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ID PMID Title PublicationDate abstract
19342680 IL-20 is regulated by hypoxia-inducible factor and up-regulated after experimental ischemi 2009 Apr 15 IL-20, an IL-10 family member, is involved in various inflammatory diseases, such as psoriasis, rheumatoid arthritis, and atherosclerosis. We investigated whether hypoxia in vitro and an in vivo model of ischemic stroke would up-regulate IL-20 expression. In vitro, IL-20 expression increased in hypoxic HaCaT, HEK293 cells, chondrocytes, monocytes, and glioblastoma cells. Inhibition of hypoxia-inducible factor 1alpha inhibited CoCl(2)-induced IL-20 expression. We identified two putative hypoxia response elements in the human il20 gene promoter. Promoter activity assays showed that CoCl(2) mimicked hypoxia-activated luciferase reporter gene expression. In vivo, experimental ischemic stroke up-regulated IL-20 in the sera and brain tissue of rats. IL-20 stained positively in glia-like cells in peri-infarcted lesions, but not in contralateral tissue. Administration of IL-20 mAb ameliorated ischemia-induced brain infarction of rats after experimental ischemic stroke. In vitro, RT-PCR analysis showed that glioblastoma cells, GBM8901, expressed IL-20 and its receptor subunits IL-20R1, IL-20R2, and IL-22R1. IL-20 induced cell proliferation in GBM8901 cells by activating the JAK2/STAT3 and ERK1/2 pathways. IL-20 also induced production of IL-1beta, IL-8, and MCP-1 in GBM8901 cells. We conclude that IL-20 was responsive to hypoxia in vitro and in the ischemic stroke model and that up-regulation of IL-20 in the ischemic brain may contribute to brain injury.
19188484 Migration inhibitory factor (MIF) released by macrophages upon recognition of immune compl 2009 May Deposition of immune complexes (IC) triggers Fc gamma R-dependent inflammation, leading to tissue damage in rheumatoid arthritis, systemic lupus erythematous, immune glomerulonephritis, and several immune vasculitides. Evidences support a role for macrophage migration inhibitory factor (MIF) in a number of inflammatory diseases, but the triggering of its secretion and its physiopathological role upon IC deposition remain elusive. Herein, we show that human macrophages secreted MIF after IC recognition, which in turn controlled the secretion of TNF. Macrophages from Mif-/- mice produced smaller amounts of TNF when stimulated with IgG-opsonized erythrocytes than wild-type (WT) cells. Using passive reverse Arthus reaction in the peritoneum and lungs as a model for IC-induced inflammation, we demonstrated that Mif-/- mice had a milder response, observed by reduced neutrophil recruitment, vascular leakage, and secretion of TNF, MIP-2, and keratinocyte-derived chemokine compared with WT controls. Adoptive transfer of alveolar macrophages from WT to Mif-/- mice rescued pulmonary neutrophil recruitment and TNF production upon passive reverse Arthus reaction. Our study indicates that Arthus inflammatory reaction is largely dependent on MIF and poses macrophages as a source of the MIF released upon IC recognition. These results give experimental support to the proposition that blockade of MIF might constitute an adjunctive, therapeutic approach to IC disease.
19187805 Functional imaging of inflammatory diseases using nuclear medicine techniques. 2009 Mar Molecular imaging with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) is increasingly used to diagnose, characterize, and monitor disease activity in the setting of inflammatory disorders of known and unknown etiology. These disorders include sarcoidosis, atherosclerosis, vasculitis, inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and degenerative joint disease. Gallium-67 ((67)Ga) citrate, labeled leukocytes with technetium-99m ((99m)Tc) or indium-111 ((111)In), and (18)F-fluorodeoxyglucose (FDG) represent the most widely used radiopharmaceutical agents. However, other preparations, such as labeled murine monoclonal antigranulocyte antibodies and labeled human polyclonal nonspecific immunoglobulin G, chemotactic peptides, interleukins, chemokines, and liposomes, have been used to image inflammation. Also, (99m)Tc nanocolloid scintigraphy has been found to be suitable for bone and joint diseases, especially RA. Among the single photon emitting imaging agents, the recommended radiotracer for abdominal inflammation has been (99m)Tc-hexamethylpropylene amine oxime (HMPAO)-labeled leukocytes. During the last several years, FDG-PET imaging has been shown to have great value for the detection of inflammation and has become the centerpiece of such initiatives. This very powerful technique will play an increasingly important role in the management of patients with inflammatory conditions. FDG-PET can provide valuable information in patients with pulmonary and extrapulmonary sarcoidosis, and is a useful tool for testing the efficacy of various treatments. FDG-PET combined with computed tomography holds great promise for assessing atherosclerosis of the large arteries. This modality is very sensitive in detecting large-vessel vasculitis and can be used to monitor the disease course. FDG-PET is also being used to study the inflamed synovial joints both in the experimental and clinical settings, especially for the investigation and management of RA and degenerative joint disease. This technique also has the potential to become the imaging modality of choice in assessing IBD, replacing radiolabeled autologous leukocyte imaging in this setting. Detection of inflammation in the lungs and airways may improve our knowledge about a multitude of disorders that affect these structures. Therefore, functional imaging, led by FDG-PET imaging, is likely to play an increasingly critical role in assessing inflammatory disorders of known and unknown etiologies, and will improve their management immensely in the future.
19111972 Transthoracic ultrasound in the evaluation of pulmonary fibrosis: our experience. 2009 May The purpose of this study was to identify the ultrasonographic features of mild, moderate and severe pulmonary fibrosis. Between December 2005 and November 2007, transthoracic ultrasonography (US) was performed by a single operator with specific training in lung sonography on 84 consecutive patients (51 males and 33 females, aged 46 to 73 y) with pulmonary fibrosis. The obtained data were compared with those from a sample of 162 healthy subjects (78 men and 84 women, aged 18 to 76 y). The disease was idiopathic (biopsy confirmed) in 53/84 cases (63%). In the remaining (all histologically confirmed) cases, it was associated with systemic sclerosis (n = 18), rheumatoid arthritis (n = 4), mixed connective tissue disease (n = 4), Sjogren syndrome (n = 4), polymyositis (n = 2) or primary biliary cirrhosis (n = 1). Disease severity was classified as mild, moderate or severe based on clinical findings and the results of standard chest radiography, high-resolution computed tomography and pulmonary function tests. Pulmonary fibrosis was associated with the following US findings: (1) fragmented, irregular thickening (micro3 mm) of the "pleural line" distributed over the whole surface of the lung, especially in the lower posterior lobe (observed in all 84 patients); (2) subpleural cysts (seen in 57/84 (68%) cases of moderate-severe disease); (3) reduction or absence of the physiological "gliding sign" related to disease severity (observed in 33/84 to 39% cases); and (4) increased number of horizontal (and to a lesser extent vertical) reverberation artifacts (seen in 41 patients with advanced fibrosis, 34% of the total series). All abnormalities were detected in both lungs. Although lung biopsy is still the gold standard for diagnosis of interstitial lung disease, transthoracic ultrasound can document early and late-stage changes associated with this disease.
19048257 Hyperuricemia and its related factors in an urban population, Izmir, Turkey. 2009 Jun The aim of this study was to examine the prevalence of hyperuricemia and its associated factors in an urban area of Izmir, located in western Turkey. Our study group was selected by computerized sampling from the participants of a larger population-based study searching for the prevalence of rheumatoid arthritis in Balcova and Narlidere districts of Izmir. A total of 132 subjects (69 women and 63 men) were included in this study. Serum uric acid, glucose, creatinine and lipid levels were studied. Body composition along with body fat percentage was determined anthropometrically. A total of 16 subjects had hyperuricemia (4 women and 12 men). The overall prevalence of hyperuricemia was 12.1% and the mean uric acid level was 4.9 +/- 1.3 mg/dl. Males had significantly higher uric acid levels than females (P < 0.05; 5.5 +/- 1.3 vs. 4.3 +/- 1.1 mg/dl, respectively). The prevalence of hypertension, diabetes, obesity and metabolic syndrome was 24.4, 5.3, 28 and 26.5%, respectively. There was no gouty subject. Sum of skinfold thickness (SFT) measurements and creatinine levels were the independent predictors of hyperuricemia (beta = 0.45, 0.47, respectively). Uric acid measurement is important not only for inflammatory rheumatic disorders but also for predicting metabolic syndrome and related coronary artery disease. There is sex difference in uric acid levels in favor of women most probably explained by gonadal hormones. Hyperuricemia is significantly predicted by anthropometric measure of SFT which is a simple clinical screening method along with creatinine levels.
19000786 A review of the current use of rituximab in autoimmune diseases. 2009 Jan Rituximab is a human/murine chimeric monoclonal antibody primarily used for treating non-Hodgkin's B-cell lymphoma. Recently it has also been used in the treatment of several autoimmune diseases. A literature review was conducted to determine the efficacy of rituximab in the treatment of some of these autoimmune diseases. Multiple mechanisms proposed for the rituximab mediated B cell depletion are also discussed. The efficacy of rituximab is well-established and it is FDA approved for treatment of Rheumatoid arthritis. In this review, data on the use of rituximab is presented from 92 studies involving 1197 patients with the following diseases: systemic lupus erythematosus, idiopathic thrombocytopenic purpura, anti-neutrophil cytoplasmic antibody associated vasculitis, Grave's disease, autoimmune hemolytic anemia, pemphigus vulgaris, hemophilia A, cold agglutinin disease, Sjogren's syndrome, graft vs. host disease, thrombotic thrombocytopenic purpura, cryoglobulinemia, IgM mediated neuropathy, multiple sclerosis, neuromyelitis optica, idiopathic membranous nephropathy, dermatomyositis, and opsoclonus myoclonus. The efficacy varies among different autoimmune diseases. The cumulative data would suggest that in the vast majority of studies in this review, RTX has a beneficial role in their treatment. While rituximab is very effective in the depletion of B cells, current research suggests it may also influence other cells of the immune system by re-establishing immune homeostasis and tolerance. The safety profile of RTX reveals that most reactions are infusion related. In patients with autoimmune diseases the incidence of serious and severe side effects is low. Systemic infection still remains a major concern and may result in death.
21162883 [A clinical analysis of hemophagocytic syndrome in autoimmune diseases]. 2010 Oct OBJECTIVE: To analyze the clinical features of patients with hemophagocytic syndrome (HPS) in autoimmune diseases (AID). METHODS: We collected the data of 11 patients with AID complicated with HPS in Peking Union Medical College Hospital from 2004 to 2009. The underlying diseases, clinical features, laboratory findings and treatment outcomes were retrospectively analyzed. RESULTS: Of the 11 patients, 3 were male, 8 were female. Mean age was (30.7 ± 18.3) years. The underlying diseases included Still disease (n = 4), systemic lupus erythematosus(n = 3), and rheumatoid arthritis, primary Sjögren's syndrome, Wegener granulomatosis and Crohn disease in each one case. HPS was associated with the onset of AID (n = 4), active infection alone (n = 1) and both factors (n = 6). HPS was clinically characterized by high fever (100%), hepatosplenomegaly (72.7%), lymphadenopathy (63.3%) and central nervous system involvement (36.3%). 4 patients presented with disseminated intravascular coagulation (DIC) (36.3%). Laboratory data mainly manifested with cytopenia (100%), liver dysfunction (100%), hypofibrinogenemia (62.5%), hypertriglyceridemia (81.8%), serum ferritin > 500 µg/L (100%), low NK-cell activity (80%) and hemophagocytosis in bone marrow (100%). Based on treating underlying infections and use of corticosteroids and immunosuppressive agents in combination with intravenous immunoglobulins (IVIG) therapy, 5 patients recovered, 6 patients died. The mortality rate was 54.5%. DIC were associated with mortality (r = 0.69, P = 0.019). CONCLUSION: The episode of HPS always occurs simultaneously with multiple system involvement that was often difficult to distinguish from active AID. The present of DIC on HPS related with poor prognosis and high mortality. Corticosteroids and immunodepressant and IVIG may improve the prognosis of HPS, while anti-infection therapy is very important and necessary for the patients accompany with active infection.
20963181 Autoimmunity in Coxsackievirus B3 induced myocarditis: role of estrogen in suppressing aut 2010 May 1 Picornaviruses are small, non-enveloped, single stranded, positive sense RNA viruses which cause multiple diseases including myocarditis/dilated cardiomyopathy, type 1 diabetes, encephalitis, myositis, orchitis and hepatitis. Although picornaviruses directly kill cells, tissue injury primarily results from autoimmunity to self antigens. Viruses induce autoimmunity by: aborting deletion of self-reactive T cells during T cell ontogeny; reversing anergy of peripheral autoimmune T cells; eliminating T regulatory cells; stimulating self-reactive T cells through antigenic mimicry or cryptic epitopes; and acting as an adjuvant for self molecules released during virus infection. Most autoimmune diseases (SLE, rheumatoid arthritis, Grave's disease) predominate in females, but diseases associated with picornavirus infections predominate in males. T regulatory cells are activated in infected females because of the combined effects of estrogen and innate immunity.
20930460 Induction of pulmonary fibrosis by methotrexate treatment in mice lung in vivo and in vitr 2010 Oct Methotrexate (MTX) has been used as the first-line disease-modifying antirheumatic drug (DMARD) in patients with early progressive rheumatoid arthritis (RA). Several severe side effects such as myelosuppression, hepato-, nephro-, and pulmonary toxicities have been reported. However, the pathogenic mechanism of MTX-induced pulmonary fibrosis is still unknown. Here, we evaluated the morphological and biological changes of the pulmonary fibrosis in mice treated with MTX. Three, four and five weeks after consecutive administration of MTX (3 mg/kg/day), hydroxyproline content in the lung tissues increased significantly to about 2 times higher that of the control level. This result closely reflected to the results of hematoxylin and eosin (HE) and Azan stains. Immunohistochemical analysis revealed that MTX treatment resulted in a decrease of alveolar epithelial cells and an increase of fibroblast cells in the mouse lung tissues. When we examined the effects of MTX on primary mouse alveolar epithelial cell (MAEC) and mouse lung fibroblast (MLF) survival in vitro, the efficiency of MTX-induced cytotoxicity and apoptosis in MAEC was more sensitive than MLF cells. Thus, our results indicate that the administration of MTX by an oral route could induce a fibrotic response with cell dysfunction of the alveolar epithelium by which MTX-induced apoptosis. Our results thus suggest that MTX could induce alveolar epithelial cell injury and resulted in the loss of integrity of the alveolar-capillary barrier basement membranes followed by the recruitment and proliferation of myofibroblasts with the deposition of collagens.
20799760 Ketoprofen pharmacokinetics, efficacy, and tolerability in pediatric patients. 2010 Oct 1 The NSAID ketoprofen is used widely in the management of inflammatory and musculoskeletal conditions, pain, and fever in children and adults. Pharmacokinetic studies show that drug exposure after a single intravenous dose is similar in children and adults (after dose normalization), and thus similar mg/kg bodyweight dosing may be used in children and adults. Ketoprofen crosses the blood-brain barrier and therefore has the potential to cause central analgesic effects. Ketoprofen has been investigated in children for the treatment of pain and fever, peri- and postoperative pain, and inflammatory pain conditions. The results of four clinical trials in febrile conditions with the oral syrup formulation indicate that ketoprofen is as effective as acetaminophen (paracetamol) and ibuprofen, allowing children to rapidly return to daily activities with improvements in sleep quality and appetite. Studies of ketoprofen in the management of postoperative pain indicate that ketoprofen is a highly effective analgesic when administered perioperatively for a variety of surgical types, by a variety of routes, and whether given preoperatively or postoperatively. For adenoidectomy, intravenous ketoprofen provided superior postoperative analgesic efficacy compared with placebo. Analgesic efficacy was similar with intravenous, intramuscular, or rectal routes of administration, but oral administration just before surgery was inferior to intravenous administration in this setting. In patients undergoing a tonsillectomy, intravenous ketoprofen was superior to intravenous tramadol in terms of the need for postoperative rescue analgesia, but did not remove the need for rescue opioid therapy in these patients. Intravenous ketoprofen had superior postoperative analgesic efficacy to placebo when given as an adjuvant to epidural sufentanil analgesia after major surgery. Oral ketoprofen has shown efficacy in the treatment of juvenile rheumatoid arthritis. Ketoprofen is generally well tolerated in pediatric patients. Most of the adverse events reported are mild and transient, and are similar to those observed with other NSAIDs. Long-term tolerability has not yet been fully established in children, but data from three studies in >900 children indicate that oral ketoprofen is well tolerated when administered for up to 3 weeks after surgery. In conclusion, ketoprofen is effective and well tolerated in children for the control of post-surgical pain and for the control of pain and fever in inflammatory conditions.
20720563 Generation of antibodies of distinct subclasses and specificity is linked to H2s in an act 2011 Jan Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disease, characterized by antibodies to type VII collagen (COL7). EBA can be induced in mice by immunization with a fragment of the non-collagenous 1 domain of murine COL7. Contrary to other autoimmune diseases, e.g., rheumatoid arthritis, little is known about the genetic susceptibility for EBA. We therefore used the EBA mouse model to address the hypothesis that disease induction depends on the major histocompatibility complex (MHC) haplotype. Mice from different inbred strains were immunized with recombinant murine COL7. Five distinct responses were observed: induction of (i) severe disease in SJL/J (H2s) and female MRL/MpJ (H2k), (ii) mild and transient disease in C57Bl/10.s (H2s), (iii) microscopic blistering in DBA/1J (H2q), (iv) only presence of non-pathogenic autoantibodies in C57Bl/6J (H2b), NZM2410/J (H2z), BXD2 (H2b), and male MRL/MpJ, and (v) complete resistance to EBA in NOD/ShiLtJ (H2g7) and C57Bl/10.q (H2q) mice. Overall, susceptibility to EBA was strongly associated with H2s. In addition, the diseased phenotype was associated with autoantibodies to specific regions of COL7. Our findings show that induction of antibodies with a distinct specificity is linked to the MHC haplotype in experimental EBA. Furthermore, our data are the basis for future studies with the goal of identifying non-MHC EBA susceptibility genes.
20718866 Catalytic digestion of human tumor necrosis factor-α by antibody heavy chain. 2010 Sep It has long been an important task to prepare a catalytic antibody capable of digesting a targeting crucial protein that controls specific life functions. Tumor necrosis factor-α (TNF-α) is a cytokine and an important molecule concerned with autoimmune diseases such as rheumatoid arthritis, chronic obstructive pulmonary disease, and Crohn's disease. A mAb (ETNF-6 mAb) raised against human TNF-α was prepared, and the steric conformation was created by using molecular modeling after the cDNA was sequenced. The heavy chain (ETNF-6-H) of the mAb was considered to possess a catalytic triad-like structure in the complementarity determining regions (CDRs). As a result, ETNF-6-H exhibited a peptidase and a protease activity. In fact, ETNF-6-H predominantly cleaved the Ser5-Arg6 bond of TNF-α at the first step, resulting in the generation of a fragment of ∼ 17 kDa. This fragment was digested to a smaller molecule of 15 kDa by scission of the Gln21-Ala22 bond. The intermediate product was further converted into a fragment of 13.3 kDa by successive cleavage of the Leu36-Leu37 and Asn39-Gly40 bonds. The heavy chain possessed a protease activity against TNF-α with a multicleavage site.
20460064 Review of 107 hallux MTP joint arthrodesis using dome-shaped reamers and a stainless-steel 2010 May BACKGROUND: The purpose of this study was to retrospectively review the results of patients treated with hallux MTP joint arthrodesis using dome-shaped reamers for joint preparation and a precontoured dorsal stainless steel plate for internal fixation. MATERIALS AND METHODS: A series of 145 patients (155 feet) were identified. Postoperative evaluation included weightbearing radiographs, physical examination, and chart review. Outcomes were assessed with a pain visual analog scale, AOFAS hallux score, as well as a detailed questionnaire and a subjective satisfaction survey. RESULTS: Ninety-eight patients (107 feet) met the criteria for the study. The mean followup was 61 weeks. Revision cases accounted for 18.7% (20/107). Rheumatoid arthritis (RA) was present in 32.7% (35/107). The average postoperative AOFAS hallux score was 79.7 and pain VAS was 19. The average pre- and postoperative hallux valgus angle was 26.5 and 12.3 degrees, respectively (p < 0.05). Eighty-nine of 107 patients (83.1%) reported good to excellent results at final followup. Discomfort related to prominence of the plate occurred in 14.9% (16/107). The nonunion rate was 12.1% (13/107). The nonunion rate for patients with/without RA was 22.9% (8/35) and 6.9% (5/72), respectively (p < 0.05). Patients with a nonunion noted more hardware related pain than those with a union (p < 0.05). CONCLUSION: First MTP joint arthrodesis using this technique achieves a high union rate. RA patients have a lower union and higher complication rate.
20333761 Myth and reality: practical test system for the measurement of anti-DNA antibodies in the 2010 The myth persists that only the labor intensive Farr radioimmunoassay and Crithidia luciliae immunofluorescence (CL-IFA) are systemic lupus erythematosus (SLE)-specific tests. We compared them to ELISA with bacteriophage lambda DNA (EL-dsDNA) and denatured calf thymus DNA (EL-ssDNA). By percentile ranking, the specificity cut-off level was set both out of clinical context (SOCC) on 100 blood bank donors, and in clinical context (SICC) on 100 patients with either rheumatoid arthritis or scleroderma (50/50). Clinical sensitivity was calculated on 100 random SLE patients. At 95% SICC, the sensitivity of Farr, CL-IFA, EL-dsDNA, and EL-ssDNA was similar (95%CI): 76% (66-84), 76% (66-84), 63% (53-72), and 75% (65-83), respectively; 87% of the patients were positive by at least one method and 55%by all methods. At 99% SICC, the sensitivity was also similar (95% CI): 57% (47-67), 47% (37-57), 58% (47-67), and 43% (33-53), respectively. The areas under ROC curve were similar (95% CI) when patients were used as controls for specificity. At 99% SOCC, EL-ssDNA identified 89% positive, 2 negative but positive by another method at 95% SICC, and 9 negative (i.e. 89/2/9), followed by CL-IFA (80/6/14), Farr (76/12/12), and EL-dsDNA (64/23/13). Thus, at relatively low cost and easy automation, under the same conditions of specificity, the two ELISA tests combined were at least as good, if not superior, to CL-IFA or Farr: they showed similar clinical sensitivity and also identified more patients with anti-DNA antibodies.
20298123 Discrete changes in circulating regulatory T cells during infliximab treatment of Crohn's 2010 Jun Deficiency of CD4+CD25+ regulatory T cells (Tregs) may be involved in Crohn's disease (CD) pathogenesis. In rheumatoid arthritis (RA), the anti-TNF-alpha antibody infliximab increases circulating Treg numbers. We aimed to evaluate circulating Tregs in CD before and after infliximab therapy. In 20 patients with active CD, blood samples were obtained before infusion of infliximab 5 mg/kg and 1, 7, and 42 days after therapy. Clinical, biochemical, and fecal markers of inflammation were obtained. Nine healthy volunteers served as controls. We applied a novel Treg marker, the absence of CD127 expression, to identify Tregs by whole-blood flow cytometry. Treg percentages were similar among CD patients [median 7.7%, interquartile range (IQR) 5.3-10.1%] and healthy volunteers (median 7.6% IQR 6.3-8.9%) with discrete changes (median 7.3%, IQR 4.5-10.1%) throughout the study period, irrespective of the significant clinical effect of infliximab. Unlike in RA, we found no arising population of CD62L - Tregs; however, we observed a rapid recruitment of lymphocytes and upregulation of the intestinal homing marker alpha4beta7 integrin on CD4+T cells. In conclusion, our results do not support the hypothesis that the clinical effect of infliximab is mediated by a reinforcement of defective, circulating Tregs in CD.
20231207 Cytokine profiles of macrophage activation syndrome associated with rheumatic diseases. 2010 May OBJECTIVE: To elucidate the cytokine profiles of macrophage activation syndrome (MAS) in relation to underlying rheumatic diseases and prognosis. METHODS: The clinical features and laboratory data of 18 patients with MAS and rheumatic diseases were retrospectively analyzed. Serum levels of macrophage colony-stimulating factor (M-CSF), interleukin 18 (IL-18), tumor necrosis factor-alpha, interleukin 6, interferon-gamma, ferritin, and beta2-microglobulin (beta2m) were measured. These data were compared between underlying diseases and between those who died and those who recovered. RESULTS: Of the 18 patients with MAS, 9 had underlying systemic lupus erythematosus (SLE), 7 had adult-onset Still's disease (AOSD), 1 had rheumatoid arthritis (RA), and 1 had antiphospholipid syndrome. Three patients with SLE and 1 patient with RA died. The serum M-CSF and IL-18 levels were substantially elevated in all the patients. In the patients with SLE, the M-CSF level was higher than the IL-18 level (median: 4879 vs 1341 pg/ml, p = 0.0054), and it was the reverse in the patients with AOSD (5883 vs 228,350 pg/ml, p = 0.0017). The serum M-CSF and beta2m levels were significantly higher in the patients who died than in those who recovered (M-CSF: 18,245 vs 3404 pg/ml, p = 0.019; beta2m: 18.8 vs 5.4 mg/dl, p = 0.0058). CONCLUSION: The cytokine profiles associated with MAS differed between patients with SLE and patients with AOSD. The patients with SLE showed a prominent increase in serum M-CSF levels, as did the patients with AOSD in serum IL-18 level. Patients who died had higher serum M-CSF and ss(2)m levels, and this suggests that aggressive treatment for patients with MAS and these profiles should be promptly started.
20224922 MEFV gene mutations and its impact on the clinical course in ulcerative colitis patients. 2011 Jul Ulcerative colitis (UC) is an inflammatory disease of the colonic mucosa. The presence of gene responsible for FMF, MEFV, which frequently causes inflammation, may aggravate the clinical course of UC. We aimed to determine the prevalence of MEFV mutations in UC patients and its impact on the clinical course. Four groups were formed as group 1 UC with distal disease, group 2 UC with pancolonic disease, group 3 UC with total colectomy, and group 4 Rheumatoid Arthritis (RA) patients. Eleven mutations of FMF gene were investigated. The mean age of group 1, 2, 3, and 4 were 46.7 ± 13.9, 43.8 ± 12.9, 44.8 ± 14.2, and 45.8 ± 10.9 years, respectively. The mutations were identified in 19 of the 54 UC patients (35.2%). Homozygous E148Q in 2 patients (3.7%) and heterozygous in 17 patients (31.5%) (E148Q 11.1%, M694V 5.6%, V726A 5.6%, K695R 1.8%, M680I 1.8%, and compound heterozygous 5.6%) were determined. Frequencies of MEFV mutations in group 1, 2, and 3 were 30, 27.3, and 58.3%, respectively. The mutations were identified in 3 of the 20 RA patients (15%). All of them were heterozygous. The rate of MEFV mutations were higher in group 3 than in group 4 (P = 0.018), and the number of attacks that were treated with steroid in all UC patients with mutation positive was higher than in mutation negative (P = 0.016). FMF gene mutations may be identified in UC patients up to 58.3%. It may be suggested that the UC patients with severe form should be identified for MEFV mutations before the judgment of colectomy.
20210371 Current status of vascular endothelial growth factor inhibition in age-related macular deg 2010 Jun Angiogenesis, the process by which new vessels are created from pre-existing vasculature, has become the subject of intense research in recent years. Increased rates of angiogenesis are associated with several disease states, including cancer, age-related macular degeneration (AMD), psoriasis, rheumatoid arthritis, and diabetic retinopathy. Vascular endothelial growth factor (VEGF) is an important modulator of angiogenesis, and has been implicated in the pathology of a number of conditions, including AMD, diabetic retinopathy, and cancer. AMD is a progressive disease of the macula and the third major cause of blindness worldwide. If not treated appropriately, AMD can progress to involve both eyes. Until recently, the treatment options for AMD have been limited, with photodynamic therapy (PDT) the mainstay of treatment. Although PDT is effective at slowing disease progression, it rarely results in improved vision. Several therapies have been or are now being developed for neovascular AMD, with the goal of inhibiting VEGF. These VEGF inhibitors include the RNA aptamer pegaptanib, partial and full-length antibodies ranibizumab and bevacizumab, the VEGF receptor decoy aflibercept, small interfering RNA-based therapies bevasiranib and AGN 211745, sirolimus, and tyrosine kinase inhibitors, including vatalanib, pazopanib, TG 100801, TG 101095, AG 013958, and AL 39324. At present, established therapies have met with great success in reducing the vision loss associated with neovascular AMD, whereas those still under investigation offer the potential for further advances. In AMD patients, these therapies slow the rate of vision loss and in some cases increase visual acuity. Although VEGF-inhibitor therapies are a milestone in the treatment of these disease states, several concerns need to be addressed before their impact can be fully realized.
20181653 Interplay between CD45RA+ regulatory T cells and TNF-alpha in the regulation of human Th17 2010 Apr The balance between effector CD4(+) T cells secreting IL-17 (T(h)17) and regulatory T cells (Treg) plays an important role in autoimmune disorders that include rheumatoid arthritis (RA) and Crohn's disease. Tumor necrosis factor (TNF)-alpha is a key pro-inflammatory cytokine that contributes to disease pathogenesis. We investigated the interplay between CD45RA(+) Treg and TNF-alpha in the regulation of human T(h)17 differentiation. We found that CD45RA(+) Treg promoted while TNF-alpha inhibited naive CD4(+) T-cell differentiation into IL-17 and CCL20 co-expressing T(h)17 cells without influencing their IL-22 release. Unexpectedly, CD45RA(+) Treg depletion abrogated TNF-alpha suppressive function. Finally, dendritic cell-derived TNF-alpha suppressed the development of IL-17(+)CCL20(+) expressing T(h)17 cells. In conclusion, CD45RA(+) Treg positively governs human T(h)17 development, which is impaired by TNF-alpha. We propose that TNF-alpha may represent a negative feedback mechanism to control IL-17/CCL20- but not IL-22-associated autoimmune pathologies.
19939283 Foot posture influences the electromyographic activity of selected lower limb muscles duri 2009 Nov 26 BACKGROUND: Some studies have found that flat-arched foot posture is related to altered lower limb muscle function compared to normal- or high-arched feet. However, the results from these studies were based on highly selected populations such as those with rheumatoid arthritis. Therefore, the objective of this study was to compare lower limb muscle function of normal and flat-arched feet in people without pain or disease. METHODS: Sixty adults aged 18 to 47 years were recruited to this study. Of these, 30 had normal-arched feet (15 male and 15 female) and 30 had flat-arched feet (15 male and 15 female). Foot posture was classified using two clinical measurements (the arch index and navicular height) and four skeletal alignment measurements from weightbearing foot x-rays. Intramuscular fine-wire electrodes were inserted into tibialis posterior and peroneus longus under ultrasound guidance, and surface EMG activity was recorded from tibialis anterior and medial gastrocnemius while participants walked barefoot at their self-selected comfortable walking speed. Time of peak amplitude, peak and root mean square (RMS) amplitude were assessed from stance phase EMG data. Independent samples t-tests were performed to assess for significant differences between the normal- and flat-arched foot posture groups. RESULTS: During contact phase, the flat-arched group exhibited increased activity of tibialis anterior (peak amplitude; 65 versus 46% of maximum voluntary isometric contraction) and decreased activity of peroneus longus (peak amplitude; 24 versus 37% of maximum voluntary isometric contraction). During midstance/propulsion, the flat-arched group exhibited increased activity of tibialis posterior (peak amplitude; 86 versus 60% of maximum voluntary isometric contraction) and decreased activity of peroneus longus (RMS amplitude; 25 versus 39% of maximum voluntary isometric contraction). Effect sizes for these significant findings ranged from 0.48 to 1.3, representing moderate to large differences in muscle activity between normal-arched and flat-arched feet. CONCLUSION: Differences in muscle activity in people with flat-arched feet may reflect neuromuscular compensation to reduce overload of the medial longitudinal arch. Further research is required to determine whether these differences in muscle function are associated with injury.