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ID PMID Title PublicationDate abstract
19355917 The critical role of Toll-like receptor signaling pathways in the induction and progressio 2009 Apr Toll-like receptors (TLRs) form a large family of pattern recognition receptors with at least 11 members in human and 13 in mouse. TLRs recognize a wide variety of microbial components and potential host-derived agonists that have emerged as key mediators of innate immunity. TLR signaling also plays an important role in the activation of the adaptive immune system by inducing proinflammatory cytokines and upregulating costimulatory molecules of antigen presenting cells. The dysregulation of TLR signaling may cause autoimmunity. This review discusses the contribution of TLR signaling to the initiation and progression of autoimmune diseases, such as rheumatoid arthritis, experimental autoimmune encephalitis, myocarditis, hepatitis, kidney disease, systemic lupus erythematosus, diabetes, obesity, and experimental autoimmune uveitis as well as aging. The involvement of TLR signaling in the pathogenesis of autoimmune diseases may provide novel targets for the development of therapeutics.
19229504 [Drug-induced lupus erythematosus tumidus during treatment with adalimumab]. 2009 Oct Patients treated with TNF-alpha inhibitors frequently have serum autoantibodies, but only a few develop clinically apparent lupus erythematosus. The TNF-alpha inhibitor adalimumab is a fully humanized antibody and seems to induce autoantibodies less frequently than other drugs of this group. We report on a patient with rheumatoid arthritis, who developed anti-histone antibodies and lupus tumidus after eight months on adalimumab therapy.
19182731 Labeling monocytes for imaging chronic inflammation. 2009 Feb With growing interest in cell-based scintigraphic diagnosis or therapy monitoring, there is an increasing demand for non-invasive observation and quantification of cell trafficking in the preclinical and clinical setting. Monocytes are members of the human mononuclear phagocyte system originating from a myeloid precursor in the bone. Labeled monocytes are being used for investigation of pathogenesis like atherosclerosis and for monitoring of therapeutic intervention in inflammatory diseases like rheumatoid arthritis. Labeling mononuclear cells at high specific activity without affecting their biological functions allows (delayed) non-invasive imaging with g or PET cameras. Monocytes labeled before their final differentiation into macrophages or dendritic cells may reveal centers of inflammation in a patient and, thereby, contribute to scintigraphic diagnosis. Macrophages or dendritic cells may be in vitro cultured and by means of genetic transformation specified towards specific targets prior to re-injection, an approach with therapeutic potency. This review addresses issues on autologous monocytes, particularly their properties and labeling for non-invasive in vivo radionuclide imaging of chronic inflammation.
21060670 A retrospective study of nine cases of Acanthamoeba keratitis. 2010 Oct 21 PURPOSE: To evaluate the clinical features of Acanthamoeba keratitis in nine patients diagnosed at Dokkyo Medical University Koshigaya Hospital, Saitama, Japan. METHODS: In nine eyes of nine patients, Acanthamoeba keratitis was diagnosed by direct light microscopy of corneal scrapings stained by the Parker ink-potassium hydroxide method between September 2006 and September 2009. Their clinical features and course were studied retrospectively. Antifungal eye drops, systemic antifungal therapy, and surgical debridement of the corneal lesions were performed in all patients. RESULTS: At presentation, the clinical stage was initial in six cases, transient in one case, and complete in two cases. The patients were all contact lens wearers who had washed their lens storage cases with tap water. After treatment, final visual acuity was improved in six cases, unchanged in one case, and worse in two cases. The patient with the worst final vision (hand motion) had rheumatoid arthritis and was taking oral prednisolone, which led to corneal perforation and prevented adequate debridement from being done. CONCLUSION: Acanthamoeba keratitis is closely related to wearing contact lenses and washing the lens storage case with tap water. Although final visual acuity improved after treatment in most patients, insufficient surgical debridement resulted in a poor visual prognosis.
20803989 [A case of hypertrophic pachymeningitis impeding differential diagnosis of mycosis of orbi 2010 Aug PURPOSE: Mycosis of the orbital apex is often fatal. We report case of orbital apex syndrome, which appeared to have been caused by hypertrophic pachymeningitis with positive systemic mycosis antigens treated with systemic corticosteroid combined with antimicrobiotic therapy. CASE: A 57-year-old woman presented with disturbed ocular motility and visual disturbance of her left eye. She had rheumatoid arthritis. Magnetic resonance imaging(MRI) showed an abnormal blush in the left orbital apex and meningeal thickening in the cranial base, leading to the diagnosis of hypertrophic pachymeningitis. She also had candidemia. Systemic corticosteroids combined with antimicrobiotic therapy resulted in improved clinical ocular manifestations. She died 13 months later due to interstitial pneumonia. CONCLUSION: The diagnosis of this case was difficult because of the candidemia. But the effective steroid response indicates that the probable cause was hypertrophic pachymeningitis due to RA. To avoid complications, hypertrophic pachymeningitis associated with fungemia should be treated with corticosteroids combined with antimicrobiotic therapy.
20549288 Generalized laxity of connective tissue as a possible syndrome in systemic lupus erythemat 2010 Oct We report a case of systemic lupus erythematosus (SLE) with Jaccoud's arthropathy, presenting atlantoaxial subluxation and multiple joint hypermobility. Radiological studies showed degenerative changes, but no destructive changes like rheumatoid arthritis (RA) were observed. Since these are rare complications of SLE, the coexistence of these complications suggests that they have a common pathogenesis. Generalized laxity of connective tissues may be a novel syndrome in SLE.
20399786 The role of TNF in parasitic diseases: still more questions than answers. 2010 Jul The inhibition of TNF with therapeutic monoclonal antibodies or antibody/receptor fusion proteins in rheumatoid arthritis still constitutes the benchmark for a successful intervention in an ongoing auto-immune-inflammatory disease and underlines the importance of this cytokine. TNF plays a central role in the defence against intracellular infections and is responsible for the promotion of different aspects of the innate immune response such as inflammatory cell recruitment and cell differentiation. While this cytokine generally displays pro-inflammatory activities supporting the early stages of the inflammatory response, it has been demonstrated to be especially important during infection with intracellular pathogens and, consequently, leishmaniasis of TNF(-/-) mice ends fatally. However, the specific activities of TNF that confer protection are not yet fully understood. This review will summarize the current understanding of TNF function and signalling, and will discuss recent work in the models of malaria, toxoplasmosis, trypanosomiasis and leishmaniasis with particular emphasis on work with gene-deficient mouse models.
20377061 [Acute bilateral lesion of the patellar tendon associated to diabetes mellitus. Case repor 2010 Jan The bilateral patellar tendon tear is very infrequent. Various pathological conditions may affect the extensor mechanism including kidney disease, diabetes mellitus, hyperparathyroidism, rheumatoid arthritis, systemic lupus erythematosus, osteomalacia, infection, obesity, corticosteroid therapy and even osteogenesis imperfect. We present the case of a 43-year-old male with a history of type-2 diabetes mellitus, systemic hypertension and exogenous obesity, who sustained a bilateral patellar tendon tear. He received surgical and medical treatment and was followed-up for one year, with satisfactory functional outcomes.
20364159 microRNAs: critical regulators in Th17 cells and players in diseases. 2010 May microRNAs are a novel group of small, conserved, non-coding RNA molecules that are present in all species. These molecules post-transcriptionally regulate gene expression by targeting mRNAs for degradation or by repressing the translation of the mRNAs. A good understanding of miRNA-mediated gene regulation is critical to gain a comprehensive view of many physiological processes and disease states. Emerging evidence demonstrates that miRNAs play an important role in the differentiation and function of the adaptive immune system. This review provides an overview of the diverse functions of miRNAs in modulating immune responses and in immune cell development, particularly the development of Th17 cells, and explores the involvement of miRNAs in several autoimmune diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and diabetes.
20298124 Type I interferons in systemic autoimmunity. 2010 Apr Type I IFN (IFN-I) was firstly described in 1957 as a soluble factor responsible for viral resistance in vitro. Today, it is well known that the IFN-I family comprises a wide number of cytokines with different modulatory effects on angiogenesis, cell growth, fibrosis, and apoptosis. However, one of the most important functions of IFN-I is the capability to trigger a complex array of cellular responses that result in a host-protective antiviral response. For this reason, IFN-I can be considered a "director" of protective immune responses. The recent finding of the so-called interferon signature in patients suffering from different autoimmune diseases has underlined its possible role in the pathogenesis of these diseases. On the other hand, IFN-alpha/beta is reported to be efficacious in the treatment of some autoimmune and infectious diseases not responsive to conventional therapy. On these occasions, the treated patients often start or increase autoantibody production supporting the role of IFN as inducer of an autoimmune response. In this review, we will underline recent acquisitions about IFN-I biology, with a focus on the relevance of the induction of some autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, dermato/polymiositis, and Sjogren's syndrome.
20192155 Chronic closed talus dislocation: a rare presentation and treatment dilemma. 2010 Feb A chronic presentation of closed dorsolateral dislocation of the talus is a rare injury. A 35-year-old woman presented with pain and deformity of the right foot of 6 months' duration. Her medical history was significant for rheumatoid arthritis, for which she was being treated with steroids. Radiographs and computed tomography of the right foot showed dorsolateral talar dislocation with fracture of the medial malleolus. Dislocation of the talus from the tibiotalar, talocalcaneal, and talonavicular joints was indicative of talus dislocation with a fracture of the medial malleolus rather than a fracture-dislocation of the ankle joint. Because of chronic presentation of the injury and an inability to reduce this talus dislocation by closed methods, open total talectomy was performed. At 2-year follow-up, the patient had an AOFAS score of 78. The patient had an obvious limp on the affected limb but managed her activities of daily living well without a shoe raise or brace. Because of the severe varus inversion deformity of the foot preoperatively, the patient was not able to walk. Postoperatively, the deformity was corrected and the patient was able to stand and walk; she was satisfied with the outcome of the surgery.To our knowledge, this is the first report of chronic closed dorsolateral talus dislocation. We recommend that chronic closed isolated dorsolateral talus dislocation can be effectively managed by total talectomy.
20047032 Protein pharmaceuticals: discovery and preclinical development. 2009 Proteins are natural molecules that carry out important cellular functions within our bodies. Their precise role is crucial to the maintenance of good health. Malfunctioning proteins or those not produced optimally result in disease. The foundation of biopharmaceutical drug therapy has therefore been to modulate cellular function by targeting specific proteins expressed on or outside the cell. Because most biopharmaceuticals are natural in origin, they are biologically and chemically very different from conventional medicines. In addition to differences in mechanism of action, biopharmaceuticals differ in the process by which they get manufactured and delivered. Because of their large, complex structure, they must often be produced by culturing cells and then purified from a host of cellular components. This can be time-consuming and costly. Also, most biopharmaceuticals are given by injection under the skin or by infusion into the veins. This creates significant limitations to their utility. Nonetheless, biopharmaceuticals can be very powerful and selective in disease applications such as in rheumatoid arthritis or cancer. This chapter describes methods by which proteins drugs are discovered, optimized and developed. It also covers novel agents and next generation proteins as well as some of the challenges and opportunities in the area.
19811308 The 12/15-lipoxygenase pathway promotes osteoclast development and differentiation. 2009 May Although 12/15-lipoxygenase (12/15-LO) has been implicated as negative regulator of systemic bone mass in mice and humans, the underlying mechanisms remain elusive. Here, we show that 12/15-LO is a positive regulator of osteoclast (OC) development. Enzymatic inhibition as well as genetic ablation of 12/15-LO significantly impaired osteoclastogenesis. Conversely, addition of the 12/15-LO-derived eicosanoids 12- and 15-HETE augmented differentiation of precursors into fully matured OCs. Together these data point towards a crucial role of 12/15-LO in the regulation of OC development. Therefore, 12/15-LO and its human homologue 15-LO may display novel targets for the treatment of diseases such as osteoporosis and rheumatoid arthritis.
19663701 Rat monoclonal antibodies specific for LST1 proteins. 2009 Aug The LST1 gene is located in the human MHC class III region and encodes transmembrane and soluble isoforms that have been suggested to play a role in the regulation of the immune response and are associated with inflammatory diseases such as rheumatoid arthritis. Here we describe the generation and characterization of the first monoclonal antibodies against LST1. Two hybridoma lines secreting monoclonal antibodies designated 7E2 and 8D12 were established. The 7E2 antibody detects recombinant and endogenous LST1 by Western blot analysis while 8D12 reacts with recombinant and endogenous LST1 in immunoprecipitation and flow cytometry procedures. The newly established antibodies were used to survey LST1 protein expression in human cell lines, which was found to be tightly regulated, allowing the expression of transmembrane isoforms but suppressing soluble isoforms.
19577332 Palisaded neutrophilic granulomatous dermatitis associated with systemic lupus erythematos 2009 Oct Palisaded neutrophilic granulomatous dermatitis is a rare but increasingly recognized cutaneous manifestation of connective tissue disorders. It is reported most commonly with rheumatoid arthritis but also occasionally in association with systemic lupus erythematosus, inflammatory bowel disease, lymphoproliferative disorders, and systemic vasculitides. The clinicopathological presentation is highly variable, which has led to suggestions that it encompasses a number of distinct diseases. Most previous cases have reported only a single clinical and histologic manifestation of the condition within an individual. Here, we present a case of systemic lupus erythematosus-associated palisaded neutrophilic granulomatous dermatitis in which a striking evolution of both clinical and histologic features was observed during the course of 7 years, providing compelling evidence for the proposal that palisaded neutrophilic granulomatous dermatitis represents a disease spectrum rather than separate disease entities.
21665121 How to measure the impact of musculoskeletal conditions. 2010 Dec Musculoskeletal conditions are universally prevalent among all age and gender groups, across all socio-demographic strata of society. Their impact is pervasive yet this is not widely recognised at the level of health policy and priority. Musculoskeletal conditions are a diverse group of disorders with regard to pathophysiology but are linked anatomically and by their association with pain and impaired physical function; encompassing a spectrum of conditions, including inflammatory diseases such as rheumatoid arthritis or gout; age-related conditions such as osteoporosis and osteoarthritis; common conditions of unclear aetiology such as back pain and fibromyalgia; and those related to activity or injuries such as occupational musculoskeletal disorders, sports injuries or the consequences of falls and major trauma. The increasing number of older people and the changes in lifestyle throughout the world with increasing obesity and reduced physical activity mean that the burden on people and society will increase dramatically. The growing awareness of the burden increases the need for accurate measurement and assessment of the burden as well as measurement of the impact of any public health action. This chapter considers theoretical and practical issues relevant to measuring the buden of musculoskeltal conditions in populations, societies and individuals.
21409915 Pattern of joints involvement in Kashin-Beck disease: a local osteochondropathy in China. 2010 Jan BACKGROUND: Kashin-Beck Disease (KBD) is an endemic osteochondropathy. The disease starts in childhood and attacks the growth of joint cartilage, the joints become deformed and painful, and the worst forms result in dwarfism. The most fiequent joints involved are the finger, wrist, ankles, knees and elbows. In this study the pattern of joints involved in KBD was studied. METHODS: A total of 368 patients aged above 13 from 6 villages in endemic areas of the Shaanxi province, located in the northwest of China, were selected through multistage stratified sampling. The patients were diagnosed based on the clinical criteria for diagnosis of KBD. The patients were administered with a battery of questionnaires along with clinical examination for joint involvement. RESULTS: The patients presented both as oligoarticular as well as polyarticular pattern. Smaller joints were more frequently involved with a proximal-distal pattern. The number of joints involved increased with the severity of the disease. CONCLUSION: Proximal smaller joints are more frequently involved in the disease. The involvement of bigger joints takes place in later stages of disease, i.e., in the second and third degree. The pattern of joint involvement shows some correlation with Rheumatoid Arthritis which needs further investigation and comparative studies.
19379173 A case report of successful treatment with plasma exchange for hemophagocytic syndrome ass 2009 Feb An infantile case of hemophagocytic syndrome (HPS) with systemic juvenile idiopathic arthritis (s-JIA), refractory to methylprednisolone pulse therapy and cyclosporine A administration, was successfully treated by plasma exchange. The patient was a one-year-old Japanese girl who had developed recurrent steroid-dependent signs, including fever, skin eruption, and hepatopathy, while in France, where she had been diagnosed as having s-JIA at eight months of age. As a high fever and rheumatoid rash were evident on arrival at our hospital, she was admitted and given intravenous methylprednisolone pulse therapy and cyclosporine A. She developed pancytopenia with a generalized clonic seizure, high fever, and liver dysfunction after her cytomegalovirus (CMV) titer became positive during the course of treatment; therefore, she was treated with ganciclovir. She was subsequently diagnosed as having HPS complicating s-JIA from the findings of a bone marrow aspirate. At this time, her blood examination data including a high level of C-reactive protein and hyperferritinemia, suggested that her s-JIA was very active, and the pancytopenia continued after her CMV titer became negative. Therefore, CMV infection against a background of active s-JIA could have triggered the HPS in this case. Because the HPS was resistant to an immunosuppressive regime of methylprednisolone pulse therapy and cyclosporine A, plasma exchange therapy was started. After three sessions of this therapy, the patient's symptoms and laboratory data were markedly improved. Our experience suggests that plasma exchange should be considered as a therapeutic tool for HPS refractory to conventional therapy.
21487477 The SCHOOL of nature: III. From mechanistic understanding to novel therapies. 2010 Jul Protein-protein interactions play a central role in biological processes and thus represent an appealing target for innovative drug design and development. They can be targeted by small molecule inhibitors, modulatory peptides and peptidomimetics, which represent a superior alternative to protein therapeutics that carry many disadvantages. Considering that transmembrane signal transduction is an attractive process to therapeutically control multiple diseases, it is fundamentally and clinically important to mechanistically understand how signal transduction occurs. Uncovering specific protein-protein interactions critical for signal transduction, a general platform for receptor-mediated signaling, the signaling chain homooligomerization (SCHOOL) platform, suggests these interactions as universal therapeutic targets. Within the platform, the general principles of signaling are similar for a variety of functionally unrelated receptors. This suggests that global therapeutic strategies targeting key protein-protein interactions involved in receptor triggering and transmembrane signal transduction may be used to treat a diverse set of diseases. This also assumes that clinical knowledge and therapeutic strategies can be transferred between seemingly disparate disorders, such as T cell-mediated skin diseases and platelet disorders or combined to develop novel pharmacological approaches. Intriguingly, human viruses use the SCHOOL-like strategies to modulate and/or escape the host immune response. These viral mechanisms are highly optimized over the millennia, and the lessons learned from viral pathogenesis can be used practically for rational drug design. Proof of the SCHOOL concept in the development of novel therapies for atopic dermatitis, rheumatoid arthritis, cancer, platelet disorders and other multiple indications with unmet needs opens new horizons in therapeutics.
21113195 Role of vitamin D in immune responses and autoimmune diseases, with emphasis on its role i 2010 Dec Vitamin D is a seco-steroid involved in calcium and phosphorus metabolism, and bone formation and mineralization, through binding to a specific nuclear receptor, vitamin D receptor (VDR). Besides its well-established functions on bone health, multiple lines of evidence have indicated the immunomodulatory roles of vitamin D. Vitamin D can affect both innate and adaptive immunity, and prevent autoimmune responses efficiently. Vitamin D regulates the immune responses by suppressing T cell proliferation and modulating macrophage functions. Epidemiological studies have shown that vitamin D deficiency is associated with multiple diseases such as rickets and cancer. Moreover, associations between vitamin D and autoimmune diseases have been confirmed in multiple sclerosis (MS), rheumatoid arthritis (RA), etc. The present review mainly summarized the recent findings on the immunomodulatory role of vitamin D in various disorders, with special focus on its role in MS, an autoimmune disease of the nervous system.