associated with serum levels of 25‐hydroxyvitamin D [25(OH)D]. Objective: Since 25(OH)D status has been associated with MS incidence, we assessed the association Apal and Taql with the serum levels of 25(OH)D and 1,25(OH)2D, and MS in our population. Methods: We determined the two SNPs as well as the summer and winter period serum levels of 25(OH)D and 1,25(OH)2D in 212 MS patients. Additionally, we genotyped 289 healthy controls and determined the metabolite levels. Results: The genotype and allele distribution of the two VDR gene SNPs did not differ between patients and controls. There was no association of the Apal and Taql SNPs with 25(OH)D levels, 1,25(OH)2D levels, or 1,25(OH)2D/25(OH)D ratios in patients or controls. Discussion: We found no association of the Apal and Taql VDR gene SNPs with MS or with vitamin D metabolism in our population. Further research should assess the complex interaction between vitamin D, the VDR, and susceptibility to MS.
Choroid Plexus Connexin 43 Expression and Gap Junction Flexibility Are Associated with Clinical Features of Acute EAE
Authors: Jovanova‐Nesic K. , Koruga D. , Kojic D. , Kostic V. , Rakic L. , Shoenfeld Y.
Published: September 2009

Experimental autoimmune encephalomyelitis (EAE) induced by ventricular injection of antimyelin oligodendrocyte antibodies in DA rats showed severe clinical signs 4 to 5 days after injection. Immunocytochemically, connexin 43 (Cx43) expression increased in the choroid plexus and in the subventricular and subgranular zones of the hippocampus during the development of acute EAE, and decreased after the beginning of the remission phase of the disease. Quantitative computing analysis showed a significantly increased Cx43 expression in the choroid plexus at the peak of the disease. Plaque‐pattern expression of the Cx43 in the choroid plexus (CP) of acute EAE correlated with the increased docking and coupling of the Cx43 hemichannels revealed by atomic force microscopy (AFM). The inner diameter of the gap junction (GJ) channels decreased in the CP of acute EAE, measured by AFM. Cell structure conformational changes showed influences the channels' flexibility in acute EAE.
Autoimmunity Triggers in the NOD Mouse
Authors: Côrte‐Real Joana , Duarte Nádia , Tavares Luís , Penha‐Gonçalves Carlos
Published: September 2009

The nonobese diabetic mouse (NOD) is widely used as a model to study human type 1 diabetes (T1D). In the NOD mouse T1D is a T cell–mediated autoimmune disease of complex etiology in which B cells play an essential role. One of the major unresolved issues in T1D is the genetic and/or environmental factors that trigger the autoimmune reaction. In the NOD mouse, as in humans, auto‐antibodies to pancreatic islets are present at early ages and are highly correlated to diabetes progression, but their etiological role has long been disputed. NOD auto‐antibodies have the characteristics of a natural repertoire, and B1 cells, the main natural antibody producers, exhibit functional differences in this strain that could have consequences for disease determination. Using a genetic approach, we propose to test if the NOD natural auto‐antibody repertoire includes innate reactivities that participate in diabetes pathogenesis by promoting insulitis initiation.