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ID PMID Title PublicationDate abstract
23304064 The pivotal role of TBK1 in inflammatory responses mediated by macrophages. 2012 Inflammation is a complex biological response of tissues to harmful stimuli such as pathogens, cell damage, or irritants. Inflammation is considered to be a major cause of most chronic diseases, especially in more than 100 types of inflammatory diseases which include Alzheimer's disease, rheumatoid arthritis, asthma, atherosclerosis, Crohn's disease, colitis, dermatitis, hepatitis, and Parkinson's disease. Recently, an increasing number of studies have focused on inflammatory diseases. TBK1 is a serine/threonine-protein kinase which regulates antiviral defense, host-virus interaction, and immunity. It is ubiquitously expressed in mouse stomach, colon, thymus, and liver. Interestingly, high levels of active TBK1 have also been found to be associated with inflammatory diseases, indicating that TBK1 is closely related to inflammatory responses. Even though relatively few studies have addressed the functional roles of TBK1 relating to inflammation, this paper discusses some recent findings that support the critical role of TBK1 in inflammatory diseases and underlie the necessity of trials to develop useful remedies or therapeutics that target TBK1 for the treatment of inflammatory diseases.
23246567 Detection and isolation of human serum autoantibodies that recognize oxidatively modified 2013 Apr The breakdown of human immune tolerance to self-proteins occurs by a number of mechanisms, including posttranslational modifications of host molecules by reactive oxygen, nitrogen, or chlorine species. This has led to great interest in detecting serum autoantibodies raised against small quantities of oxidatively modified host proteins in patients with autoimmune inflammatory diseases, such as rheumatoid arthritis. Here, we provide protocols for the preparation and chemical characterization of oxidatively modified protein antigens and procedures for their use in immunoblotting and ELISAs that detect autoantibodies against these antigens in clinical samples. These gel electrophoresis- and plate reader-based immunochemical methods sometimes suffer from low analytical specificity and/or sensitivity when used for serum autoantibody detection. This is often because a single solid-phase protein (antigen) is exposed to a complex mixture of serum proteins that undergo nonspecific binding. Therefore more sensitive/specific techniques are required to detect autoantibodies specifically directed against oxidatively modified proteins. To address this, we describe novel affinity chromatography protocols by which purified autoantibodies are isolated from small volumes (<1 ml) of serum. We have also developed strategies to conjugate submilligram amounts of isolated immunoglobulins and other proteins to fluorophores. This set of methods will help facilitate the discovery of novel diagnostic autoantibodies in patients.
23237509 Immune functions of serum amyloid A. 2012 Serum amyloid A (SAA) is a highly conserved, acute-phase protein synthesized predominantly by the liver. After secretion into the circulation, it associates with high-density lipoprotein (HDL) particles. During acute inflammation, serum SAA levels may rise up to 1000-fold, and under these conditions, SAA displaces apolipoprotein A-I from HDL, thus becoming the major apolipoprotein of circulating HDL3. SAA exhibits significant immunological activity by, for example, inducing the synthesis of several cytokines and by being chemotactic for neutrophils and mast cells. It exerts many of its immunological activities by binding and activating cell-surface receptors, including Toll-like receptor (TLR) 2 and TLR4, formyl peptide receptor-like 1 (FPRL1), class B scavenger receptor CD36, and the ATP receptor P2X7. SAA also recently has been shown to activate the inflammasome cascade, which has a key role in immune activation, thus further stressing the unique role of SAA in immunomodulation. Traditionally, SAA has been considered to have a key role in the pathogenesis of amyloid A-type amyloidosis, but we now understand that it may also participate in the pathogenesis of chronic inflammatory diseases, such as rheumatoid arthritis and atherosclerosis. Thus, SAA is one potential target in the treatment of diseases associated with chronic inflammation. The purpose of this review is to shed light on SAA as an immunologically active protein. We also focus on the recent findings implicating SAA in the regulation of the inflammasome cascade.
23133914 [Idiopathic eosinophilic pleural effusion--case report]. 2012 Jul Eosinophilic pleural effusion (EPE) is defined as exudative effusion that contains at least 10% eosinophils. The most common conditions associated with EPE are malignancy, infections, post-traumatic and post-surgical conditions, hypersensitivity, systemic autoimmune diseases, congestive heart failure, cirrhosis, pulmonary embolus, asbestosis and drug induced EPE. Pleural effusion accompanying autoimmune diseases is most common in patients with systemic lupus erythematosus, rheumatoid arthritis, howewer it rarely occurs in patients with progressive systemic sclerosis and polymiositis. EPE has rarely been reported in association with Churg Strauss syndrome. In about 14-25% of patients EPE can be defined as idiopathic when diagnostic procedures failed to identify the etiology. Treatment of EPE is based on the treatment of primary disease and with idiopathic form a good answer is reached using glucocorticoids. In this case report we presented the patient with idiopathic eosinophilic pleural effusion where in diagnostic procedures we excluded other diseases or conditions in which EPE can be shown, and with applied therapy with methylprednisolone we achieved excellent clinical response and final healing.
22842659 Genetic correlates of medical comorbidity associated with schizophrenia and treatment with 2012 Sep PURPOSE OF REVIEW: High comorbidity rates for various medical conditions have been documented in schizophrenia, being explained by factors either inherent to the disease or associated with antipsychotic treatment. The aim of this study is to review the genetic factors contributing to medical comorbidity in schizophrenia. RECENT FINDINGS: Based on clinical genetic studies in schizophrenia, comorbid impaired glucose tolerance/type 2 diabetes mellitus, most autoimmune disorders and cardiac autonomic dysregulation have the strongest evidence for familial predisposition. Similarly, of antipsychotic-induced adverse drug reactions, tardive dyskinesia, neuroleptic malignant syndrome, and antipsychotic-induced weight gain have some evidence for familial clustering. On the molecular genetic level, schizophrenia seems to share specific genes with type 2 diabetes mellitus and with autoimmune disorders. Various genes have been proposed to account for the reduced incidence of rheumatoid arthritis and cancer in schizophrenic patients and their relatives. Many pharmacogenetic association studies have pinpointed numerous, though often contradictory or poorly replicated, genes of modest effect size for tardive dyskinesia, neuroleptic malignant syndrome, clozapine-induced agranulocytosis, hyperprolactinaemia, antipsychotic-induced weight gain, and antipsychotic-induced QT prolongation. SUMMARY: Unravelling the genetic underpinnings of medical comorbidity associated with schizophrenia and its treatment is expected to highlight new pathogenetic pathways in both schizophrenia and comorbid medical conditions, and introduce personalized treatment strategies for schizophrenia patients.
22624966 Infectious and noninfectious aortitis: cross-sectional imaging findings. 2012 Jun "Aortitis" is a pathologic term that refers to an abnormal inflammation of the aortic wall. A wide spectrum of infectious, inflammatory, and idiopathic conditions may result in the development of aortitis. Infectious aortitis may be secondary to bacterial, tubercular, syphilitic, and viral pathogens. Although Takayasu arteritis and giant cell arteritis are the most common rheumatologic causes of aortitis, the other systemic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Behçet disease, and Cogan syndrome, may also be associated with aortitis. In addition, aortitis may also occur without any systemic diseases or infectious causes (idiopathic). Clinical features of aortitis are nonspecific and may include fever, abdominal or chest pain, and vascular insufficiency. Patients may have elevated serum levels of acute phase reactants. A high index of clinical suspicion is always needed for the diagnosis of aortitis in a timely manner. Cross-sectional imaging techniques, such as computed tomographic angiography, magnetic resonance imaging, magnetic resonance angiography, and positron emission tomography, are extremely helpful in diagnosis, assessing disease activity, treatment planning, and post-treatment follow-up. Many of the patients with aortitis may require a multimodality imaging approach for appropriate diagnosis. Knowledge of the clinical features and cross-sectional imaging findings of different types of aortitis permit optimal patient management.
22591655 Cardiovascular Risk and Psoriasis: the Role of Biologic Therapy. 2012 Dec One of the most clinically important aspects of recent advances in our understanding of psoriasis has been the detection of an association between this disease and an increased prevalence of cardiovascular risk factors. This increase in prevalence is, in turn, linked to a greater risk of morbidity and mortality related to acute myocardial infarction, cerebrovascular accident, and peripheral arterial disease. The chronic systemic inflammation present in psoriasis could explain why moderate to severe psoriasis is an independent risk factor for cardiovascular disease. The introduction of biologic therapies has greatly improved the expectations of treatment as well as the long-term control of psoriasis, and there is epidemiological evidence that these therapies may lower cardiovascular risk in psoriasis as they do in rheumatoid arthritis. Caution should, however, be exercised when prescribing biologic drugs in this setting, because adverse effects have been reported in association with the use of tumor necrosis factor inhibitors in patients with advanced congestive heart failure. Furthermore, a numerical imbalance (without statistical significance) between the groups receiving the biologic drug and the placebo groups was recently observed in the incidence of major cardiovascular events (nonfatal myocardial infarction and cerebrovascular accident and cardiovascular death) during the controlled periods of clinical trials of briakinumab and ustekinumab, 2 monoclonal antibodies that target the p40 subunit shared by IL 12 and IL-23. We review the current scientific evidence on this topic.
22566892 T cell-mediated modulation of mast cell function: heterotypic adhesion-induced stimulatory 2012 Close physical proximity between mast cells and T cells has been demonstrated in several T cell mediated inflammatory processes such as rheumatoid arthritis and sarcoidosis. However, the way by which mast cells are activated in these T cell-mediated immune responses has not been fully elucidated. We have identified and characterized a novel mast cell activation pathway initiated by physical contact with activated T cells, and showed that this pathway is associated with degranulation and cytokine release. The signaling events associated with this pathway of mast cell activation have also been elucidated confirming the activation of the Ras mitogen-activated protein kinase systems. More recently, we hypothesized and demonstrated that mast cells may also be activated by microparticles released from activated T cells that are considered as miniature version of a cell. By extension, microparticles might affect the activity of mast cells, which are usually not in direct contact with T cells at the inflammatory site. Recent works have also focused on the effects of regulatory T cells (Treg) on mast cells. These reports highlighted the importance of the cytokines IL-2 and IL-9, produced by mast cells and T cells, respectively, in obtaining optimal immune suppression. Finally, physical contact, associated by OX40-OX40L engagement has been found to underlie the down-regulatory effects exerted by Treg on mast cell function.
22519456 Hematopoietic stem cell transplantation for curing children with severe autoimmune disease 2012 Aug The cure of children with severe AD, especially patients with severe, progressive, and therapy-resistant autoimmunity, represents a challenge for current medical practice. The idea of HSCT as a promising therapeutic opportunity was borne accidentally from finding patients who, after undergoing HSCT for a hematological indication, were cured of a concomitant AD. Thus, over the last two decades, HSCT has been extensively investigated, and it has become an appealing therapy for rheumatological (juvenile rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis) and hematological diseases (immune cytopenias). Recently, interesting results have been also described in type 1 diabetes mellitus and Crohn's disease. Although the use of HSCT has been steadily rising in the last few years, many questions are still open, especially after the discoveries of many new biological agents. Given the low incidence of ADs in children, most of the data about the use of the HSCT for these diseases are taken from a mixed cohort of adults and children. The aim of this review is to summarize the published studies and to try to answer the question as to whether this procedure can be considered a promising approach.
22425228 The human IL-7 receptor gene: deletions, polymorphisms and mutations. 2012 Jun Most T cell subsets depend on IL-7 for survival. IL-7 binds to IL-7Rα and γc, initiating the signaling cascade. Deletion of IL-7Ra in humans has, for some time, been known to cause severe combined immunodeficiency. More recently, polymorphisms in IL-7R have been shown be a risk factor for a number of diseases that are autoimmune or involve excess immune and inflammatory responses including multiple sclerosis, type 1 diabetes, rheumatoid arthritis, primary biliary cirrhosis, inflammatory bowel disease, atopic dermatitis, inhalation allergy, sarcoidosis and graft-versus host disease. The polymorphism that affects risk to most of these immunopathologies is T244I at the border of the extracellular domain and the transmembrane region. The same region has recently been shown to harbor gain-of-function mutations in acute lymphoblastic leukemia. These studies have suggested new therapies that target the IL-7 pathway.
22356219 Heterogeneity of chronic pain. 2012 Feb 22 Chronic pain is a widespread public health issue that has many effects on physical, emotional and cognitive functions. An estimated 10-55% of all adults are thought to have chronic pain. Chronic pain is a multifactorial condition, caused by the complex interplay of nociceptive, neuropathic or mixed pathogenic mechanisms. Chronic pain is associated with specific and non-specific medical conditions such as cancer, HIV/AIDS, rheumatoid arthritis, fibromyalgia, osteoarthritis, low back pain or spinal stenosis and is broadly categorized as cancer pain and non-cancer pain. Evaluation of chronic pain requires a clear understanding of the nature of the pain and its underlying pathophysiology. Adequate assessment of pain, using validated tools, is an essential prerequisite of successful pain management. Unidimensional scales are useful for the measurement of pain intensity, while multidimensional scales measure both pain intensity and the extent to which pain interferes with life activity and emotional functioning. Patients should be reassessed and followed up in order to monitor progress and measure improvements in pain.
22335134 [S-adenosyl L-methionine in CNS diseases]. 2011 Nov S-adenosyl L-methionine (SAMe) is the natural, universal methyl group donor, participating in transmethylation reactions, known and commonly used as a dietary supplement since 1952. It plays an important role in the synthesis of neuromediators and melatonin and mechanisms of epigenetic regulation. The aim of this article is to review the literature about possibilities of SAMe application in the therapy of CNS diseases: depression, dementia syndromes, schizophrenia and somatic disorders. SAMe is the promising dietary supplement, which may be successfully used as a substance increasing effectiveness of the treatment of depression, with antidepressants in monotherapy in mild depressive states or depressive symptoms. SAMe addition to antipsychotic drug, may lead to the improvement of the quality of life and reduction of aggressiveness of patients. SAMe may be an effective substance in the therapy and prophylaxis of mild cognitive impairments and mild dementia syndrome. SAMe possesses some hepatoprotective action, so it may decrease the risk of the development of neoplasm, alcohol-induced liver disease (ALD) and cirrhosis. SAMe improves the functions of joints and decreases the experience of pain in rheumatoid arthritis (RA).
22230555 Human serum albumin: from bench to bedside. 2012 Jun Human serum albumin (HSA), the most abundant protein in plasma, is a monomeric multi-domain macromolecule, representing the main determinant of plasma oncotic pressure and the main modulator of fluid distribution between body compartments. HSA displays an extraordinary ligand binding capacity, providing a depot and carrier for many endogenous and exogenous compounds. Indeed, HSA represents the main carrier for fatty acids, affects pharmacokinetics of many drugs, provides the metabolic modification of some ligands, renders potential toxins harmless, accounts for most of the anti-oxidant capacity of human plasma, and displays (pseudo-)enzymatic properties. HSA is a valuable biomarker of many diseases, including cancer, rheumatoid arthritis, ischemia, post-menopausal obesity, severe acute graft-versus-host disease, and diseases that need monitoring of the glycemic control. Moreover, HSA is widely used clinically to treat several diseases, including hypovolemia, shock, burns, surgical blood loss, trauma, hemorrhage, cardiopulmonary bypass, acute respiratory distress syndrome, hemodialysis, acute liver failure, chronic liver disease, nutrition support, resuscitation, and hypoalbuminemia. Recently, biotechnological applications of HSA, including implantable biomaterials, surgical adhesives and sealants, biochromatography, ligand trapping, and fusion proteins, have been reported. Here, genetic, biochemical, biomedical, and biotechnological aspects of HSA are reviewed.
22140607 Nicotinamide Phosphoribosyltransferase in Human Diseases. 2011 Jan 7 Nicotinamide phosphoribosyltransferase (NAMPT) was first reported as a pre-B-cell colony enhancing factor in 1994 with little notice, but it has received increasing attention in recent years due to accumulating evidence indicating that NAMPT is a pleiotropic protein such as a growth factor, a cytokine, an enzyme and a visfatin. Now, NAMPT has been accepted as an official name of this protein. Because of NAMPT's multiple functions in a variety of physiological processes, their dysregulations have been implicated in the pathogenesis of a number of human diseases or conditions such as acute lung injury, aging, atherosclerosis, cancer, diabetes, rheumatoid arthritis and sepsis. This review will cover the current understanding of NAMPT's structure and functions with an emphasis on recent progress of nicotinamide phosphoribosyltransferase's pathological roles in various human diseases and conditions. Future directions on exploring its Terra incognita will be offered in the end.
22083586 Small molecule immunomodulatory drugs: challenges and approaches for balancing efficacy wi 2012 As the molecular pathobiology of immunologically based diseases, such as rheumatoid arthritis, has become clearer, pharmaceutical researchers have responded with highly efficacious and selective biological compounds. In contrast to older, nonspecific small-molecule therapeutics, the exquisite species sensitivity of monoclonal antibodies has introduced new challenges to preclinical safety studies. Repeated exposure of animals to biopharmaceutical compounds tends to be restricted in the species in which these compounds have pharmacological action, and it tends to stimulate antidrug immune responses with acceleration of clearance, thereby limiting the duration of repeat-dose studies and potentially resulting in hypersensitivity reactions. Thus, the safety testing of biopharmaceutical compounds has necessitated the use of relatively short-term studies in rodents, whereas nonhuman primates have become the primary tool for large-animal, repeat-dose studies. However, as the number of highly targeted and efficacious small-molecule immunomodulators rapidly increases, these molecules will be developed in a manner similar to that of other small molecules with regard to safety assessment. Because such approaches inherently push drug levels to achieve maximally tolerated doses, the pharmacologic specificity of these new small-molecule drugs may be lost as they affect additional receptors and pathways. Therefore, toxicologic pathologists must refamiliarize themselves with the consequences of profound immunosuppression in species other than nonhuman primates. The interrelationships of cytokine signaling and receptor biology are complex, highly integrated, and at times paradoxical, and the loss of specificity at high doses may result in unforeseen consequences caused by the impact on complex down-stream pathways that culminate in exaggerated and adverse responses. The species specificity of such responses may not be inherently familiar or anticipated.
22021955 Depression and suicide publication analysis, using density equalizing mapping and output b 2011 Jan BACKGROUND: Depression is a major cause of suicide worldwide. This association has been reflected by numerous scientific publications reporting about studies to this theme. There is currently no overall evaluation of the global research activities in this field. AIM: The aim of the current study was to analyze long-term developments and recent research trends in this area. MATERIAL AND METHODS: We searched the Web of Science databases developed by the Thompson Institute of Scientific Information for items concerning depression and suicide published between 1900 and 2007 and analyzed the results using scientometric methods and density-equalizing calculations. RESULTS: We found that publications on this topic increased dramatically in the time period 1990 to 2007. The comparison of the different Journals showed that the Archives of General Psychiatry had the highest average citation rate (more than twice that of any other Journal). When comparing authors, we found that not all the authors who had high h-indexes cooperated much with other authors. The analysis of countries who published papers on this topic showed that they published papers in relation to their Gross Domestic Product and Purchasing Power Parity. Among the G8 countries, Russia had the highest male suicide rate in 1999 (more than twice that of any of the other G8 countries), despite having published least papers and cooperating least with other countries among the G8. CONCLUSION: We conclude that, although there has been an increase in publications on this topic from 1990 to 2006, this increase is of a lower gradient than that of psoriasis and rheumatoid arthritis.
21742405 CD46 processing: a means of expression. 2012 Feb CD46 is a ubiquitously expressed type I transmembrane protein, first identified as a regulator of complement activation, and later as an entry receptor for a variety of pathogens. The last decade has also revealed the role of CD46 in regulating the adaptive immune response, acting as an additional costimulatory molecule for human T cells and inducing their differentiation into Tr1 cells, a subset of regulatory T cells. Interestingly, CD46 regulatory pathways are defective in T cells from patients with multiple sclerosis, asthma and rheumatoid arthritis, illustrating its importance in regulating T cell homeostasis. Indeed, CD46 expression at the cell surface is tightly regulated in many different cell types, highlighting its importance in several biological processes. Notably, CD46 is the target of enzymatic processing, being cleaved by metalloproteinases and by the presenilin/gamma secretase complex. This processing is required for its functions, at least in T cells. This review will summarize the latest updates on the regulation of CD46 expression and on its effects on T cell activation.
21586406 Systematic reviews of t'ai chi: an overview. 2012 Aug Several systematic reviews (SRs) have assessed the effectiveness of t'ai chi for many conditions including hypertension, osteoarthritis and fall prevention; however, their conclusions have been contradictory. The aim of this overview was to critically evaluate the SRs of t'ai chi for any improvement of medical conditions or clinical symptoms. English, Chinese and Korean electronic databases were searched for relevant articles, and data were extracted according to predefined criteria; 35 SRs met our inclusion criteria. They were related to the following conditions: cancer, older people, Parkinson's disease, musculoskeletal pain, osteoarthritis, rheumatoid arthritis (RA), muscle strength and flexibility, improving aerobic capacity, cardiovascular disease and risk factors, lowering resting blood pressure, osteoporosis or bone mineral density, type 2 diabetes, psychological health, fall prevention and improving balance, and any chronic conditions. In several instances, the conclusions of these articles were contradictory. Relatively clear evidence emerged to suggest that t'ai chi is effective for fall prevention and improving psychological health and was associated with general health benefits for older people. However, t'ai chi seems to be ineffective for the symptomatic treatment of cancer and RA. In conclusion, many SRs of t'ai chi have recently been published; however, the evidence is convincingly positive only for fall prevention and for improvement of psychological health.
21546804 Transverse divergent dislocation of elbow in a child: a case report and review of current 2011 May We present a case report on transverse divergent dislocation of the elbow, highlighting the spatial relation among the proximal radius, ulna, and distal humerus in this rare pediatric elbow injury and reasons leading to misinterpretation of radiographs. Elbow dislocation is a rare injury in children. It comprises only 6% of pediatric elbow injuries. Most pure dislocations are posterior, but they can occur in any direction. Divergent dislocation of the elbow is a subgroup of posterior dislocation, which is extremely rare. It is important that the pediatric emergency physician is aware, able to identify, and manage this injury. It is defined as a specific elbow dislocation in which the distal humerus is forced between the proximal radius and ulna, resulting in the divergence of the proximal forearm bones. Joint laxity is said to be a predisposing cause in pediatric age group. Atraumatic divergent dislocation of the elbow has been reported in the adults with rheumatoid arthritis. Imaging is challenging because there is no defined specific radiological views, therefore making the diagnosis difficult. This often leads to misdiagnosis or inappropriate treatment. A thorough understanding of mechanism of injury and basis for atypical radiological findings will help in identifying the injury early, and the simple Thompson technique to relocate the elbow will give an excellent functional outcome.
21466443 Fractalkine/CX3CR1 signalling in chronic pain and inflammation. 2011 Oct The development of new therapeutic approaches to the treatment of painful neuropathies requires a better understanding of the mechanisms that underlie chronic pain syndromes. There is increasing evidence that immune competent cells such as microglia contribute to the development of chronic pain states. Chemokines play a pivotal role in mediating neuronal-microglial communication which leads to increased nociception. Fractalkine (FKN) is structurally unique amongst the family of chemokines and their receptors and expressed both in the central nervous system and peripheral nerves, as well as in endothelial cells and lymphocytes. Signalling via the CX3CR1 receptor, FKN is able to mediate critical physiological functions necessary for immune regulation. In its soluble forms FKN mediates chemotaxis of immune cells whilst membrane bound FKN acts as an adhesion molecule mediating leukocyte capture and infiltration. As FKN/CX3CR1 is such a key signalling pair for homeostatic functions it is not surprising that it is implicated in a large number of diseases in which imbalance of the immune system is implied. Here we review the evidence that FKN/CX3CR1 mediates neuron-microglial communication in chronic pain states and is therefore key in the development of neuropathic pain. In addition, the contribution of FKN/CX3CR1 signalling to the pathogenesis and progression of two chronic inflammatory conditions, atherosclerosis and rheumatoid arthritis, are discussed.