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ID PMID Title PublicationDate abstract
20490591 Anti-ribonucleoproteins autoantibodies in patients with systemic autoimmune diseases. Rela 2011 Feb A common feature between patients with a certain group of systemic autoimmune pathologies (SAPs) with rheumatic component, such as lupus erythematosus (LE) in all its forms, is the presence of cutaneous photosensitivity (CP) as well as the existence of autoantibodies (Aabs). These Aabs have also high incidence in other SAPs that do not present CP, like primary Sjögren's syndrome and rheumatoid arthritis. Cutaneous photosensitivity is a condition that consists of an exacerbated skin reaction to solar radiations; its incidence can reach 90% in systemic LE. The mechanisms involved in the development of CP have been extensively studied focusing on different approaches; however, the exact mechanism has not been fully elucidated yet. There are many theories that relate specifically the presence of circulating anti-Ro/SS-A Aabs with the CP phenomenon, though there are several studies which are in disagreement. In this study, we evaluated the Aabs profile (anti-Ro/SS-A 52 kDa, anti-Ro/SS-A 60 kDa, anti-La/SS-B, anti-Sm and ANAs) as well as their titer or reactivity, in a local cohort of 169 patients with SAPs. We related those Aabs profiles and titers with the presence or absence of CP, and we found that there was no significant association between the presence of anti-Ro/SS-A Aabs and the occurrence of CP. On the other hand, a statistically significant positive association was found between CP and high reactivity anti-Sm Aabs, though this fact could be biased by the incidence of both events in SLE patients. To sum up, in the particular population studied, there is no direct relationship between anti-Ro/SS-A Aabs and CP, which is in agreement with some authors and in disagreement with many others, contributing to the endless discussion of this issue.
20448816 Perforation rates of cervical pedicle screw insertion by disease and vertebral level. 2010 Mar 4 BACKGROUND: Different perforation rates for cervical pedicle screws by disease are expected in relation to bone quality and pedicle morphology; however, no report comparing pedicle screw perforation rate by disease had previously been published. This study investigated the perforation rates of pedicle screws inserted to cervical pedicle by disease and vertebral level using a CT-based navigation system. MATERIALS/METHODS: Fifty-three patients who underwent cervical pedicle screw insertion using CT based navigation system were studied. Diseases included rheumatoid arthritis (RA) (24 cases), destructive spondyloarthropathy (DSA) (10), cervical spondylotic myelopathy (CSM) (9), spine tumor (6), and cervical spondylotic myelopathy associated with athetoid cerebral palsy (CP) (4). Screw perforation rates for cervical pedicle screws were studied. Major perforation was defined as perforation 50% of screw diameter or more. RESULTS: Major perforation rate by disease from C3 to C7 was as follows: spine tumor (0/24, 0%), RA (2/59, 3.4%), DSA (3/65, 4.6%), CP (2/20, 10.0%), and CSM (6/40, 15.0%). There were no clinically important complications such as vertebra arterial injury, spinal cord injury, or nerve root injury caused by any screw perforation. Major perforation rate by vertebral level was: C2(2/30, 6.7%), C3(4/49, 8.2%), C4(6/43, 14.0%), C5(1/32, 3.1%), C6(1/41, 2.4%), and C7(1/45, 2.2%), showing highest rate for C4, followed by C3. CONCLUSIONS: Cervical pedicle screw perforation rate by disease was higher in CSM compared to RA and DSA. The perforation rate by vertebral level was higher for C4 and C3, in this order.
20382196 Serum IL-7 and G-CSF in major depressive disorder. 2010 Aug 16 Major depressive disorder (MDD) has been associated with dysregulated immune systems and impaired T cell function, but data on depression-related alterations in the levels of immunomodulatory growth factors are scarce. In order to further clarify the mechanisms underlying immune system dysregulation in depressed subjects, we examined the associations between MDD and serum levels of two immunomodulatory growth factors, interleukin (IL)-7 and granulocyte-colony stimulating factor (G-CSF), in 122 subjects (MDD with long-term symptomatology, n=61; controls, n=61). The MDD subjects had lowered levels of IL-7. In a model adjusted for age, gender and body mass index, subjects in the lowest tertile of IL-7 had a 3.4-fold increased likelihood for MDD (p=0.010). Further adjustments for sleep disturbances, alcohol use, smoking, and metabolic syndrome did not alter these findings. Moreover, the exclusion of subjects with rheumatoid arthritis, coronary heart disease, or the use of non-steroidal anti-inflammatory medications or oral corticosteroids only slightly attenuated the findings. The G-CSF levels did not differ between the two groups. The lowering of the serum levels of IL-7, a regulator of T cell homeostasis, in MDD subjects may underlie the depression-related impaired T cell function.
20338742 Increased serum IL-17 is an independent risk factor for severe asthma. 2010 Aug BACKGROUND: IL-17 expression was found to be associated with many inflammatory diseases in humans, such as rheumatoid arthritis, asthma, systemic lupus erythematosus and allograft rejection and many in vitro studies have indicated a proinflammatory function for IL-17. OBJECTIVE: Prognostic value of increased serum IL-17 in asthma patients. METHODS: Serum IL-17 (ELISA) was measured in 85 asthma patients (pts), mean age 46.99 +/- 14.1 years, 61% females, 23 mild persistent, 26 moderate persistent and 36 severe persistent asthma. Using multiple regression analysis (STATISTICA 7), increased serum IL-17 (>20 pg/ml) was tested as risk factor for severe asthma in comparison with "traditional" risk factors: smoke, NSAID intolerance, obesity, chronic rhinosinusitis, blood eosinophilia, FEV(1) at baseline < 50% predicted (low FEV(1)). RESULTS: Medium serum IL-17 values were 14.21 pg/ml in mild asthma, 12.22 pg/ml in moderate asthma and 24.72 pg/ml in severe asthma. IL-17 values > 20 pg/ml were encountered in 3(13%) mild asthma pts (p < 0.001 vs. severe asthma), 2(8%) moderate asthma pts. (p < 0.001 vs. severe asthma), and in 11(31%) severe asthma pts. For severe asthma multiple regression analysis revealed as independent risk factors IL-17 (p = 0.000290), NSAID intolerance (p = 0.000585) and low FEV(1) (p = 0.000059). CONCLUSIONS: IL-17 is increased in severe asthma compared to mild/moderate forms of the disease and values above 20 pg/ml are an independent risk factor for severe asthma.
20067787 A novel compound, NP-184, inhibits the vascular endothelial growth factor induced angiogen 2010 Mar 25 Angiogenesis is observed in many diseases, such as tumor progression, diabetes and rheumatoid arthritis; it is a process that involves proliferation, migration, differentiation and tube formation of endothelial cells. Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis by induction of these endothelial functions. Thus, inhibition of these critical angiogenic steps is a practical therapeutic strategy for those diseases. NP-184 is a substituted benzimidazole analogue which exhibits a potent anti-thrombotic activity. In this report, NP-184 inhibited the viability of human umbilical vascular endothelial cells (HUVEC) in a concentration-dependent manner, and caused cell apoptosis as examined by cell-cycle analysis and Annexin V staining with flow cytometry. NP-184 also concentration-dependently inhibited the HUVEC migration, tube formation on Matrigel, and rat aortic ring sprouting stimulated by VEGF. Regarding the intracellular signal transduction, NP-184 concentration-dependently interfered with the activation of AKT, ERK and the nuclear translocation of NF-kappaB. In vivo study showed that NP-184 dose-dependently reduced angiogenesis in Matrigel plug assay. These results indicate that NP-184 is a potential candidate for developing the treatment of angiogenesis related-diseases.
19923448 Role of CX3CL1/fractalkine in osteoclast differentiation and bone resorption. 2009 Dec 15 The recruitment of osteoclast precursors toward osteoblasts and subsequent cell-cell interactions are critical for osteoclast differentiation. Chemokines are known to regulate cell migration and adhesion. CX3CL1 (also called fractalkine) is a unique membrane-bound chemokine that has dual functions for cells expressing its receptor CX3CR1: a potent chemotactic factor in its soluble form and a type of efficient cell adhesion molecule in its membrane-bound form. In this paper, we demonstrate a novel role of CX3CL1 in osteoblast-induced osteoclast differentiation. We found that osteoclast precursors selectively expressed CX3CR1, whereas CX3CL1 is expressed by osteoblasts. We confirmed that soluble CX3CL1 induced migration of bone marrow cells containing osteoclast precursors, whereas immobilized CX3CL1 mediated firm adhesion of osteoclast precursors. Furthermore, a blocking mAb against CX3CL1 efficiently inhibited osteoclast differentiation in mouse bone marrow cells cocultured with osteoblasts. Anti-CX3CL1 also significantly suppressed bone resorption in neonatal mice by reducing the number of bone-resorbing mature osteoclasts. Collectively, CX3CL1 expressed by osteoblasts plays an important role in osteoclast differentiation, possibly through its dual functions as a chemotactic factor and adhesion molecule for osteoclast precursors expressing CX3CR1. The CX3CL1-CX3CR1 axis may be a novel target for the therapeutic intervention of bone resorbing diseases such as rheumatoid arthritis, osteoporosis, and cancer bone metastasis.
19874232 Immunosuppressive effect of ethanol extract of Artemisia annua on specific antibody and ce 2009 Artemisia annua has been widely used to treat autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis in traditional Chinese medicine. In this study, the ethanol extract of A. annua (EEAA) was evaluated for the immunosuppressive potentials on mice splenocyte proliferation in vitro, and the specific antibody and cellular immune responses in the ovalbumin (OVA)-immunized mice. EEAA significantly suppressed concanavalin A (Con A)- and lipopolysaccharide (LPS)-stimulated splenocyte proliferation in vitro in a concentration-dependent manner. EEAA also significantly suppressed Con A-, LPS- and OVA-induced splenocyte proliferation in the OVA-immunized mice in a dose-dependent manner. Meanwhile, the OVA-specific serum IgG, IgG1 and IgG2b antibody levels in the OVA-immunized mice were markedly reduced by EEAA. The results suggest that EEAA could suppress the cellular and humoral response in mice. This study provided evidence to understand the therapeutic effects of A. annua for treatment of some autoimmune diseases and an immunosuppressive natural products to further researches to be developed as immunosuppressant.
19843413 Identification of new risk factors for pneumonia: population-based case-control study. 2009 Oct BACKGROUND: Certain conditions are established as risk factors for community-acquired pneumonia. There are a number of other conditions that may also be risk factors, but information on these is limited. AIM: To determine new independent risk factors for community-acquired pneumonia using a very large primary care database. DESIGN OF STUDY: Nested case-control study. SETTING: Four hundred and forty-three general practices in the UK contributing to the QRESEARCH database. METHOD: A total of 17 172 incident cases of all ages diagnosed with pneumonia between 1996 and 2005 were matched with up to five controls by age, sex, general practice, and calendar year. Associations between pneumonia and each established condition and potential risk factors were determined with odds ratios (ORs), using multiple conditional logistic regression analysis adjusted for smoking, socioeconomic status, and use of influenza and pneumococcal vaccines. RESULTS: The analysis confirmed the higher risk of pneumonia among patients with at least one of the established risk factors; the adjusted OR was 2.29 (95% confidence interval [CI]=2.20 to 2.39). In addition, patients with the following conditions had a higher risk of pneumonia despite adjustment for known risk factors and confounders: stroke or transient ischaemic attack, rheumatoid arthritis, Parkinson's disease, cancers, multiple sclerosis, dementia, and osteoporosis. The adjusted OR for pneumonia among patients without an established risk factor but with at least one of the new conditions was 2.44 (95% CI=2.24 to 2.65). CONCLUSION: As well as confirming some established risk factors, this study has determined seven new independent risk factors for community-acquired pneumonia.
19778284 Association between IRF-5 polymorphisms and risk of acute coronary syndrome. 2010 Jan Previous studies suggested that genetic polymorphisms in interferon regulatory factor 5 (IRF-5) are implicated in the susceptibility to a range of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease. Recently, IRF-5 has been implicated in inflammatory processes that are associated with excessive remodeling and atherosclerosis. Our purpose was to investigate the association between the IRF-5 polymorphisms and the risk of acute coronary syndrome (ACS) in a Chinese population. The 5 bp indel (insertion/deletion) (CGGGG) polymorphism, located 64 bp upstream of the alternative exon 1a of IRF-5 gene, and the deletion of 30 bp in exon 6 of IRF-5 gene were analyzed among 148 patients with ACS and 246 controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism strategy and direct sequencing. The frequencies of (CGGGG)(3)(CGGGG)(4) genotype and (CGGGG)(4) allele in ACS patients were significantly higher than those in control subjects (p = 0.018, odds ratio [OR] = 1.76, 95% confidence interval [CI]: 1.10-2.81; p = 0.028, OR = 1.62, 95% CI: 1.05-2.50, respectively). However, no significant relationship between the 30 bp exon 6 polymorphism of the IRF-5 gene and the risk of ACS was observed (p = 0.770, OR = 0.96, 95% CI: 0.72-1.28). The 5 bp indel (CGGGG) polymorphism of the IRF-5 gene may be associated with susceptibility to ACS.
19740385 Clone clusters in autoreactive CD4 T-cell lines from probable multiple sclerosis patients 2009 Oct We developed a method for selectively propagating disease-related autoreactive T-cell lines (auTCLs) based on their increased resistance to apoptosis. The generated auTCLs homogeneously co-express CD45RO and CD49a, adhere strongly to extracellular matrix proteins and express high interleukin-17 (IL-17) messenger RNA levels, resembling a T-cell subset proposed to transmigrate into tissues and induce systemic and local inflammation in rheumatoid arthritis. The combinations of T-cell oligoclones that comprise probable multiple sclerosis (pMS) disease-related lines use a unique portfolio of T-cell receptor beta-chain variable allele (BV genes) combinations forming 'disease-specific cluster patterns'. The auTCL derived from different patients and from different myelin epitopes display striking similarities in BV gene allele clusters and are derived primarily from a disease-prone hotspot residing in the BV gene locus between Vbeta6 and Vbeta9. Conversely, healthy subject TCLs use different BV gene allele sets, forming 'healthy responder usage formats'. These formats were absent from the pMS patient V-beta gene allele combinations evaluated in this study. Hierarchical clustering of the BV gene combinations, distinguish three pMS auTCL groups, implying existence of up to three disease-related immune response patterns. These subgroup patterns may reflect different disease subclasses or alternatively they may suggest immune reactivity to different aetiological agents. Analyses of clonal-clustering patterns may potentially aid in subclassification of MS or in characterizing aetiological agents of this disease.
19689368 Colony-stimulating factor-1 receptor inhibitors for the treatment of cancer and inflammato 2009 FMS is the exclusive receptor tyrosine kinase for colony-stimulating factor-1 (CSF-1, also known as M-CSF), which regulates the survival, proliferation, differentiation, and function of macrophage lineage cells. Since CSF-1 is over-expressed in many tumors and at sites of inflammation, small molecule inhibitors of CSF-1 appear to offer an attractive strategy for reducing macrophage numbers associated with cancer as well as autoimmune and inflammatory disease, such as rheumatoid arthritis (RA). Numerous FMS inhibitors with structurally distinct chemotypes have been developed and exhibit potent in vitro activity, but only a limited number of compounds have progressed clinically due to poor selectivity. To date, only a handful of FMS inhibitors have been tested in models of metastatic bone disease and RA. This review will summarize the biology of FMS and its function in bone physiology, inflammation, immunity, and cancer. In addition, efforts directed towards identifying FMS-selective small molecule inhibitors as well as the advancement of non-selective inhibitors in the clinic will be highlighted. Furthermore, emerging monoclonal antibody-based therapeutic strategies specifically targeting M-CSF will be described.
19541589 Inflammatory cells and chemokines sustain FGF2-induced angiogenesis. 2009 Jun Angiogenesis and inflammation are closely integrated processes in a number of physiological and pathological conditions, including wound healing, psoriasis, diabetic retinopathy, rheumatoid arthritis, arteriosclerosis, and cancer. Fibroblast growth factor-2 (FGF2) belongs to the family of the heparin-binding FGF growth factors. FGF2 exerts its pro-angiogenic activity by interacting with various endothelial cell surface receptors, including tyrosine kinase receptors, heparan-sulfate proteoglycans, and integrins. Elevated levels of FGF2 have been implicated in the pathogenesis of several diseases characterized by a deregulated angiogenic/inflammatory response. FGF2 induces the expression of a wide repertoire of inflammation-related genes in endothelial cells, including pro-inflammatory cytokines/chemokines and their receptors, endothelial cell adhesion molecules, and components of the prostaglandin pathway. Consistent with this pro-inflammatory signature, in vivo evidence points to a non-redundant role for chemokines and infiltrating monocytes/macrophages in FGF2-driven neovascularization. This review will focus on the cross-talk between FGF2 and the inflammatory response in the modulation of blood vessel growth.
19404646 Increased expression of CD154 and FAS in SLE patients' lymphocytes. 2009 Dec An increased level of apoptotic material and B cell activation leading to autoantibody production are hallmarks of systemic lupus erythematoses (SLE). Increased FAS expression, apoptosis, and CD154-mediated signaling, enabling T–B cell interaction are involved in the pathogenesis of SLE. This study addresses the expression profile of CD154 and FAS in the peripheral blood of patients with SLE, rheumatoid arthritis (RA) and normal healthy control donors. Surface markers on peripheral blood T and B cells from patients and healthy control donors were assessed using flow cytometry. The expression of CD154 and FAS were significantly increased in T and B cells of SLE patients as compared to healthy control donors and RA patients. In SLE and RA patients, FAS expression strongly correlated with CD154 expression on T cells, which was not found in healthy control donors. FAS expression was also associated with the occurrence of anti-DNA antibodies. We demonstrate high CD154 and FAS expression as a characteristic feature of SLE. This pattern may reflect simultaneous activation of apoptosis and activation of B–T cell interaction in SLE.
19346950 Novel screening tools for latent tuberculosis: time to leave an old friend? 2009 May PURPOSE OF REVIEW: Therapeutic inhibition of tumour necrosis factor-alpha strongly increases the risk of reactivation in latent tuberculosis infection. Recent blood tests based on antigen-specific T cell response and measuring production of interferon-gamma, so called interferon-gamma release assays (IGRAs), are promising novel tools to identify infected patients. The performance of diagnostic testing for latent tuberculosis infection in patients with rheumatic diseases will be discussed. RECENT FINDINGS: In patients with rheumatoid arthritis, IGRAs are more sensitive and more specific than traditional tuberculin skin testing. They are unaffected by Bacillus-Calmette-Guérin vaccination and most nontuberculous mycobacteria. Most comparative studies show a better performance of the IGRAs than tuberculin skin testing in terms of a higher specificity. The rate of indeterminate results may be affected by glucocorticoids and the underlying disease but appears independent of disease-modifying antirheumatic drugs. Despite using identical Mycobacterium tuberculosis antigens, the two commercially available tests show differences in clinical performance. SUMMARY: The current information about the performance of the tuberculin skin testing and the IGRAs in the detection of latent tuberculosis infection in patients with rheumatic diseases strongly suggest a clinically relevant advantage of the IGRAs. Their use will help to reduce overuse and underuse of preventive treatment in tumour necrosis factor inhibition.
19341825 Effect of enzymatic deimination on the conformation of recombinant prion protein. 2009 Aug Deimination is the post-translational conversion of arginine residues to citrulline. It has been implicated as a causative factor in autoimmune diseases such as multiple sclerosis and rheumatoid arthritis and more recently, as a marker of neurodegeneration. We have investigated the effect of the post-translational modification of arginine residues on the structure of recombinant ovine prion protein. Deiminated prion protein exhibited biophysical properties characteristic of the scrapie-associated conformer of prion protein viz. an increased beta-sheet secondary structure, congophilic structures indicative of amyloid and proteinase K resistance which could be templated onto normal unmodified prion protein. In the light of these findings, a potential role of post-translational modifications to prion protein in disease initiation or propagation is discussed.
19327224 Internet use in rheumatology outpatients in 2006: gender less important. 2009 Jan OBJECTIVE: Exploring patients' Internet use, their online needs and requirements, expectations and attitudes towards the Internet is mandatory to effectively provide interactive online applications and information. METHODS: Within a prospective study, 153 consecutive outpatients with rheumatoid arthritis, systemic lupus erythematosus or spondyloarthritis answered a paper-based questionnaire investigating their Internet use, interests, pattern and degree of utilization. Sociodemographic and functional disability data were collected. The data were compared with our survey of 2001 and to the normal German population. RESULTS: Patients were predominantly female (69.3%; n.s.). Mean age was 45.7+/-14.4 years (n.s.). 68.6% (+18.6%, p=0.0027) reported regular Internet use for 5.0+/-2.6 yrs. Internet use in 2006 is still age- and education-dependent (p<0.001, p=0.003). Differences by gender observed in 2001 no longer existed as women increased their Internet use from 2.9 to 6.1 hours/week (p=0.001, p=0.0006). Searching for health-related information remained an important topic. Interest in e-communication and interactive applications strongly increased. Independently of gender and functional disability, patients' future online interests focussed on information on diseases, medications, health care providers and patient education. Confidence in the Internet and reliability of information were rated unchanged since 2001. CONCLUSION: Gender no longer has significant impact on Internet use. The great potentials of Internet services-well accepted by patients and contributing substantially to more effective and improved disease (self-) management strategies-should encourage rheumatologists to provide interactive applications and high-quality information on Internet platforms and in routine patient care. Continuous research to explore the effects of Internet-delivered information on patients' attitudes,expectations, behaviour and outcome is required.
19309350 Translational mini-review series on immunology of vascular disease: accelerated atheroscle 2009 Jun Premature atherosclerosis has been observed during the course of different systemic inflammatory diseases such as rheumatoid arthritis and sytemic lupus erythematosus. Remarkably, relatively few studies have been published on the occurrence of accelerated atherosclerosis in patients with vasculitis. In giant cell arteritis (GCA), mortality because of ischaemic heart disease is not increased. In addition, intima media thickness (IMT) is lower in patients with GCA than in age-matched controls. In contrast, IMT is increased significantly in Takayasu arteritis, another form of large vessel vasculitis occurring in younger patients. In Takayasu arteritis and in Kawasaki disease, a form of medium-sized vessel vasculitis, accelerated atherosclerosis has been well documented. In small vessel vasculitis because of anti-neutrophil cytoplasmic autoantibodies-associated vasculitis, cardiovascular diseases are a major cause of mortality. IMT measurements reveal conflicting results. During active disease these patients experience acceleration of the atherosclerotic process. However, when inflammation is controlled, these patients have atherosclerotic development as in healthy subjects. Several risk factors, such as diabetes and hypertension, are present more often in patients with vasculitis compared with healthy controls. In addition, steroids may be pro-atherogenic. Most importantly, many patients have impaired renal function, persistent proteinuria and increased levels of C-reactive protein, well-known risk factors for acceleration of atherosclerosis. Enhanced oxidation processes, persistently activated T cells and reduced numbers of regulatory T cells are among the many pathophysiological factors that play a role during acceleration of atherogenesis. Finally, autoantibodies that may be relevant for acceleration of atherosclerosis are found frequently in elevated titres in patients with vasculitis. Because patients have an increased risk for cardiovascular events, vasculitis should be treated with as much care as possible. In addition, treatment should be considered with angiotensin-converting-enzyme inhibitors and/or angiotensin receptor-1 blockers, statins and acetylsalicyl acid. Finally, classical risk factors for cardiovascular disease should be monitored and treated as much as possible.
19309046 Idiopathic chondrolysis treated with etanercept. 2009 Mar Idiopathic chondrolysis of the hip in children has been well documented in the literature. The insidious nature of the symptoms and lack of early radiographic findings and diagnostic testing often delay diagnosis. Children often report a stiff, painful hip and have an associated limp in the absence of trauma or constitutional symptoms. Despite these symptoms it remains a poorly understood diagnosis with no identifiable cause. Some have speculated an inflammatory cause, as this disease exhibits joint space narrowing, presumably due to enzymatic activity similar to juvenile rheumatoid arthritis. Despite case reports attempting traction, physical therapy, nonsteroidal anti-inflammatories, steroids, and even operative intervention, no current treatment regimen exists that offers proven appreciable benefit. We hypothesized the powerful anti-inflammatory properties of etanercept would provide symptomatic and radiographic improvement of idiopathic chondrolysis of the hip. This article presents a case of an adolescent boy with a stiff, painful left hip that failed treatment with traction, physical therapy, naproxen, and methotrexate, prior to initiating etanercept. After 1 year of daily etanercept therapy, the patient's hip motion improved in all directions and his pain completely resolved. This novel therapeutic approach offered symptomatic relief and radiographic improvement, and may provide an effective treatment strategy for this difficult disease.
19158813 The HLA genomic loci map: expression, interaction, diversity and disease. 2009 Jan The human leukocyte antigen (HLA) super-locus is a genomic region in the chromosomal position 6p21 that encodes the six classical transplantation HLA genes and at least 132 protein coding genes that have important roles in the regulation of the immune system as well as some other fundamental molecular and cellular processes. This small segment of the human genome has been associated with more than 100 different diseases, including common diseases, such as diabetes, rheumatoid arthritis, psoriasis, asthma and various other autoimmune disorders. The first complete and continuous HLA 3.6 Mb genomic sequence was reported in 1999 with the annotation of 224 gene loci, including coding and non-coding genes that were reviewed extensively in 2004. In this review, we present (1) an updated list of all the HLA gene symbols, gene names, expression status, Online Mendelian Inheritance in Man (OMIM) numbers, including new genes, and latest changes to gene names and symbols, (2) a regional analysis of the extended class I, class I, class III, class II and extended class II subregions, (3) a summary of the interspersed repeats (retrotransposons and transposons), (4) examples of the sequence diversity between different HLA haplotypes, (5) intra- and extra-HLA gene interactions and (6) some of the HLA gene expression profiles and HLA genes associated with autoimmune and infectious diseases. Overall, the degrees and types of HLA super-locus coordinated gene expression profiles and gene variations have yet to be fully elucidated, integrated and defined for the processes involved with normal cellular and tissue physiology, inflammatory and immune responses, and autoimmune and infectious diseases.
19061941 Cloning, characterisation, and comparative quantitative expression analyses of receptor fo 2009 Apr 1 RAGE is a member of the immunoglobulin superfamily of cell surface molecules playing key roles in pathophysiological processes, e.g. immune/inflammatory disorders, Alzheimer's disease, diabetic arteriosclerosis and tumourigenesis. In humans 19 naturally occurring RAGE splicing variants resulting in either N-terminally or C-terminally truncated proteins were identified and are lately discussed as mechanisms for receptor regulation. Accordingly, deregulation of sRAGE levels has been associated with several diseases e.g. Alzheimer's disease, Type 1 diabetes, and rheumatoid arthritis. Administration of recombinant sRAGE to animal models of cancer blocked tumour growth successfully. In spite of its obvious relationship to cancer and metastasis data focusing sRAGE deregulation and tumours is rare. In this study we screened a set of tumours, healthy tissues and various cancer cell lines for RAGE splicing variants and analysed their structure. Additionally, we analysed the ratio of the mainly found transcript variants using quantitative Real-Time PCR. In total we characterised 24 previously not described canine and 4 human RAGE splicing variants, analysed their structure, classified their characteristics, and derived their respective protein forms. Interestingly, the healthy and the neoplastic tissue samples showed in majority RAGE transcripts coding for the complete receptor and transcripts showing insertions of intron 1.