Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
16816069 Plasma and tissue expression of the long pentraxin 3 during normal pregnancy and preeclamp 2006 Jul OBJECTIVE: Cell death normally occurs during pregnancy and is critical during its common complication, preeclampsia. The long pentraxin 3 (PTX3) gene is generated in tissues that cope with excessive or deregulated cell death and inhibits the cross-presentation of cell-associated antigens. We examined whether PTX3 is expressed during pregnancy and possibly involved in the development of preeclampsia. METHODS: Women with preeclampsia (n = 30), women with uncomplicated pregnancies (n = 66), age-matched healthy women (n = 50), women who developed acute bacterial infections (n = 20), and women with rheumatoid arthritis (n = 20) were studied. The concentrations of PTX3 were measured in the blood by a sandwich enzyme-linked immunosorbent assay (ELISA) and in placentas by immunohistochemistry. The concentrations of PTX3 and C-reactive protein in the various groups were compared by nonparametric tests (the Mann-Whitney U and the Kruskal-Wallis tests). The odds of developing preeclampsia were assessed using logistic regression. RESULTS: PTX3 was expressed in amniotic epithelium and chorionic mesoderm, trophoblast terminal villi, and perivascular stroma in placentas from pregnancies of uncomplicated subjects. Circulating levels steadily rose during normal gestation and peaked during labor. Serum levels of PTX3 were strikingly higher in preeclampsia compared with normal control pregnancies (5.08 +/- 1.34 and 0.59 +/- 0.07 ng/mL, respectively, P < .001). Sites of higher expression in the placentas from preeclamptic patients include infarcts and fibrinoid zones. CONCLUSION: Defects in the homeostatic response to cell death/remodeling events, revealed by enhanced levels of PTX3, could be implicated in preeclampsia. LEVEL OF EVIDENCE: II-2.
17415429 Stimulatory effect of fragments from transcribed region of ribosomal repeat on human perip 2006 Oct Fragments from the transcribed region of the ribosomal repeat include considerable amounts of unmethylated CpG DNA motifs. These motifs activate immune cells via the interaction with Toll receptors. In vitro experiments confirmed the stimulatory effect of transcribed region of ribosomal repeat on human lymphocytes. Culturing of lymphocytes in a medium containing 2-20,000 ng/ml fragments from transcribed region of ribosomal repeat was accompanied by structural changes in the nucleus in a considerable number of cells. These changes manifested in translocation of pericentromeric heterochromatin from the membrane to the center of the nucleus and activation of the nucleolus and were accompanied by a significant increase in interleukin-6 production and slight stimulation of tumor necrosis factor-a synthesis. The transcribed region of the ribosomal repeat and E. coli DNA had various effects on quantitative parameters of lymphocytes. Our results suggest the existence of mechanisms of stimulation not mediated by the interaction of CpG DNA motifs with Toll receptors.
18350329 An open-label pilot study of the effectiveness of adalimumab in patients with rheumatoid a 2008 Aug This prospective open-label pilot study evaluated the effectiveness and safety of adalimumab and the relationship to antibodies against infliximab (IFX) in adult patients with active rheumatoid arthritis (RA) who had been treated previously with IFX and experienced treatment failure owing to lack or loss of response or intolerance. Patients self-administered adalimumab 40 mg subcutaneously every other week for 16 weeks, followed by maintenance therapy for up to Week 56. Measures of effectiveness included American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria, 28-joint Disease Activity Score, and the Health Assessment Questionnaire Disability Index. Serum IFX concentrations, human antichimeric antibody against IFX (HACA), adalimumab serum concentrations, antiadalimumab antibody, and safety also were assessed. Of the 41 enrolled patients, 37 completed 16 weeks and 30 completed 56 weeks of treatment. Patients experienced clinically meaningful improvements in all measures of RA activity, with greater response rates observed for patients who had experienced loss of initial response to or intolerance of IFX. At Week 16, 46% of patients achieved an ACR20 and 28% achieved an ACR50; 61% achieved an at least moderate and 17% achieved a good EULAR response. Clinical benefit was maintained through Week 56 in all effectiveness parameters. Baseline HACA status did not significantly impact effectiveness. No new safety signals were observed; neither former IFX intolerance status nor baseline HACA status had a clinically relevant impact on adverse event frequency or severity. Adalimumab was effective and well-tolerated in patients with RA who previously failed IFX therapy, irrespective of reason for discontinuation and of HACA status.
16906380 Infectious myositis involving the piriformis in a patient with rheumatoid arthritis. 2006 A 49-year-old Japanese woman treated with oral corticosteroids, methotrexate, and infliximab for malignant rheumatoid arthritis was admitted because of fever and low back pain. The white blood cell count and C-reactive protein concentration were elevated. Lumbar and pelvic computed tomography showed enlargement of the piriformis muscle including a hypodense area consistent with gas formation. The patient was treated successfully for infectious myositis with intravenous antibiotics.
17430516 Disseminated mucormycosis and orbital ischaemia in combination immunosuppression with a tu 2007 Apr Disseminated mucormycosis, with pulmonary and cerebral angioinvasive disease, developed in a 65-year-old woman with rheumatoid arthritis being treated with combination immunosuppression including adalimumab. Clinical presentation included progressive orbital ischaemia. To the best of the authors' knowledge, this is the first reported case of disseminated mucormycosis in a patient treated with a tumour necrosis factor inhibitor. Important pathophysiological factors are considered.
16188943 Effect of age on prevalence of anticitrullinated protein/peptide antibodies in polyarticul 2006 Feb OBJECTIVES: Anticitrullinated protein/peptide antibodies (ACPA) have an excellent diagnostic performance for rheumatoid arthritis (RA). Despite similarities between RA and polyarticular juvenile idiopathic arthritis (JIA), the prevalence of ACPA in polyarticular JIA is low. We wanted to evaluate the influence of age, disease duration and total immunoglobulin G (IgG) concentration on ACPA positivity in this cohort. METHODS: Patients with JIA were classified according to age and International League of Associations for Rheumatology classification. Sixty-one JIA patients aged less than 16 yr were included and classified as polyarticular JIA (poly JIA <16; n=23) or non-polyarticular JIA (n=38). In addition, a group of 21 polyarticular JIA patients, aged more than 16 yr (poly JIA >16) and a group of 51 RA patients were included. Antibodies to the synthetic citrullinated peptides pepA and pepB were detected by line immunoassay and antibodies to cyclic citrullinated peptides (CCP2) by enzyme-linked immunosorbent assay. Serum IgG was measured by fixed-time immunonephelometry. RESULTS: No ACPA reactivity was observed in the non-polyarticular group. In poly JIA <16, only 1/23 had anti-CCP2 antibody, whereas in poly JIA >16 patients a significantly higher fraction was detected (6/21). All but one of the anti-CCP2 reactive patients were rheumatoid factor (RF) positive. Assessing anti-CCP2 antibody concentration as a continuous variable, significantly higher titres were found in poly JIA >16 compared with poly JIA <16. No correlation between anti-CCP2 concentration and total IgG was detected. Four patients demonstrated immunoreactivity against pepA and pepB; all of them were anti-CCP2 reactive, poly JIA >16 patients. CONCLUSIONS: ACPA are present in low prevalence in polyarticular JIA and are particularly found in the RF-positive subset. With age, a significant increase in anti-CCP2 positivity is observed in polyarticular JIA patients.
19026700 Interleukin-1RN gene polymorphisms in elderly patients with rheumatic inflammatory chronic 2009 Jan The objective of this study was to investigate whether there is an association between IL1RN polymorphism and disease susceptibility for three age-related inflammatory conditions: polymyalgia rheumatica (PMR), giant cell arteritis (GCA), and elderly-onset rheumatoid arthritis (EORA). A tandem-repeat polymorphism within IL1RN intron 2 was analyzed in 139 PMR, 69 GCA, and 156 RA patients (75 with EORA) as well as in 437 healthy subjects, together with the in vitro production of IL-1beta. Our results showed that the IL1RN*2/2 genotype was more frequent in PMR patients compared with controls (p = 0.032, odds ratio = 1.785, 95% confidence interval = 1.047-3.044) and GCA patients (p = 0.008, odds ratio = 4.661, 95% confidence interval = 1.352-16.065). We found no difference in the distribution of genotypes between PMR and EORA or between EORA and controls. However, the frequency of the IL-1RN*2/2 genotype had a tendency to be higher in patients with EORA compared with young onset RA. The presence of IL1RN*1 or IL1RN*2 allele was not associated with severity of the disease in PMR and GCA patients and did not influence the production of IL-1beta. In conclusion, the IL1RN*2 polymorphism in a homozygous state was associated with an increased susceptibility to PMR and may give some clues for a differential therapy with GCA.
19050894 A case of Poncet's disease (tuberculous rheumatism). 2009 Jul We describe a 37-year-old woman with recurrent polyarthritis, and recurrent erythema nodosum on the flexible side of her left forearm. On an X-ray of the chest, infiltration of the right upper lobe was observed. Transcription-reverse transcription concerted reaction in sputum samples revealed Mycobacterium tuberculosis (M. tuberculosis). Resolution of the polyarthritis with anti-tuberculosis (TB) drugs occurred in 3 days. We diagnosed her with Poncet's disease (PD). PD is considered to be a reactive arthritis, which is a different entity from tuberculous arthritis. Although PD is a rare disease, we should be aware of it as one of the differential diagnoses, even in patients without typical symptoms of TB.
18277670 [Clinical comparative studies on effect of tranexamic acid on blood loss associated with t 2007 Dec OBJECTIVE: To investigate an effect of tranexamic acid on blood loss associated with total knee arthroplasty (TKA). METHODS: From June 2005 to June 2006, 102 patients (43 males, 59 females; aged 59-77 years, averaged 68 years) underwent TKA. Of the 102 patients, 59 had osteoarthritis, 23 had rheumatoid arthritis, and 20 had traumatic arthritis. The illness course ranged from 2 to 12 years. They were randomized divided into Group A and Group B of 51 patients each. The patients in Group A received tranexamic acid, and the patients in Group B received an equal volume of normal saline. In Group A, 1 g of tranexamic acid dissolved in 250 ml of normal saline was intravenously infused before deflation of the tourniquet; another intravenous administration of the same drug of the same dosage was given 3 hours later. In Group B, only 250 ml of normal saline was infused intravenously. The amounts of blood loss and blood transfusion during operation and after operation in all the 102 patients were recorded. They were also observed for whether they had deep vein thrombosis. D-dimeride, fibrinogen, prothrombin time, and activated partial thromboplastin time were also examined before operation, during operation (deflation of the tourniquet), and 3 hours after operation. RESULTS: The blood loss was 256 +/- 149 ml in Group A and 306 +/- 214 ml in Group B during operation; there was no significant difference between the two groups (P > 0.05). The postoperative drainage volume was 478 +/- 172 ml in Group A and 814 +/- 156 ml in Group B, and the total blood loss was 559 +/- 159 ml in Group A and 1208 +/- 243 ml in Group B; there were significant differences between the two groups (P < 0.05). The averaged amount of blood transfusion was 556 +/- 174 ml in Group A and 1024 +/- 278 ml in Group B; there was a significant difference between the two groups (P < 0. 05). The postoperative hemoglobin concentration was higher in Group A than that in Group B (1.0-1.1 g/dL vs. 0.6-0.8 g/dL). The postoperative follow-up for 6-12 months revealed that no deep vein thrombosis was found in both lower limbs of the patients by the color Doppler ultrasonography. The level of D-dimeride was significantly higher 3 hours after operation than before operation (0.92 +/- 0.56 mg/L vs. 0.35 +/- 0.13 mg/L in Group A; 1.32 +/- 0.79 mg/L vs. 0.37 +/- 0.21 mg/L in Group B) (P < 0.05). The D-dimeride level 3 hours after operation was significantly higher in Group B than in Group A (P < 0.05). There were no significant differences in the levels of fibrinogen, prothrombin time,.and activated partial thromboplastin time between the two groups (P > 0.05). CONCLUSION: During and after the TKA operation, a short-term use of tranexamic acid can significantly decrease blood loss and blood transfusion with no increasing risk for venous thrombosis.
19022821 Interleukin 21 as a target of intervention in autoimmune disease. 2008 Dec Interleukin 21 (IL21) belongs to a family of cytokines that bind to a composite receptor consisting of a private receptor (IL21R) and the common cytokine receptor gamma chain (gamma(C)). The IL21R is widely distributed on lympho-haematopoietic cells and IL21 impacts a number of cell types, including CD8+ memory T cells, NK cells and subsets of CD4 memory T cells. One essential role of IL21 is the promotion of B-cell activation and differentiation or death during humoral immune responses. Increased IL21 production is characteristic of certain autoimmune diseases and is likely to contribute to autoantibody production as well as pathological features of autoimmune disease. The critical role of IL21 in promoting humoral immune responses makes it an important focus of potential therapeutic interventions in conditions characterised by overproduction of pathogenic autoantibodies.
18975321 Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis. 2008 Nov OBJECTIVE: There is evidence supporting a therapeutic range for methotrexate polyglutamate (MTXGlu) concentrations in the treatment of rheumatoid arthritis (RA). Knowledge of the pharmacokinetics of MTXGlu1-5 is required for optimal timing of blood sampling. The aim of this study was to determine the time to steady state and the half-life of accumulation of red blood cell (RBC) MTXGlu1-5 in patients with RA commencing oral MTX, and the time for RBC MTXGlu1-5 to become undetectable and the half-life of elimination of RBC MTXGlu1-5 in patients ceasing treatment with oral MTX. METHODS: Ten patients beginning treatment and 10 patients stopping treatment with low-dose oral MTX were recruited. Blood samples were initially collected weekly, with gradual extension to monthly collection over the study period. RBC MTXGlu1-5 concentrations were assayed by high-performance liquid chromatography. Results were analyzed using a first-order exponential method. RESULTS: The median times to reach steady state in RBCs (defined as 90% of the maximum concentration) were 6.2, 10.6, 41.2, 149, and 139.8 weeks, respectively, for MTXGlu1, MTXGlu2, MTXGlu3, MTXGlu4, and MTXGlu5. The median half-life of accumulation for RBC MTXGlu1-5 ranged from 1.9 weeks to 45.2 weeks. The median times for MTXGlus to become undetectable in RBCs were 4.5, 5.5, 10, 6, and 4 weeks, respectively, for MTXGlu1, MTXGlu2, MTXGlu3, MTXGlu4, and MTXGlu5. The median half-life of elimination for RBC MTXGlu1-5 ranged from 1.2 weeks to 4.3 weeks. CONCLUSION: There is wide interpatient variability of RBC MTXGlu1-5 accumulation and elimination in adults with RA. These data also suggest that after a dose change, >6 months are required for RBC MTXGlu1-5 to reach steady state. Such delays in achieving steady state suggest that more rapid dose escalation or subcutaneous administration from the outset should be considered.
17478472 The efficacy of inhibiting tumour necrosis factor alpha and interleukin 1 in patients with 2007 Jul OBJECTIVE: New treatments that inhibit the cytokines tumour necrosis factor alpha (TNFalpha) and interleukin 1 (IL-1) in the treatment of rheumatoid arthritis have proven clinical effect against placebo and methotrexate (MTX) in several clinical trials in early and late-stage disease and different severity groups. Since there are no head-to-head randomized controlled trials directly comparing the currently available treatments, etanercept, adalimumab, infliximab or anakinra, we perform a meta-analysis that adjusts for differences between study characteristics, and allows indirect comparisons between treatments. METHODS: Thirteen trials of cytokine antagonists were included from a systematic review of the literature. They reported the primary outcome of American College of Rheumatology (ACR) response criteria at 6 months or beyond. Meta-analytical methods are used to quantify relative treatment effects, using the log odds ratio of an ACR20 or ACR50 response at 6 months, whilst adjusting for study-level variables. RESULTS: In each of the trials, cytokine treatment was efficacious in comparison with placebo or MTX. For each treatment, the inclusion of MTX in combination improved the response. After adjustment for study-level variables, we found TNFalpha antagonists to be more efficacious compared with anakinra (P < 0.05). Indirect comparisons between the three TNFalpha antagonists indicated no difference in efficacy. Sensitivity analysis using a different statistical model structure confirmed these results. CONCLUSION: When the outcome of interest is the probability of an ACR20 or ACR50 response at 6 months we found: (i) treatment with the IL-1 antagonist anakinra is better than placebo; (ii) for each treatment, the use of combination MTX improves the probability of response; (iii) treatment with any of the TNFalpha antagonists is better than with the IL-1 antagonist anakinra; and (iv) all drugs in the TNFalpha antagonist class are no different from each other.
16385520 The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination t 2006 Jan OBJECTIVE: To compare the efficacy and safety of adalimumab plus methotrexate (MTX) versus MTX monotherapy or adalimumab monotherapy in patients with early, aggressive rheumatoid arthritis (RA) who had not previously received MTX treatment. METHODS: This was a 2-year, multicenter, double-blind, active comparator-controlled study of 799 RA patients with active disease of < 3 years' duration who had never been treated with MTX. Treatments included adalimumab 40 mg subcutaneously every other week plus oral MTX, adalimumab 40 mg subcutaneously every other week, or weekly oral MTX. Co-primary end points at year 1 were American College of Rheumatology 50% improvement (ACR50) and mean change from baseline in the modified total Sharp score. RESULTS: Combination therapy was superior to both MTX and adalimumab monotherapy in all outcomes measured. At year 1, more patients receiving combination therapy exhibited an ACR50 response (62%) than did patients who received MTX or adalimumab monotherapy (46% and 41%, respectively; both P < 0.001). Similar superiority of combination therapy was seen in ACR20, ACR70, and ACR90 response rates at 1 and 2 years. There was significantly less radiographic progression (P < or = 0.002) among patients in the combination treatment arm at both year 1 and year 2 (1.3 and 1.9 Sharp units, respectively) than in patients in the MTX arm (5.7 and 10.4 Sharp units) or the adalimumab arm (3.0 and 5.5 Sharp units). After 2 years of treatment, 49% of patients receiving combination therapy exhibited disease remission (28-joint Disease Activity Score <2.6), and 49% exhibited a major clinical response (ACR70 response for at least 6 continuous months), rates approximately twice those found among patients receiving either monotherapy. The adverse event profiles were comparable in all 3 groups. CONCLUSION: In this population of patients with early, aggressive RA, combination therapy with adalimumab plus MTX was significantly superior to either MTX alone or adalimumab alone in improving signs and symptoms of disease, inhibiting radiographic progression, and effecting clinical remission.
17441664 Rheumatoid forefoot reconstruction: 1st metatarsophalangeal fusion and excision arthroplas 2007 Feb This is a retrospective review of 66 feet (mean follow-up of 3 years) in 43 patients with painful severe rheumatoid forefoot deformities. All were treated by arthrodesis of the first metatarsophalangeal (MTP) joint through a dorsomedial incision and excision of the lesser metatarsal heads through a separate plantar approach. The mean post-operative AOFAS scores were 65.94 (range: 32 to 82). The mean post-operative Foot Function Index (FFI) was 0.47 (range: 0.23 to 0.63). Eighty five percent (57/67 feet) reported excellent or good pain relief, improved cosmetic appearance, and improved footwear comfort. The mean hallux valgus angles improved from 39 degrees to 16 degrees and the intermetatarsal angle from 16 degrees to 8 degrees. Five feet had nonunion of the 1st MTP joint arthrodesis. There were five re-operations for non-union of the 1st MTP joint arthrodesis. The success of the operation as evidenced by this study depends upon attention to metatarsal length harmonisation, stabilisation of the 1st MTP joint and thereby even distribution of loading of the forefoot. The poor results in this study were as a result of a failure to secure the stability of the 1st MTP joint.
17223661 Predominant activation of MAP kinases and pro-destructive/pro-inflammatory features by TNF 2007 Aug OBJECTIVE: To examine the relative importance of tumour necrosis factor-receptor 1 (TNF-R1) and TNF-R2 and their signalling pathways for pro-inflammatory and pro-destructive features of early-passage synovial fibroblasts (SFB) from rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Cells were stimulated with tumour necrosis factor (TNF)alpha or agonistic anti-TNF-R1/TNF-R2 monoclonal antibodies. Phosphorylation of p38, ERK and JNK kinases was assessed by western blot; proliferation by bromodesoxyuridine incorporation; interleukin (IL)6, IL8, prostaglandin E(2) (PGE(2)) and matrix metalloproteinase (MMP)-1 secretion by ELISA; and MMP-3 secretion by western blot. Functional assays were performed with or without inhibition of p38 (SB203580), ERK (U0126) or JNK (SP600125). RESULTS: In RA- and OA-SFB, TNFalpha-induced phosphorylation of p38, ERK or JNK was exclusively mediated by TNF-R1. Reduction of proliferation and induction of IL6, IL8 and MMP-1 were solely mediated by TNF-R1, whereas PGE(2) and MMP-3 secretion was mediated by both TNF-Rs. In general, inhibition of ERK or JNK did not significantly alter the TNFalpha influence on these effector molecules. In contrast, inhibition of p38 reversed TNFalpha effects on proliferation and IL6/PGE(2) secretion (but not on IL8 and MMP-3 secretion). The above effects were comparable in RA- and OA-SFB, except that TNFalpha-induced MMP-1 secretion was reversed by p38 inhibition only in OA-SFB. CONCLUSION: In early-passage RA/OA-SFB, activation of MAPK cascades and pro-inflammatory/pro-destructive features by TNFalpha is predominantly mediated by TNF-R1 and, for proliferation and IL6/PGE(2) secretion, exclusively regulated by p38. Strikingly, RA-SFB are insensitive to p38 inhibition of MMP-1 secretion. This indicates a resistance of RA-SFB to the inhibition of pro-destructive functions and suggests underlying structural/functional alterations of the p38 pathway, which may contribute to the pathogenesis or therapeutic sensitivity of RA, or both.
19105984 CXCL10 and autoimmune diseases. 2009 Mar CXCL10 is a 10 kDa protein, which is categorized functionally as a Th1-chemokine. It binds to the receptor CXCR3 and regulates immune responses through the activation and recruitment of leukocytes, such as, T cells, eosinophils, and monocytes. Recent reports have shown that serum and/or tissue expressions of CXCL10 are increased in various autoimmune diseases like rheumatoid arthritis (RA), systemic lupus rythematosus (SLE), Sjogren syndrome (SS), systemic sclerosis (SSc), and idiopathic inflammatory myopathy (IIM). Moreover, CXCL10 and CXCR3 may have important roles in leukocyte homing to inflamed tissues and in the perpetuation of inflammation, and therefore, tissue damage. Our recent study shows that CXCL10 also has a pathogenic role in bone destruction via receptor activator of NF-kappaB ligand (RANKL) induction in inflamed synovial tissue of RA. In addition to its chemotactic effect, CXCL10 may have pleiotropic functions. Further research on the function of this chemokine and interactions between CXCL10 and other cytokines and chemokines may provide therapeutic targets in various autoimmune diseases.
18157932 Proteolysis of purified IgGs by human and bacterial enzymes in vitro and the detection of 2008 Apr A comparative in vitro survey of physiologically relevant human and microbial proteinases defined a number of enzymes that induced specific hinge domain cleavage in human IgG1. Several of these proteinases have been associated with tumor growth, inflammation, and infection. A majority of the identified proteinases converted IgG to F(ab')(2), and a consistent feature of their action was a transient accumulation of a single-cleaved intermediate (scIgG). The scIgG resulted from the relatively rapid cleavage of the first hinge domain heavy chain, followed by a slower cleavage of the second chain to separate the Fc domain from F(ab')(2). Major sites of enzymatic cleavage were identified or confirmed from the mass of the F(ab')(2) or Fab fragments and/or the amino-terminal amino acid sequence of the Fc for each enzyme including human matrix metalloproteinases (MMPs) 3 and 12, human cathepsin G, human neutrophil elastase (Fab), staphylococcal glutamyl endopeptidase I and streptococcal immunoglobulin-degrading enzyme (IdeS). The cleavage sites in IgG1 by MMP-3, cathepsin G and IdeS were used to guide the synthesis of peptide analogs containing the corresponding carboxy-termini to be used as immunogens in rabbits. Rabbit antibodies were successfully generated that showed selective binding to different human F(ab')(2)s and other hinge-cleavage fragments, but not to intact IgG. In Western blotting studies of synovial fluids from individuals with rheumatoid arthritis, the rabbit antibodies yielded patterns consistent with the presence of endogenous IgG fragments including F(ab')(2) and the single-cleaved IgG intermediate. The detection in synovial fluid of IgG fragments similar to those observed in the in vitro biochemical studies suggests that proteolysis of IgG may contribute to localized immune dysfunction in inflammatory environments.
16899925 Capillary blood viscosity in microcirculation. 2006 As known, at the arteriolar level there is the highest resistance to the flow due to the section and to the velocity with an average pressure fall of 50 mmHg (from 85 to 35 mmHg). This resistance is expressed in sec(-1) by the ratio W/2r. This ratio is very high with an average value of 332 sec(-1) and viscosity at this high shear-rate is negligible. At the capillary level the pressure fall is 11.5 mmHg but the vascular resistance W/2r is much lower, on average 32 sec(-1). We can say that if a resistance of 333 sec(-1) corresponds with a pressure fall of 50 mmHg, then a resistance of 32 sec(-1) should correspond with a pressure fall of 4.8 mmHg. The highest pressure fall is due to another kind of resistance which we can define as "Capillary Blood Viscosity" because it depends on the rheological and structural characteristics of the blood. Our instrument reproduces the structure of the capillary district in an experimental model and measures the General Blood Viscosity (GBV) and the Capillary Blood Viscosity (CBV) at the same shear-rate and in particular at the low shear-rate when in non-Newtonian fluids the highest increase in viscosity appears. Consequently, at the capillary, viscosity is dominant with respect to the other geometric and physical resistances. Moreover, the percentage ratio between the GBV and the CBV gives a physical measure of erythrocyte deformability. Knowing viscosity at shear-rate present in the circulatory system, we can obtain the size of RBCs aggregates in the different circulatory districts and their characteristics expressed like "aggregation bond". Changes in CBV are the only possibility in clinical practice to improve the circulatory flow in the capillary district because it is not sure that changes in the arteriolar section can improve the capillary flow or rather open arterio-venous anastomosis. Moreover, in the systemic circulation the aggregate size allows us to point out the phenomenon of cell adhesion because the presence of several receptors involves also the other blood cells. Finally the size and the stability of the RBCs aggregates can modify the endothelial thrombo-resistance.
16508967 Treatment of murine collagen-induced arthritis by the stress protein BiP via interleukin-4 2006 Mar OBJECTIVE: Following the demonstration that the stress protein, BiP, prevented induction of collagen-induced arthritis (CIA) in HLA-DRB*0101+/+ (HLA-DR1+/+) mice, we investigated the immunotherapeutic ability of BiP to suppress disease during the active phase of CIA in HLA-DR1+/+ and DBA/1 mice. METHODS: BiP was administered either subcutaneously or intravenously to DBA/1, HLA-DR1+/+, or interleukin-4 (IL-4)-knockout mice at the onset of arthritis. Immune cells were used in adoptive transfer studies or were restimulated in culture with BiP or type II collagen (CII). Proliferation and cytokine release were measured. In addition, serum anti-CII antibodies were measured by enzyme-linked immunosorbent assay. Disease progression was scored using a visual analog scale. RESULTS: BiP was successful in suppressing established CIA in HLA-DR1+/+ and DBA/1 mice. Serum levels of anticollagen IgG antibodies were reduced in BiP-treated mice. T cells from BiP-immunized mice produced Th2 cytokines, in particular, IL-4. Treatment with BiP was also shown to increase the production of CII-specific IL-5, IL-10, and interferon-gamma at the termination of the study. Development of severe CIA was prevented by the intravenous transfer of BiP-specific cells at the time of CIA induction in HLA-DR1+/+ mice or by transferring BiP-specific cells to DBA/1 mice at the onset of disease. BiP failed to ameliorate the development of CIA in IL-4-/-, HLA-DR1+/+ mice. CONCLUSION: These novel results show that BiP can suppress active CIA by the induction of regulatory cells that act predominantly via IL-4. Thus, BiP is a potential immunotherapeutic agent for the treatment of patients with rheumatoid arthritis.
16972811 The health effects of at-home written emotional disclosure in fibromyalgia: a randomized t 2006 Oct BACKGROUND: The presence and severity of the chronic pain syndrome fibromyalgia (FM) is associated with unresolved stress and emotional regulation difficulties. Written emotional disclosure is intended to reduce stress and may improve health of people with FM. PURPOSE: This study tests the effects of at-home, written emotional disclosure about stressful experiences on the health of people with FM and uses multiple follow-ups to track the time course of effects of disclosure. METHODS: Adults with FM (intention-to-treat, n=83; completers, n=72) were randomized to write for 4 days at home about either stressful experiences (disclosure group) or neutral time management (control group). Group differences in immediate mood effects and changes in health from baseline to 1-month and 3-month follow-ups were examined. RESULTS: Written disclosure led to an immediate increase in negative mood, which did not attenuate across the 4 writing days. Repeated-measures analyses from baseline to each follow-up point were conducted on both intention-to-treat and completer samples, which showed similar outcomes. At 1 month, disclosure led to few health benefits, but control writing led to less negative affect and more perceived support than did disclosure. At 3-month follow-up, these negative affect and social support effects disappeared, and written disclosure led to a greater reduction in global impact, poor sleep, health care utilization, and (marginally) physical disability than did control writing. Interpretation of these apparent benefits needs to be made cautiously, however, because the disclosure group had somewhat poorer health than controls at baseline and the control group showed some minor worsening over time. CONCLUSIONS: Written emotional disclosure can be conducted at home, and there is tentative evidence that disclosure benefits the health of people with FM. The benefits, however, may be delayed for several months after writing and may be of limited clinical significance.