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1.  Kitasato symposium 2010: new prospects for cytokines 
The Second Kitasato Symposium: New Prospects for Cytokines brought together researchers and rheumatologists to consider the essential role of cytokines in health and their contributions to autoimmunity. Topics addressed during the Symposium - which was held in Berlin, Germany from 27 to 29 May 2010 - included established and new cytokine targets in arthritis and autoimmunity and innovative aspects of osteoimmunology as well as current perspectives from translational and clinical studies. The keynote lecture, delivered by George Kollias, focused on insights gained from animal models into the mechanisms of TNF function in chronic inflammation and autoimmunity. The presentations at the Symposium resulted in productive discussions regarding potential new targets for the treatment of rheumatoid arthritis and other autoimmune disorders.
PMCID: PMC3046527  PMID: 21235827
2.  Distinct contribution of IL-6, TNF-α, IL-1, and IL-10 to T cell–mediated spontaneous autoimmune arthritis in mice 
Journal of Clinical Investigation  2004;114(4):582-588.
Cytokines play key roles in spontaneous CD4+ T cell–mediated chronic autoimmune arthritis in SKG mice, a new model of rheumatoid arthritis. Genetic deficiency in IL-6 completely suppressed the development of arthritis in SKG mice, irrespective of the persistence of circulating rheumatoid factor. Either IL-1 or TNF-α deficiency retarded the onset of arthritis and substantially reduced its incidence and severity. IL-10 deficiency, on the other hand, exacerbated disease, whereas IL-4 or IFN-γ deficiency did not alter the disease course. Synovial fluid of arthritic SKG mice contained high amounts of IL-6, TNF-α, and IL-1, in accord with active transcription of these cytokine genes in the afflicted joints. Notably, immunohistochemistry revealed that distinct subsets of synovial cells produced different cytokines in the inflamed synovium: the superficial synovial lining cells mainly produced IL-1 and TNF-α, whereas scattered subsynovial cells produced IL-6. Thus, IL-6, IL-1, TNF-α, and IL-10 play distinct roles in the development of SKG arthritis; arthritogenic CD4+ T cells are not required to skew to either Th1 or Th2; and the appearance of rheumatoid factor is independent of joint inflammation. The results also indicate that targeting not only each cytokine but also each cell population secreting distinct cytokines could be an effective treatment of rheumatoid arthritis.
PMCID: PMC503774  PMID: 15314695
3.  Princess Takamatsu Symposium on DNA Repair and Human Cancers 
Cancer research  2010;70(11):10.1158/0008-5472.CAN-10-0320.
The 40th International Symposium of the Princess Takamatsu Cancer Research Fund, entitled “DNA Repair and Human Cancers” was held on November 10–12, 2009 at Hotel Grand Palace, Tokyo, Japan. The meeting focused on the role of DNA repair in preventing mutations by endogenous and exogenous DNA damage and increasing the efficacy of chemotherapeutic agents by interfering with DNA repair. The fourteen presentations by the speakers from U.S.A., four from U.K., one each from Italy, The Netherlands and France, and thirteen from Japan, covered most aspects of DNA repair spanning DNA damage, molecular structures of repair enzymes, and clinical studies on inhibition of DNA repair processes. Extensive time was reserved for discussions with the active participation of the 150 invited Japanese scientists. The choice of a symposium on DNA repair in human cancers resulted in part from the excellent basic and clinical studies that have been carried out for many years in Japan, and the general lack of recognition vs. the importance of DNA repair in understanding carcinogenesis.
PMCID: PMC3846349  PMID: 20460534
4.  Tocilizumab for the Treatment of Rheumatoid Arthritis and Other Systemic Autoimmune Diseases: Current Perspectives and Future Directions 
Interleukin (IL)-6 is a cytokine featuring redundancy and pleiotropic activity. While IL-6, when transiently produced, contributes to host defense against acute environmental stress, continuous dysregulated IL-6 production plays a significant pathological role in several systemic autoimmune diseases. In response to the expectation that IL-6 blockade would constitute a novel therapeutic strategy for the treatment of these diseases, tocilizumab, a humanized anti-IL-6 receptor antibody, was developed. Clinical trials have verified the efficacy and the safety of tocilizumab for patients with rheumatoid arthritis, resulting in approval of this innovative biologic for the treatment of rheumatoid arthritis in more than 90 countries worldwide. Pathological analyses of the effect of IL-6 on the development of autoimmune diseases and a considerable number of case reports and pilot studies have also indicated the beneficial effects of this antibody on other systemic autoimmune diseases, including systemic lupus erythematosus, systemic sclerosis, polymyositis, and large-vessel vasculitis.
PMCID: PMC3270395  PMID: 22315615
5.  Open questions in autoimmunity: discussions from the 2013 Controversies in Rheumatology and Autoimmunity Meeting 
BMC Medicine  2014;12:50.
The recent CORA (Controversies in Rheumatology and Autoimmunity) meeting held in 2013 represented a unique opportunity for rheumatologists to address several topics. Among these, four topics include: (i) the role of epigenetic changes in the pathogenesis of rheumatoid arthritis (RA), as shown by studies in monozygotic twins; (ii) the cardiovascular and atherosclerotic risk in patients with RA treated with biologics; (iii) the use of new biomarkers for the diagnosis and follow-up of RA and other autoimmune diseases, as represented by the new automatic machines for anti-nuclear antibodies detection, or ultrasound imaging to follow RA progression; and (iv) the latest guidelines on how to use and manage biologic therapies in RA and other autoimmune diseases, such as lupus. In summary, we will herein present these topics of discussion and underline the conclusions obtained by rheumatologists during the 2013 CORA Meeting.
PMCID: PMC3984700  PMID: 24642104
Anti-nuclear antibodies; Atherosclerosis; Cardiovascular system; DNA methylation; microRNA; Rheumatoid arthritis; Ultrasonography
6.  The rationale for the current boom in anti-TNFα treatment. Is there an effective means to define therapeutic targets for drugs that provide all the benefits of anti-TNFα and minimise hazards? 
Annals of the Rheumatic Diseases  1999;58(Suppl 1):I27-I31.
Progress in understanding mechanisms of disease are necessary to usher in major changes in treatment. A new era in rheumatoid arthritis (RA) and related chronic autoimmune/inflammatory diseases is now beginning, with a variety of anti-TNFα treatments licensed for use in both RA and Crohn's disease. The rationale for this new treatment lies in an understanding that cytokines are critical, rate limiting molecules lying at the heart of the chronic autoimmune/inflammatory disease process. This understanding was developed from the critical evaluation of a hypothesis that was proposed linking cytokines, antigen presentation and autoimmunity in 1983. Detailed analysis focusing on the major site of the disease, the rheumatoid synovium was essential to developing indications that blockade of TNFα might be efficacious. This clue was validated using anti-TNFα treatment of an animal model of RA, murine collagen induced arthritis, and by immunohistochemical demonstration of upregulated TNF and TNF-R expression in the synovium. With this three pronged rationale, the authors were able to convince Centocor, Inc, which had developed a chimaeric anti-TNFα antibody for use in sepsis, to work with them to test the concept that TNFα blockade would be beneficial in RA. With the success of that first trial, other companies have subsequently tested their anti-TNF strategies successfully. Current interests extend to understanding the processes that regulate TNF production in the rheumatoid joint. Progress in this area is discussed, using adenoviruses to infect normal macrophages and rheumatoid synovium.

PMCID: PMC1766587  PMID: 10577970
7.  Janus kinase Inhibitors in autoimmune diseases 
Annals of the rheumatic diseases  2013;72(0 2):ii111-ii115.
Biological therapies directed at proinflammatory cytokines have irrevocably changed the landscape of treatment of rheumatoid arthritis (RA) and other autoimmune diseases. With the advances in our knowledge in cytokine signaling, the question emerges whether targeting intracellular signaling might also be a safe and efficacious strategy. Janus kinases or Jaks are critical for a large family of cytokines and the first Jak inhibitor has been approved by the FDA for the treatment of myelofibrosis. Late phase clinical trials have been completed for another Jakinib in RA. It is therefore timely to consider this new category of drugs and reflect on their potential roles, present and future, in the treatment of RA and related disorders.
PMCID: PMC3616338  PMID: 23532440
8.  Role of IL-17 in the Pathogenesis of Rheumatoid Arthritis 
Current rheumatology reports  2009;11(5):365-370.
IL-17 (also known as IL-17A) is the signature cytokine of the newly-described “Th17” T helper cell population, and has been implicated in the pathogenesis of numerous autoimmune diseases including rheumatoid arthritis. IL-17 is the founding member of a new subclass of cytokines that have highly pro-inflammatory properties. Studies in rodents, mammalian cell culture systems as well as clinical settings support a role for IL-17 in promoting rheumatoid arthritis. The history of the discovery of Th17 cells, the potential mechanisms of action of IL-17 in autoimmunity and perspectives for IL-17-targeted cytokine therapy are discussed.
PMCID: PMC2811488  PMID: 19772832
9.  Trapped in a vicious loop: Toll-like receptors sustain the spontaneous cytokine production by rheumatoid synovium 
Synovial tissue of patients with rheumatoid arthritis (RA) spontaneously produces several cytokines, of which a fundamental role in joint inflammation and destruction has been established. However, the factors sustaining this phenomenon remain poorly understood. In a recent report, blockade of Toll-like receptor 2 (TLR2) was found to inhibit the spontaneous release of inflammatory cytokines by intact RA synovial explant cultures. Adding to the recent evidence implicating other TLRs (in particular, TLR4), this observation highlights the potential of TLRs as therapeutic targets to suppress the local production of multiple cytokines and to control the chronic inflammatory loop in RA.
PMCID: PMC3132033  PMID: 21542897
10.  The Role of Cytokines in the Pathogenesis and Treatment of Systemic Lupus Erythematosus 
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by a defect in immune tolerance and exacerbated by both the innate and adaptive arms of the immune response. SLE-associated immune hyperactivity can be detected systemically as elevations in levels of cytokines along with their upregulated receptors expressed by hematopoietic cells. Importantly, increased levels of cytokines and their receptors can be observed in target organs, and it is clear that they have important roles in disease pathogenesis. Recent therapeutic strategies have focused on proximal cytokines, such as interferon-α, interleukin (IL)-1, IL-6, and tumor necrosis factor as a result of the efficacious use of biologic agents for intervention in rheumatoid arthritis and other autoimmune diseases. Despite the recent advances in understanding the cytokine networks involved in autoimmune diseases and more specifically in SLE, the diagnosis and prognosis of lupus remain a challenge. Lupus is heterogeneous and unpredictable; moreover, the frequency and severity of flares can be difficult to determine and treat. A better understanding of the regulation of expression of key cytokines and their receptors can likely provide important clues to the pathogenic mechanisms underlying specific forms of SLE, and pave the way toward more effective therapeutics.
PMCID: PMC3189549  PMID: 21787222
11.  Canadian Association of University Surgeons’ Annual Symposium. Surgical simulation: The solution to safe training or a promise unfulfilled? 
Canadian Journal of Surgery  2012;55(4 Suppl 2):S200-S206.
At its 2009 annual symposium, chaired by Dr. William (Bill) Pollett, the Canadian Association of University Surgeons brought together speakers with expertise in surgery and medical education to discuss the role of surgical simulation for improving surgical training and safety. Dr. Daniel Jones, of Harvard University and the 2009 Charles Tator Lecturer, highlighted how simulation has been used to teach advanced laparoscopic surgery. He also outlined how the American College of Surgeons is moving toward competency assessments as a requirement before surgeons are permitted to perform laparoscopic surgery on patients. Dr. Teodor Grantcharov, from the University of Toronto, highlighted the role of virtual reality simulators in laparoscopic surgery as well as box trainers. Dr. Peter Brindley from the University of Alberta, although a strong proponent of simulation, cautioned against an overzealous adoption without addressing its current limitations. He also emphasized simulation’s value in team training and crisis resource management training. Dr. Chris de Gara, also from the University of Alberta, questioned to what extent simulators should be used to determine competency. He raised concerns that if technical skills are learned in isolation, they may become “decontextualized,” and therefore simulation might become counterproductive. He outlined how oversimplification can have an “enchanting” effect, including a false sense of security. As a result, simulation must be used appropriately and along the entire education continuum. Furthermore, far more needs to be done to realize its role in surgical safety.
PMCID: PMC3432250  PMID: 22854147
12.  A Cytokine-Centric View of the Pathogenesis and Treatment of Autoimmune Arthritis 
Cytokines are immune mediators that play an important role in the pathogenesis of rheumatoid arthritis (RA), an autoimmune disease that targets the synovial joints. The cytokine environment in the peripheral lymphoid tissues and the target organ (the joint) has a strong influence on the outcome of the initial events that trigger autoimmune inflammation. In susceptible individuals, these events drive inflammation and tissue damage in the joints. However, in resistant individuals, the inflammatory events are controlled effectively with minimal or no overt signs of arthritis. Animal models of human RA have permitted comprehensive investigations into the role of cytokines in the initiation, progression, and recovery phases of autoimmune arthritis. The discovery of interleukin-17 (IL-17) and its association with inflammation and autoimmune pathology has reshaped our viewpoint regarding the pathogenesis of arthritis, which previously was based on a simplistic T helper 1 (Th1)-Th2 paradigm. This review discusses the role of the newer cytokines, particularly those associated with the IL-17/IL-23 axis in arthritis. Also presented herein is the emerging information on IL-32, IL-33, and IL-35. Ongoing studies examining the role of the newer cytokines in the disease process would improve understanding of RA as well as the development of novel cytokine inhibitors that might be more efficacious than the currently available options.
PMCID: PMC3234492  PMID: 22149412
13.  Th17 cytokines and arthritis 
Seminars in Immunopathology  2010;32(1):43-53.
Th17 cells are implicated in human autoimmune diseases, such as rheumatoid arthritis (RA), although it has not been established whether this persistent destructive arthritis is driven by Th1 and/or Th17 cells. Interleukin-17A (IL-17A) contributes to the pathogenesis of arthritis as has been shown in several experimental arthritis models. Importantly, recent data from first clinical trials with anti-IL-17A antibody treatment in psoriatic arthritis patients and RA patients looks promising. This review summarizes the findings about the role of Th17 cells in arthritis and discusses the impact of the different Th17 cytokines in the pathogenesis of this disease. However, further studies are needed to unravel the interplay between IL-17A and other Th17 cytokines such as IL-17F, IL-22, and IL-21 in the pathoimmunological process of this crippling disease, in particular, whether regulating Th17 cell activity or specific combinations of Th17 cytokines will have additional value compared to neutralizing IL-17A activity alone. Moreover, tumor necrosis factor-positive Th17 cells are discussed as potential dangerous cells in driving persistent arthritis in human early RA.
PMCID: PMC2836464  PMID: 20127485
Autoimmunity; Inflammation; T cells; IL-17A; IL-17F; IL-22
14.  30B. An Integrative Systems-biology Approach to Autoimmune Disease: Leaving the Era of Reaction and Entering the New Proactive Era of Prediction 
Focus Area: Integrative Approaches to Care
Autoimmune disease is growing at epidemic proportions, and standard interventions are based on symptom control and immune suppression. This presentation with review a proactive integrative systems biology approach to disease prediction, prevention, and treatment, including various evidence-based modalities. Presentation elements will include an exploration of the role of the GI microbiota, food immune reactions, stealth infections and molecular mimicry in autoimmune disease pathogenesis and how these may serve as leverage points for clinical interventions. The hygiene hypothesis and changes in early environmental antigen exposue also will be explored. New opportunities for proactive screening for at-risk subjects for autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel diseases, diabetes, multiple sclerosis, lupus, and others using emerging predictive antibody testing also will be reviewed and discussed. Integration of CAM providers with rheumatologists and other primary specialist also will be addressed.
PMCID: PMC3875089
15.  Potential new targets in arthritis therapy: interleukin (IL)‐17 and its relation to tumour necrosis factor and IL‐1 in experimental arthritis 
Annals of the Rheumatic Diseases  2006;65(Suppl 3):iii29-iii33.
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by chronic joint inflammation and destruction. Interleukin (IL)‐17 is a T cell cytokine expressed in the synovium and synovial fluid of patients with RA. IL‐17 is a potent inducer of various cytokines such as tumour necrosis factor (TNF) and IL‐1. IL‐17 has been shown to have additive or even synergistic effects with TNF and IL‐1 during the induction of cytokine expression and joint damage in vitro and in vivo. TNFα and IL‐1 are considered powerful targets in the treatment of RA because of their leading role in driving the enhanced production of cytokines, chemokines, and degradative enzymes. Besides anti‐TNF and anti‐IL‐1 therapies, whose clinical efficacy is now established, new targets have been proposed for RA which is not responding to conventional treatments. This paper discusses the role of IL‐17 in experimental arthritis and its interrelationship with TNF and IL‐1, currently the most targeted cytokines in the treatment of RA. IL‐17 is involved in both initiation and progression of murine experimental arthritis. Studies have shown that IL‐17 not only synergises with TNF, but also enhances inflammation and destruction independent of IL‐1 and TNF. On the basis of these studies, the authors propose IL‐17 as an interesting additional target in the treatment of RA.
PMCID: PMC1798387  PMID: 17038468
IL‐17; IL‐1; TNF; target; arthritis
16.  Platelets Amplify Inflammation in Arthritis via Collagen-Dependent Microparticle Production 
Science (New York, N.Y.)  2010;327(5965):580-583.
In addition to their pivotal role in thrombosis and wound repair, platelets participate in inflammatory responses. We investigated the role of platelets in the autoimmune disease rheumatoid arthritis. We identified platelet microparticles—submicrometer vesicles elaborated by activated platelets—in joint fluid from patients with rheumatoid arthritis and other forms of inflammatory arthritis, but not in joint fluid from patients with osteoarthritis. Platelet microparticles were proinflammatory, eliciting cytokine responses from synovial fibroblasts via interleukin-1. Consistent with these findings, depletion of platelets attenuated murine inflammatory arthritis. Using both pharmacologic and genetic approaches, we identified the collagen receptor glycoprotein VI as a key trigger for platelet microparticle generation in arthritis pathophysiology. Thus, these findings demonstrate a previously unappreciated role for platelets and their activation-induced microparticles in inflammatory joint diseases.
PMCID: PMC2927861  PMID: 20110505
17.  Anti-TNF-α Therapies in Systemic Lupus Erythematosus 
Tumor necrosis factor (TNF)-α is not just a proinflammatory cytokine. It has also been proposed to be an immunoregulatory molecule that can alter the balance of T regulatory cells. Anti-TNF-α therapies have been provided clinical benefit to many patients and introduced for treating moderate to severe rheumatoid arthritis, Crohn's disease, and other chronic inflammatory disorders. However, their use also is accompanied by new or aggravated forms of autoimmunity, such as formation of autoantibodies, including antinuclear antibodies (ANAs), antidouble-stranded DNA (dsDNA) antibodies, and anticardiolipin antibodies (ACL). Systemic lupus erythematosus (SLE) is a disease with autoimmune disturbance and inflammatory damage. The role of TNF-α in human SLE is controversial. Here we review the role of TNF-α in the pathophysiological processes of SLE and the likely effects of blocking TNF-α in treatment of SLE.
PMCID: PMC2896679  PMID: 20625488
18.  Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (Trail) Is an Inhibitor of Autoimmune Inflammation and Cell Cycle Progression 
The Journal of Experimental Medicine  2000;191(7):1095-1104.
The tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) induces apoptosis of tumor cells but not normal cells; its role in normal nontransformed tissues is unknown. We report here that chronic blockade of TRAIL in mice exacerbated autoimmune arthritis, and that intraarticular TRAIL gene transfer ameliorated the disease. In vivo, TRAIL blockade led to profound hyperproliferation of synovial cells and arthritogenic lymphocytes and heightened the production of cytokines and autoantibodies. In vitro, TRAIL inhibited DNA synthesis and prevented cell cycle progression of lymphocytes. Interestingly, TRAIL had no effect on apoptosis of inflammatory cells either in vivo or in vitro. Thus, unlike other members of the tumor necrosis factor superfamily, TRAIL is a prototype inhibitor protein that inhibits autoimmune inflammation by blocking cell cycle progression.
PMCID: PMC2193179  PMID: 10748228
autoimmunity; inflammation; apoptosis; cytokine; TRAIL
19.  Evidence that cytokines play a role in rheumatoid arthritis 
The Journal of Clinical Investigation  2008;118(11):3537-3545.
A large number of cytokines are active in the joints of patients with rheumatoid arthritis (RA). It is now clear that these cytokines play a fundamental role in the processes that cause inflammation, articular destruction, and the comorbidities associated with RA. Following the success of TNF-α blockade as a treatment for RA, other cytokines now offer alternative targets for therapeutic intervention or might be useful as predictive biomarkers of disease. In this Review, we discuss the biologic contribution and therapeutic potential of the major cytokine families to RA pathology, focusing on molecules contained within the TNF-α, IL-1, IL-6, IL-23, and IL-2 families.
PMCID: PMC2575731  PMID: 18982160
20.  The Role of T-Cell Leukemia Translocation-Associated Gene Protein in Human Tumorigenesis and Osteoclastogenesis 
Synovial tissues of patients with rheumatoid arthritis (RA) include factors regulating bone resorption, such as receptor activator NF-κB ligand (RANKL), TNF-α, IL-6, IL-17, and IFN-γ. However, in addition to these cytokines, other factors expressed in synovial tissues may play a role in regulating bone resorption. In 2009, we demonstrated that novel peptides from T-cell leukemia translocation-associated gene (TCTA) protein expressed in synovial tissues from patients with RA inhibit human osteoclastogenesis, preventing cellular fusion via the interaction between TCTA protein and a putative counterpart molecule. Only a few studies on the role of TCTA protein have been reported. Genomic Southern blots demonstrated a reduced TCTA signal in three of four small cell lung cancer cell lines, suggesting the loss of one of the two copies of the gene. In the current paper, we reviewed the roles of TCTA protein in lung cancer cell lines and human osteoclastogenesis.
PMCID: PMC3228289  PMID: 22174563
21.  Effector mechanisms of interleukin-17 in collagen-induced arthritis in the absence of interferon-γ and counteraction by interferon-γ 
Arthritis Research & Therapy  2009;11(4):R122.
Interleukin (IL)-17 is a pro-inflammatory cytokine in rheumatoid arthritis (RA) and collagen-induced arthritis (CIA). Since interferon (IFN)-γ inhibits Th17 cell development, IFN-γ receptor knockout (IFN-γR KO) mice develop CIA more readily. We took advantage of this model to analyse the mechanisms of action of IL-17 in arthritis. The role of IFN-γ on the effector mechanisms of IL-17 in an in vitro system was also investigated.
IFN-γR KO mice induced for CIA were treated with anti-IL-17 or control antibody. The collagen type II (CII)-specific humoral and cellular autoimmune responses, myelopoiesis, osteoclastogenesis, and systemic cytokine production were determined. Mouse embryo fibroblasts (MEF) were stimulated with IL-17, tumor necrosis factor (TNF)-α and the expression of cytokines and chemokines were determined.
A preventive anti-IL-17 antibody treatment inhibited CIA in IFNγR KO mice. In the joints of anti-IL-17-treated mice, neutrophil influx and bone destruction were absent. Treatment reduced the cellular autoimmune response as well as the splenic expansion of CD11b+ cells, and production of myelopoietic cytokines such as granulocyte macrophage colony-stimulating factor (GM-CSF) and IL-6. IL-17 and TNF-α synergistically induced granulocyte chemotactic protein-2 (GCP-2), IL-6 and receptor activator of NFκB ligand (RANKL) in MEF. This induction was profoundly inhibited by IFN-γ in a STAT-1 (signal transducer and activator of transcription-1)-dependent way.
In the absence of IFN-γ, IL-17 mediates its pro-inflammatory effects mainly through stimulatory effects on granulopoiesis, neutrophil infiltration and bone destruction. In vitro IFN-γ profoundly inhibits the effector function of IL-17. Thus, aside from the well-known inhibition of the development of Th17 cells by IFN-γ, this may be an additional mechanism through which IFN-γ attenuates autoimmune diseases.
PMCID: PMC2745806  PMID: 19686583
22.  SYNAPSE, Symposium for Young Neuroscientists and Professors of the Southeast: A One-day, Regional Neuroscience Meeting Focusing on Undergraduate Research 
The Symposium for Young Neuroscientists and Professors of the Southeast (SYNAPSE; was designed to encourage contacts among faculty and students interested in neuroscience. Since its inception in 2003, the SYNAPSE conference has consistently drawn faculty and undergraduate interest from the region. This unique meeting provides undergraduates with a valuable opportunity for neuroscience education; students interact with noted neuroscience faculty, present research results, obtain feedback from neuroscientists at other institutions, and form connections with other neuroscientists in the region. Additionally, SYNAPSE allows undergraduate students and faculty to attend workshops and panel discussions about issues related to professional skills and career options. The SYNAPSE conference currently travels among host institutions in the southeastern United States in two-year cycles. This article briefly describes the genesis of SYNAPSE and reviews SYNAPSE conferences from 2006 through 2010. The goal of this paper is to highlight key issues organizers have experienced launching, sustaining, and hosting this regional undergraduate neuroscience conference as well as assist faculty to develop similar conferences.
PMCID: PMC3592723  PMID: 23493950
undergraduate education; neuroscience; conferences
23.  B Cell in Autoimmune Diseases 
Scientifica  2012;2012:215308.
The role of B cells in autoimmune diseases involves different cellular functions, including the well-established secretion of autoantibodies, autoantigen presentation and ensuing reciprocal interactions with T cells, secretion of inflammatory cytokines, and the generation of ectopic germinal centers. Through these mechanisms B cells are involved both in autoimmune diseases that are traditionally viewed as antibody mediated and also in autoimmune diseases that are commonly classified as T cell mediated. This new understanding of the role of B cells opened up novel therapeutic options for the treatment of autoimmune diseases. This paper includes an overview of the different functions of B cells in autoimmunity; the involvement of B cells in systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes; and current B-cell-based therapeutic treatments. We conclude with a discussion of novel therapies aimed at the selective targeting of pathogenic B cells.
PMCID: PMC3692299  PMID: 23807906
24.  B Cells in Autoimmune Diseases 
Scientifica  2012;2012:215308.
The role of B cells in autoimmune diseases involves different cellular functions, including the well-established secretion of autoantibodies, autoantigen presentation and ensuing reciprocal interactions with T cells, secretion of inflammatory cytokines, and the generation of ectopic germinal centers. Through these mechanisms B cells are involved both in autoimmune diseases that are traditionally viewed as antibody mediated and also in autoimmune diseases that are commonly classified as T cell mediated. This new understanding of the role of B cells opened up novel therapeutic options for the treatment of autoimmune diseases. This paper includes an overview of the different functions of B cells in autoimmunity; the involvement of B cells in systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes; and current B-cell-based therapeutic treatments. We conclude with a discussion of novel therapies aimed at the selective targeting of pathogenic B cells.
PMCID: PMC3692299  PMID: 23807906
25.  Target effector role of vascular endothelium in the inflammatory response: insights from the clinical trial of anti-TNF alpha antibody in rheumatoid arthritis. 
Molecular Pathology  1997;50(5):225-233.
Rheumatoid arthritis (RA) is characterised by chronic joint inflammation and infiltration by cells from the blood, especially activated T cells and macrophages, together with formation of new blood vessels. The overgrowth of the synovial lesion results eventually in destruction of cartilage and bone. Cytokines play a major role in RA, both in systemic inflammatory processes, such as induction of acute phase protein synthesis, and in the stimulation of new blood vessel development and recruitment of leucocytes to developing lesions. The focus for the interplay of many cytokines is the endothelium, the lining layer of the vasculature. This is the primary target for circulating mediators, and it controls the traffic of cells and molecules from the bloodstream into underlying tissues. Targeting the action of individual cytokines--for example, using antibody against tumour necrosis factor alpha (TNF alpha), has been shown to be very effective in the treatment of RA. Blockade of TNF alpha activity results in deactivation of the endothelium, manifested as reduced expression of adhesion molecules and chemoattractant cytokines, leading to diminished trafficking of inflammatory cells to synovial joints. In addition anti-TNF alpha decreases circulating levels of the potent angiogenic cytokine VEGF, suggesting that new blood vessel formation, and hence the supply of nutrients to the growing synovial lesion, is also affected. These observations lend further support to the hypothesis that interruption of a component of the cytokine network in RA may modulate disease progression, and point the way towards the development of new therapeutic strategies for the treatment of chronic inflammatory disease states.
PMCID: PMC379637  PMID: 9497911

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