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ID PMID Title PublicationDate abstract
17237445 Phosphorylated ERM is responsible for increased T cell polarization, adhesion, and migrati 2007 Feb 1 Systemic lupus erythematosus (SLE) is an autoimmune/inflammatory disease characterized by autoantibody production and abnormal T cells that infiltrate tissues through not well-known mechanisms. We report that SLE T lymphocytes display increased levels of CD44, ezrin, radixin, and moesin (ERM) phosphorylation, stronger actin polymerization, higher polar cap formation, and enhanced adhesion and chemotactic migration compared with T cells from patients with rheumatoid arthritis and normal individuals. Silencing of CD44 by CD44 small interfering RNA in SLE T cells inhibited significantly their ability to adhere and migrate as did treatment with Rho kinase and actin polymerization inhibitors. Forced expression of T567D-ezrin, a phosphorylation-mimic form, enhanced remarkably the adhesion and migration rate of normal T cells. Anti-CD3/TCR autoantibodies present in SLE sera caused increased ERM phosphorylation, adhesion, and migration in normal T cells. pERM and CD44 are highly expressed in T cells infiltrating in the kidneys of patients with lupus nephritis. These data prove that increased ERM phosphorylation represents a key molecular abnormality that guides T cell adhesion and migration in SLE patients.
17910335 Intrapartum anaphylaxis to penicillin in a woman with rheumatoid arthritis who had no prio 2007 Sep BACKGROUND: Little is known about the development of drug allergy during pregnancy or in patients with altered immune status. OBJECTIVE: To report a case of new-onset penicillin allergy during pregnancy in a woman with rheumatoid arthritis. METHODS: A 39-year-old woman with rheumatoid arthritis developed intrapartum anaphylaxis that led to fetal demise. She had previously received penicillin-based antibiotics without any allergic reactions. Because of group B streptococcus colonization, an intravenous infusion of penicillin G was started during labor. Within minutes, she developed severe anaphylaxis. RESULTS: A fluorescent enzyme immunoassay revealed a moderate level of specific IgE to penicilloyl G and penicilloyl V (3.15 kU/L and 2.77 kU/L, respectively). Given the patient's history, these positive results were considered confirmatory of penicillin allergy. This case raises a number of salient points. First, patients can develop severe allergy to penicillin despite having safely received penicillins in the past. Possible factors that influenced the development of severe penicillin sensitivity in this patient are discussed. Second, unexpected intrapartum anaphylaxis can occur, which can be life threatening to the mother or fetus. Third, safe and reliable methods for diagnosis of drug allergy must be available. CONCLUSIONS: This case illustrates that during the current unavailability of skin testing reagents in the United States, a positive result on in vitro testing can be helpful in confirming penicillin allergy in cases in which drug challenge is deemed unsafe.
17949547 Synovial lymphoid neogenetic factors in Behçet's synovitis: do they play a role in self-l 2007 Jul OBJECTIVE: Lymphoid neogenesis seems to play an important role in the persistence of chronic inflammation and has been shown in various disorders characterized by chronic inflammation including rheumatoid arthritis. Arthritis of Behçet's disease is characterized by non-erosive arthritis in which the disease course is considered to be subacute and self limiting. However, molecular mechanisms underlying those features of Behçet's arthritis have not been defined yet. In order to determine the contribution of lymphoid neogenesis in the disease course of Behçet's arthritis, we investigated the synovial fluid (SF) levels of CXCL 12, CXCL 13, CCL 21 homeostatic chemokines and the percentage of SF naive lymphocytes expressing their receptors such as CXCR4+ and CCR7+. We further measured the SF TGF-Beta and INF-Beta levels which are known to contribute lymphoid neogenesis via leading persistent expression of CXCR4 on T cells and inhibiting T cell apoptosis, respectively. METHODS: Fifty-one [15 BD, 17 RA, and 19 osteoarthritis (OA)] patients with at least one- sided knee arthritis were enrolled in the study. Patients with BD constituted the study group, and RA, OA patients were used as positive and negative control groups, respectively. The SF levels of CXCL 12, CXCL 13, CCL 21, TGF-Beta and INF-Beta were measured by ELISA. CXCR4, CCR7 chemokine receptors on SF lymphocytes were tested by Flow- cytometry. Kruskal-Wallis test and Mann-Whitney U test were used for statistical analysis where appropriate. RESULTS: Synovial fluid CCL 21 levels were found to be increased in RA patients as compared to BD and OA patients (p = 0.003, and p = 0.013, respectively). No significant difference was detected between BD and OA patients with respect to CCL 21 levels. Both CXCL 12 and CXCL 13 SF levels were found to be higher in RA and BD patients as compared to OA patients (CXCL-12; p = 0.012, and p = 0.024), (CXCL 13; p < 0.001, and p = 0.007). However, no difference with regard to SF levels of both CXCL 12 and CXCL 13 were found between RA and BD patients. Percentages of both CD3+CXCR4+ lymphocytes and CD3+CCR7+ lymphocytes in the SF of RA patients were detected to be increased as compared to those of BD and OA patients (CD3+CXCR4+; p = 0.019, p = 0.048, respectively), (CD3+CCR7+; p = 0.023, p = 0.001, respectively). However, no differences with respect to the percentages of SF lymphocytes expressing CD3+CXCR4+ or CD3+CCR7+ were found between BD and OA patients. Both TGF-Beta and INF-Beta SF levels were found to be higher in RA patients as compared to BD and OA patients (TGF-Beta; p = 0.041, and p = 0.003), (INF-Beta; p = 0.012, and p = 0.016). However, no differences with regard to SF levels of both TGF-Beta and INF-Beta were found between BD and OA patients. CONCLUSION: Considering the subacute, self limiting and non-erosive course of arthritis observed in BD, our finding of detection of lower levels of CCL21 and TGF-Beta1 and IFN-Beta in BD patients, seems to prevent the development of LN and chronic inflammation in Behçet's synovitis. In support of this view, percentages of SF naïve T lymphocytes were found to be lower in BD patients comparing with those of the RA. Absence of tertiary lymphoid structures in BD patients, may explain the spontaneous resolution of Behçet's arthritis in most of the cases.
17227914 T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th ce 2007 Jan 22 This report shows that highly self-reactive T cells produced in mice as a result of genetically altered thymic T cell selection spontaneously differentiate into interleukin (IL)-17-secreting CD4+ helper T (Th) cells (Th17 cells), which mediate an autoimmune arthritis that clinically and immunologically resembles rheumatoid arthritis (RA). The thymus-produced self-reactive T cells, which become activated in the periphery via recognition of major histocompatibility complex/self-peptide complexes, stimulate antigen-presenting cells (APCs) to secrete IL-6. APC-derived IL-6, together with T cell-derived IL-6, drives naive self-reactive T cells to differentiate into arthritogenic Th17 cells. Deficiency of either IL-17 or IL-6 completely inhibits arthritis development, whereas interferon (IFN)-gamma deficiency exacerbates it. The generation, differentiation, and persistence of arthritogenic Th17 cells per se are, however, insufficient for producing overt autoimmune arthritis. Yet overt disease is precipitated by further expansion and activation of autoimmune Th17 cells, for example, via IFN-gamma deficiency, homeostatic proliferation, or stimulation of innate immunity by microbial products. Thus, a genetically determined T cell self-reactivity forms a cytokine milieu that facilitates preferential differentiation of self-reactive T cells into Th17 cells. Extrinsic or intrinsic stimuli further expand these cells, thereby triggering autoimmune disease. Intervention in these events at cellular and molecular levels is useful to treat and prevent autoimmune disease, in particular RA.
17461530 Intra-synovial ropivacaine and morphine for pain relief after total knee arthroplasty: a p 2007 Apr 30 PURPOSE: Several analgesic techniques are available for pain management after a major operation. MATERIALS AND METHODS: From December 2005 to February 2006, a prospective, double-blind study was performed involving 90 patients who had undergone a total knee arthroplasty. Patients were randomly divided into three equal groups (n=30). Demographic data, including age, height, weight, knee score, visual analogue scale (VAS), and range of flexion were evaluated preoperatively. Before wound closure, patients were given intra-synovial injections of the following solutions: patients in group I received 40mL of 300mg ropivacaine with 1:200,000 epinephrine and 5mg morphine; patients in Group II received 40mL of 300mg ropivacaine with epinephrine; and patients in Group III received 50mL normal saline as a control. All patients received an epidural patient-controlled analgesia (PCA) for 24 postoperative hours. Analgesic efficacy was evaluated using the VAS at intervals of 2, 4, 6, 12, 24, 32, 40, and 48 hours postoperatively. During this period, the side effects, the dosage of rescue analgesia required, and the range of knee flexion were recorded for each group. RESULTS: There were no significant differences among the three groups with regards to the VAS and the required dose of rescue analgesia (p > 0.05). None of the groups demonstrated significant differences in the range of knee flexion and the incidence of postoperative nausea and emesis (p > 0.05). CONCLUSION: Therefore, we found that ropivacaine, alone or with morphine, injected into the synovial tissue, along with an epidural PCA has no additional benefits in pain control after a total knee arthroplasty.
17981265 Amygdala volume in patients receiving chronic corticosteroid therapy. 2008 Apr 1 BACKGROUND: Hippocampal volume reduction and declarative memory deficits are reported in humans and animals exposed to exogenous corticosteroids. The amygdala is another brain structure involved in the stress response that has important interactions with the hypothalamic-pituitary-adrenal axis. To our knowledge, no studies in animals or humans have examined the impact of exogenous corticosteroid administration on the amygdala. We assessed amygdala volume in patients receiving chronic prescription corticosteroid therapy and control subjects with similar medical histories not receiving corticosteroids. METHODS: Fifteen patients on long-term prednisone therapy and 13 control subjects of similar age, gender, ethnicity, education, height, and medical history were assessed with magnetic resonance imaging. Amygdala volume was manually traced and compared between groups using a two-way analysis of variance (ANOVA). Correlations between amygdala volume, age, and corticosteroid dose/duration were assessed using Pearson's correlation coefficient. RESULTS: Compared with control subjects, corticosteroid-treated patients had significantly smaller amygdala volumes. Right amygdala volume correlated significantly with age in control subjects and with duration of corticosteroid therapy in patients. CONCLUSIONS: Patients receiving chronic corticosteroid therapy had smaller amygdala volumes than control subjects that correlated with duration of corticosteroid therapy. These findings suggest that corticosteroid exposure may be associated with changes in the amygdala as well as hippocampus.
16311048 Interleukin-17, a regulator of angiogenic factor release by synovial fibroblasts. 2006 Apr OBJECTIVE: Angiogenesis is a process stimulated in inflamed synovium of patients with osteoarthritis (OA), and contributes to the progression of the disease. Synovial fibroblasts secrete angiogenic factors, such as vascular endothelial growth factor (VEGF), an up-regulator of angiogenesis, and this ability is increased by interleukin (IL)-1beta. The purpose of this study was to verify whether IL-17 contributes and/or synergizes with IL-1beta and tumor necrosis factor (TNF)-alpha in vessel development in articular tissues by stimulating the secretion of proangiogenic factors by synovial fibroblasts. DESIGN: We stimulated in vitro synovial fibroblasts isolated from OA, rheumatoid arthritis (RA) and fractured patients (FP) with IL-17 and IL-1beta and from OA patients with IL-17, IL-1beta and TNF-alpha. In the supernatants from the cultures, we assayed the amount of VEGF by immunoassay and other angiogenic factors (keratinocyte growth factor, KGF; hepatocyte growth factor, HGF; heparin-binding endothelial growth factor, HB-EGF; angiopoietin-2, Ang-2; platelet-derived growth factor B, PDGF-BB; thrombopoietin, TPO) by chemiluminescence; semiquantitative RT-PCR was used to state mRNA expression of nonreleased angiogenic factors (Ang-2 and PDGF-BB) and tissue inhibitors of metalloproteinase (TIMP)-1. RESULTS: IL-17, TNF-alpha and IL-1beta increased VEGF secretion by synovial fibroblasts from OA patients. IL-17 and IL-1beta also increased VEGF secretion in RA and FP. Besides, IL-17 increased KGF and HGF secretions in OA, RA and FP; in OA and RA, IL-17 also increased the HB-EGF secretion and the expression of TIMP-1 as protein and mRNA. In OA patients IL-17 had an additive effect on TNF-alpha-stimulated VEGF secretion. CONCLUSIONS: These results suggest that IL-17 is an in vitro stimulator of angiogenic factor release, both by its own action and by cooperating with TNF-alpha.
16755652 Trichostatin A cooperates with Fas-mediated signal to induce apoptosis in rheumatoid arthr 2006 Jun OBJECTIVE: To clarify the effects of trichostatin A (TSA), a histone deacetylase inhibitor, on the growth and survival of rheumatoid arthritis synovial fibroblasts (RA-SF). METHODS: Cell viability was assessed using a WST-8 assay and direct cell counting. Apoptosis was detected by annexin V staining on a flow cytometer. Protein and mRNA expression was determined by Western blotting, flow cytometry, and RT-PCR. RESULTS: TSA suppressed cell growth of RA-SF in a dose-dependent manner, as determined by WST-8 assay and direct cell counting. Other histone deacetylase inhibitors also showed inhibitory effects on RA-SF proliferation. TSA upregulated p21(WAF1/CIP1) cell cycle inhibitor, suggesting that cell cycle arrest is involved in the reduction of cell numbers. In addition, TSA cooperated with Fas-induced pathway to induce cell death, determined by WST-8 assay and annexin V staining. TSA reduced FLICE inhibitory protein (FLIP) expression but not Bcl-2, Bcl-XL, and Fas expression, indicating that the synergistic effect may be through downregulation of FLIP. CONCLUSION: TSA has antirheumatic effects on RA-SF and might be a potential therapeutic tool for the treatment of RA.
19029827 Disease phenocode analysis identifies SNP-guided microRNA maps (MirMaps) associated with h 2008 Dec Recently we reported the results of a genome-wide disease phenocode analysis interrogating the relationships between structural features and gene expression patterns of disease-linked SNPs, microRNAs and mRNAs of protein-coding genes in association to phenotypes of 15 common human disorders (Cell Cycle 2008;7:2570-83; 3564-76). One of the main implications of this analysis is that transcriptionally co-regulated SNP sequence-bearing RNAs are more likely to exert a cumulative effect in trans on phenotypes. In this work, we test the validity of a disease phenocode concept within a genomic context of distinct continuously spaced sets of disease-linked SNPs and mRNAs of relevant proteincoding genes. We report a sequence homology profiling of two sets of disease-linked SNPs which are located within continuous genomic regions associated with individual protein-coding genetic loci (NLRP1 and STAT4) and are likely to exhibit common profiles of transcriptional activity. Most of microRNAs (15 of 19; 79%) homologous to the NLPRP1-associated disease-linked SNPs have potential protein-coding mRNA targets among the principal components of the nuclear import pathway (NIP) and/or inflammasome pathways, including KPNA1, NLRP1 and NLRP3 genes. We demonstrate that estimates of cumulative targeting effects of microRNAs on mRNAs within distinct allelic contexts of disease-linked SNPs are in agreement with microarray analysis-defined gene expression phenotypes associated with human genotypes of Crohn's disease (CD) and rheumatoid arthritis (RA) populations. Microarray experiments and disease phenocode analysis identify ten-gene expression signatures which seem to reflect the activated status of disease-linked SNPs/microRNAs/mRNAs axis in peripheral blood mononuclear cells (PBMC) of 66% CD patients and 80% RA patients. Comparisons of ten-gene signature expression profiles and NLRP3/NLRP1 mRNA expression ratios in PBMC of individual CD and RA patients and control subjects indicate that measurements of these markers may be useful for diagnostic applications. Our findings demonstrate that NLPRP1- and STAT4-associated disease-linked SNPs have common sequence-defined features which are recapitulating the essential phenotype-affecting features of genome-wide disease-linked SNPs, suggesting that NLRP1 (NALP1) and STAT4 genetic loci may constitute "master" disease genes. We conclude that both genome-wide SNP variations and SNP polymorphisms associated with "master" disease genes may cause similar genetically-defined malfunctions of the NIP and inflammasome/innate immunity pathways which are likely to contribute to pathogenesis of multiple common human disorders.
19138249 Hydroxychloroquine-induced hyperpigmentation: a case report. 2008 Dec The antimalarials are one of the most commonly prescribed drugs in medical practice, for conditions such as rheumatoid arthritis as well as malaria. They are generally well-tolerated and the possible side effects of synthetic antimalarials, though infrequent, are well known. Besides the familiar adverse reactions, a localized mucocutaneous bluish-grey to black discolouration can sometimes be seen with antimalarial drugs. The aim of this report was to draw attention to the localized mucocutaneous bluish-grey hyperpigmentation induced by hydroxychloroquine with a case presentation and a review of the literature.
17437420 Increased serum high mobility group box-1 level in Churg-Strauss syndrome. 2007 May Churg-Strauss syndrome (CSS) is a rare form of systemic vasculitis occurring in patients with asthma and hypereosinophilia; however, its mechanisms involved in the severe tissue inflammation with vasculitis are poorly understood. High mobility group box 1 (HMGB1) protein, originally identified as a DNA binding protein, also has potent pro-inflammatory and proangiogenic properties. In this study, we hypothesized that HMGB1 might be associated with CSS, and examined serum HMGB1 levels and compared those of asthma patients and healthy volunteers. We also investigated HMGB1 expression in the lesion, and eosinophil HMGB1 amount in CSS patients. We found that the serum HMGB1 levels in CSS patients were significantly higher than those of asthma patients and healthy volunteers. Eosinophils in the CSS lesion expressed HMGB1 and HMGB1 level in eosinophils from CSS patients was significantly higher than that of asthma patients, while there was no significant difference in HMGB1 levels in peripheral mononuclear cells. The serum HMGB1 level in CSS patients decreased after the steroid therapy, and showed significant positive correlations with several molecules, including soluble interleukin-2 receptor, soluble thrombomodulin, and eosinophil cationic protein in sera. We propose that HMGB1 might contribute to the pathogenesis of CSS.
17384176 Compared clinical efficacy and bone metabolic effects of low-dose deflazacort and methyl p 2007 Jun OBJECTIVE: To evaluate: (i) a correct equivalence ratio of clinical efficacy between low-dose deflazacort (DFZ) and methyl prednisolone (MP); and (ii) bone metabolic effects of low-dose DFZ and MP in the treatment of male RA and PsA. METHODS: A total of 21 male patients with active RA or PsA, naive to steroid treatment were chosen for the study. Group I: 10 patients treated for 6 months with DFZ 7.5 mg, calcium, cholecalciferol and a DMARD; for the following 6 months with MP 4 mg, calcium, cholecalciferol and a DMARD. Group II: 11 patients treated for 6 months with MP 4 mg, calcium, cholecalciferol and a DMARD; for the following 6 months with DFZ 7.5 mg, calcium, cholecalciferol and a DMARD. At day 0, 90, 180, 240 and 360 evaluation of ACR improvement criteria; a blood sample for total and bone-specific ALP, calcium, phosphorus, PTH, SHBG, estradiol, ACTH, osteocalcin, LH, OPG; a sample of urine for calcium, phosphorus, creatinine and DPD. RESULTS: 13/21 patients (6/10 Group I; 7/11 Group II) reached ACR 20 at 6 months; 14/21 (7/10 Group I, 7/10 Group II) at 12 months. Only at the third month we observed in Group II vs Group I a reduction of OPG (24% vs 6%, P = n.s.); ALP (P < 0.001) and osteocalcin (P = 0.006) decreased in both groups from the third month; DPD decreased in both groups only from the sixth month (P = 0.002). CONCLUSIONS: The correct equivalence ratio of DFZ to MP is 1.875:1, and of DFZ to prednisolone 1.5:1. We found a relative prevalence of bone resorption compared to bone formation in the first 6 months of treatment. The trend of OPG requires further investigation.
18208824 Evaluation of latent tuberculosis infection in patients with inflammatory arthropathies be 2008 Feb OBJECTIVE: To compare the efficacy of the conventional skin test and a novel flow cytometric whole blood assay in the diagnosis of latent tuberculosis infection (LTBI) in patients with rheumatological diseases evaluated for treatment with TNF-alpha-blocking agents. METHODS: Prospective study of 97 consecutively enrolled patients, who were assessed for the presence of LTBI through clinical history, Mendel-Mantoux skin testing and chest X-ray. In addition, T-cell reactivity towards tuberculin (PPD, purified protein derivative) and the Mycobacterium tuberculosis-specific proteins ESAT-6 and CFP-10 was determined ex vivo using a flow cytometric whole blood assay. RESULTS: After standard screening, 15% of patients receiving TNF-alpha-blocking therapy were pretreated with isoniazide (INH), another 5% of patients did not receive TNF-alpha-blocking therapy because of LTBI. PPD-reactivity in the skin was observed in 14% of patients compared with 39% with the whole blood test. Analysis of the M. tuberculosis-specific response to ESAT-6 and CFP-10 revealed positive results in 16% of patients. Using a decision tree incorporating history, chest X-ray and either skin-test or ESAT-6/CFP-10 results, 18 or 22% of the patients, respectively, were classified as latently infected with M. tuberculosis. Four patients treated with INH because of a positive skin reaction did not show reactivity to ESAT-6/CFP-10 in the whole blood assays. Another six patients not pretreated with INH because of negative skin tests would have received INH, had the results of the whole blood assay been taken into account. CONCLUSION: The Mendel-Mantoux skin test has a low sensitivity and specificity for the diagnosis of LTBI in this cohort of patients, potentially resulting in both over- and under-treatment with prophylactic INH when compared with the flow cytometric analysis of whole blood T-cell reactivity to proteins specific to M. tuberculosis. Use of T-cell based in vitro tests may help to refine diagnostic testing for LTBI.
16729287 Anti-interleukin-6 receptor antibody therapy favors adrenal androgen secretion in patients 2006 Jun OBJECTIVE: Proinflammatory cytokines such as tumor necrosis factor (TNF) were demonstrated to inhibit adrenal steroidogenesis in patients with rheumatoid arthritis (RA), and this was particularly evident in the increase in adrenal androgen levels during anti-TNF therapy. This study investigated the influence on steroidogenesis of an interleukin-6 (IL-6)-neutralizing strategy using IL-6 receptor monoclonal antibodies (referred to as MRA). METHODS: In a placebo-controlled, double-blind, randomized study over 12 weeks in 29 patients with RA being treated with prednisolone, 13 of whom received placebo and 16 of whom received 8 mg MRA/kg body weight, the effects of MRA on serum levels of adrenocorticotropic hormone (ACTH), cortisol, 17-hydroxyprogesterone (17OHP), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione (ASD), estrone, and 17beta-estradiol, as well as their respective molar ratios, were determined. RESULTS: MRA therapy markedly improved clinical signs of inflammation (the erythrocyte sedimentation rate, swollen joint score, and Disease Activity Score in 28 joints). Serum levels of ACTH and cortisol and the molar ratio of cortisol to ACTH did not change. Although serum levels of DHEA and DHEAS remained stable during therapy, the DHEAS:DHEA molar ratio significantly decreased in treated patients (P = 0.048). Serum levels of ASD as well as the ASD:cortisol and ASD:17OHP molar ratios increased in MRA-treated patients (minimum P < 0.004). Serum levels of estrone and 17beta-estradiol did not change. but the estrone:ASD molar ratio (an indicator of aromatization) decreased during 12 weeks of MRA treatment (P = 0.001). CONCLUSION: Neutralization of IL-6 increases secretion of biologically active adrenal androgens in relation to that of precursor hormones and estrogens. This is another important indication that proinflammatory cytokines interfere with adrenal androgen steroidogenesis in patients with RA.
17363330 Cell surface CCR5 density determines the intensity of T cell migration towards rheumatoid 2007 May As we have recently shown that the number of CCR5 molecules at the cell surface determines the efficiency of its function as a chemokine receptor, we tested the hypothesis that cell surface CCR5 density could influence the intensity of T lymphocyte recruitment into the rheumatoid joint. For this purpose, we established two Jurkat cell line-derived clones that differed only by their cell surface CCR5 densities. We studied their chemotaxis towards TNF-alpha-transduced rheumatoid synoviocytes supernatant. The Jurkat cell subline that expressed the higher cell surface CCR5 density migrated more intensively towards the supernatant of TNF-alpha-transduced synoviocytes than the Jurkat cell subline that expressed a lower surface CCR5 density. Moreover, this migration was blocked by an anti-CCR5 mAb. The CCR5 density on T cell surface, which is constant over time for a given individual, but varies drastically from one individual to another, might thus be a factor determining the intensity of joint inflammation in the course of RA.
16688603 Parkinsonism in Caplan's syndrome. 2006 Apr Parkinsonism is a rare feature of immunological diseases. We describe a 67-year-old man with Caplan's syndrome (CS) and parkinsonism. CS is an immunologic disease characterised by the presence of rheumatoid arthritis associated with a specific form of pneumoconiosis. Parkinsonism as a manifestation of involvement of the central nervous system in this condition has never been reported. Following immunosuppressive treatment both the CS and the parkinsonian signs and symptoms showed a marked improvement. The role of immune mechanisms in these parkinsonian syndromes is discussed.
17228322 Activation-induced upregulation of inhibitory killer Ig-like receptors is regulated by pro 2007 Apr Inhibitory killer Ig-like receptor (KIR) expression was upregulated by protein kinase C (PKC) activation in stable Jurkat clones that express KIR or CD8KIR fusion proteins. PKC-induced KIR upregulation was mediated by the cytoplasmic tail of KIR and regulated at the post-transcriptional level. PKC inhibition, metabolic labeling and colocalization studies demonstrated that the activation of the conventional PKCs upregulated surface and cellular KIR levels by stimulating the maturation processes in endoplasmic reticulum-Golgi and by promoting the recycling of surface KIR through sorting endosomes. Similar studies also revealed that KIR was secreted to plasma membrane through lytic granules in a PKCdelta-dependent manner. Consequently, PKCdelta inhibition caused the formation of giant perinuclear granules, which trapped KIR and FasL as well as CPE and Lamp1.
17986350 Flexor Hallucis Longus tendon rupture in RA-patients is associated with MTP 1 damage and p 2007 Nov 6 BACKGROUND: To assess the prevalence of and relation between rupture or tenosynovitis of the Flexor Hallucis Longus (FHL) tendon and range of motion, deformities and joint damage of the forefoot in RA patients with foot complaints. METHODS: Thirty RA patients with painful feet were analysed, their feet were examined clinically for the presence of pes planus and range of motion (ROM), radiographs were scored looking for the presence of forefoot damage, and ultrasound examination was performed, examining the presence of tenosyovitis or rupture of the FHL at the level of the medial malleolus. The correlation between the presence or absence of the FHL and ROM, forefoot damage and pes planus was calculated. RESULTS: In 11/60(18%) of the feet, a rupture of the FHL was found. This was associated with a limited motion of the MTP1-joint, measured on the JAM (chi2 = 10.4, p = 0.034), a higher prevalence of pes planus (chi2 = 5.77, p = 0.016) and a higher prevalence of erosions proximal at the MTP-1 joint (chi2 = 12.3, p = 0.016), and joint space narrowing of the MTP1 joint (chi2 = 12.7, p = 0.013). CONCLUSION: Rupture of the flexor hallucis longus tendon in RA-patients is associated with limited range of hallux motion, more erosions and joint space narrowing of the MTP-1-joint, as well as with pes planus.
17227824 Parapharyngeal abscess in a patient receiving etanercept. 2007 Feb OBJECTIVE: To report a case of parapharyngeal abscess associated with Streptococcus viridans in a patient with rheumatoid arthritis receiving treatment with etanercept. CASE SUMMARY: A 40-year-old man diagnosed with rheumatoid arthritis had received treatment with nonsteroidal antiinflammatory drugs, methotrexate, and deflazacort. Six months prior to admission, the patient had a Disease Activity Score of 3.4; clinicians decided to start treatment with etanercept. Chest X-rays were normal and the tuberculin skin test was negative. Treatment with etanercept plus methotrexate was started. Three months later, methotrexate was discontinued. Six months after etanercept therapy was started, the patient presented to our emergency department with a swelling of his neck, odynophagia, otalgia, and trismus. The clinical course was consistent with parapharyngeal abscess. Etanercept treatment was suspended. The parapharyngeal abscess was drained and intravenous methylprednisolone, amoxicillin/clavulanic acid, and clindamycin were administered. The parapharyngeal abscess secretion culture was positive for S. viridans and Bacteroides spp. The patient's condition improved with antibiotic therapy; he was discharged 5 days after admission. DISCUSSION: Tumor necrosis factor-alpha plays an essential role in the immune-mediated response to infection. In our patient, the most possible cause of parapharyngeal abscess was considered to be etanercept because of the temporal relationship between exposure to the drug and onset of symptoms. Etanercept was the only drug administered before the abscess developed. Based on the Naranjo probability scale, an association between etanercept and the adverse reaction could be considered possible. CONCLUSIONS: Patients initiated on etanercept therapy should be closely monitored for the development of tuberculosis and other infections. During treatment, all febrile or novel illnesses should be evaluated promptly. If clinical evaluation leads to the suspicion of tuberculosis and other infections associated with etanercept, it should be discontinued immediately.
19092289 Prevalence of interrelated autoantibodies in thyroid diseases and autoimmune disorders. 2008 Oct OBJECTIVE: We determined the autoantibody profile in autoimmune thyroid diseases (AITD) and examined the distribution of thyroid-related autoantibodies in other autoimmune disorders. METHODS: We tested sera from 234 patients with Graves' disease (GD), 130 with Hashimoto's thyroiditis (HT), 249 with other autoimmune diseases, and 50 healthy controls by enzyme-linked immunosorbent assay or radioimmunoassay. RESULTS: Autoantibodies except TSH receptor antibody (Ab), anti-thyroglobulin (Tg) Ab and anti-thyroid peroxidase (TPO) Ab were not significantly prevalent in patients with AITD despite a significantly high elevation of thyroid-related Ab. Significant prevalence of autoantibodies related to AITD was observed in type 1 diabetes patients. Elevation of anti-Tg Ab was seen in patients with primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH), and anti-TPO Ab was elevated in patients with PBC. Although the prevalence of anti-acetylcholine receptor Ab and systemic lupus erythematosus (SLE)- related Ab was significant in AIH, primary Sjögren's syndrome (pSS)-related Ab were also found in both liver diseases. In myasthenia gravis (MG) patients, thyroid-related Ab and pSS-related Ab were detected in both MG groups, although SLE-related Ab were limited to the anti-muscle specific kinase Ab-positive MG patients. In patients with connective tissue diseases, anti- Tg Ab and anti-TPO Ab were significantly prevalent. CONCLUSION: Thyroid-related Ab were significantly elevated in all autoimmune diseases. Conversely, the elevations of Ab were not significant in the patients with AITD, suggesting a close relationship between AITD and other immune-mediated diseases.