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1.
Differentiation potential of CD14+ monocytes into myofibroblasts in patients with systemic sclerosis
Background
Circulating monocytes are a highly plastic and functionally heterogeneic cell type with an activated phenotype in patients with systemic sclerosis (SSc). CD14+ monocytes have the potential to differentiate into extra-cellular matrix (ECM) producing cells, possibly participating in fibrogenesis.Aim
To study the effect of GM-CSF, IL-4 and endothelin -1 (ET-1) alone or in combination on monocyte differentiation into myofibroblasts.Methods
CD14+ cells were isolated from peripheral blood from 14 SSc patients and healthy controls by positive selection and incubated with different combinations of GM-CSF, IL-4 and ET-1 for 14 days. Type-1 collagen and α-SMA were detected by Western blot, qPCR and confocal microscopy. HLA-DR, CD11c and CD14 expression was analysed by flow cytometry. A collagen gel contraction assay was performed for functional myofibroblast assessment.Results
GM-CSF both induced collagen and α-SMA expression after 14 days. ET-1 further increased GM-CSF-induced collagen expression in a dose dependent manner up to 30-fold. IL-4/GM-CSF combination leads to a more DC-like phenotype of monocytes associated with reduced collagen and α-SMA expression compared to GM-CSF alone. Collagen and α-SMA expression was higher in monocytes from SSc patients and monocytes were more prone to obtain a spindle form. In contrast to controls, ET-1 and IL-4 alone were sufficient to induce α-SMA expression in monocytes from SSc patients. Despite the induction of α-SMA expression, monocyte-derived myofibroblasts only had a moderate capability of contraction in functional analyses.Conclusion
SSc monocytes display increased maturation towards myofibroblasts demonstrated by their phenotype and α-SMA expression when compared to monocytes from healthy controls, however only with minor functional contraction properties. 相似文献2.
Antoine Fran?ois Emmanuel Chatelus Dominique Wachsmann Jean Sibilia Seiamak Bahram Ghada Alsaleh Jacques-Eric Gottenberg 《Arthritis research & therapy》2013,15(5):R168
Introduction
B lymphocytes might play a pathogenic role in dermal fibrosis in systemic sclerosis (SSc). B-cell activating factor (BAFF), a key cytokine for B-cell activation, is increased in the serum and the skin of patients with SSc. However, the ability of B cells directly to stimulate dermal fibroblasts and the role of BAFF are not fully understood. We therefore investigated the involvement of B cells and BAFF in the expression of collagen and profibrotic markers by dermal fibroblasts.Methods
Cocultures of blood B cells from healthy blood donors and normal or SSc dermal fibroblasts stimulated with anti-IgM and BAFF were performed. Alpha-SMA, TIMP1, MMP9, COL1A1, COL1A2, and COL3A1 mRNA expression were determined by quantitative RT-PCR. Soluble collagen, BAFF, IL-6, IL-1β, TGF-β1, and CCL2 protein secretion were assessed.Results
Coculture of blood B cells and dermal fibroblasts isolated from SSc patients induced IL-6, TGF-β1, CCL2, and collagen secretion, as well as Alpha-SMA, TIMP1, and MMP9 expression in dermal fibroblasts. Transwell assays demonstrated that this induction was dependent on cell-cell contact. Addition of anti-IgM and BAFF to the coculture increased IL-6, CCL2, TGF-β1, and collagen secretion. B cell- and BAFF-induced collagen secretion was highly reduced by anti-TGF-β1 antibodies.Conclusions
Our results showed for the first time a direct role of B cells on the production of collagen by dermal fibroblasts, which is further enhanced by BAFF. Thus, these results demonstrate a new pathogenic role of B cells and BAFF in fibrosis and systemic sclerosis. 相似文献3.
Hyun-Ja Jeong Sun-Young Nam Hyun-A Oh Na-Ra Han Young-Sick Kim Phil-Dong Moon Seung-Youp Shin Min-Ho Kim Hyung-Min Kim 《Arthritis research & therapy》2012,14(6):R259
Introduction
Interleukin (IL)-32 is an inflammatory cytokine induced by Mycobacterium tuberculosis and Mycobacterium bovis in a variety of cell types and discovered in the synovial of patients with rheumatoid arthritis (RA). Thymic stromal lymphopoietin (TSLP) play several roles in the pathogenesis of RA. However, the role of IL-32 and TSLP in RA has not been elucidated.Methods
We evaluated the specific mechanism of between IL-32 and TSLP in RA using human monocyte cell line, THP-1 cells.Results
Here we documented for the first time that IL-32 highly increased TSLP production in THP-1 cells and human blood monocytes. TSLP expression was induced by IL-32 via activation of caspase-1 and nuclear factor-κB. TSLP produced by IL-32 increased differentiation of monocytes but depletion of TSLP prevented differentiation of monocytes into macrophage-like cells. Chondroprotective drugs such as chondroitin sulfate (CS) and the traditional Korean medicine, BaekJeol-Tang (BT) decrease production of TSLP and activation of caspase-1 and nuclear factor-κB. In addition, CS and BT inhibited IL-32-induced monocytes differentiation.Conclusions
Taken together, IL-32 and TSLP are important cytokines involved in the development of RA. The effects of CS and BT were associated with the downregulation of TSLP and caspase-1 through negative regulation of IL-32 pathways in RA. 相似文献4.
Background
Chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1), belongs to the CC chemokine family that is associated with the disease status and outcomes of osteoarthritis (OA). Here, we investigated the intracellular signaling pathways involved in CCL2-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human OA synovial fibroblasts (OASFs).Methodology/Principal Findings
Stimulation of OASFs with CCL2 induced VCAM-1 expression. CCL2-mediated VCAM-1 expression was attenuated by CCR2 inhibitor (RS102895), PKCδ inhibitor (rottlerin), p38MAPK inhibitor (SB203580), and AP-1 inhibitors (curcumin and tanshinone IIA). Stimulation of cells with CCL2 increased PKCδ and p38MAPK activation. Treatment of OASFs with CCL2 also increased the c-Jun phosphorylation and c-Jun binding to the AP-1 element on the VCAM-1 promoter. Moreover, CCL2-mediated CCR2, PKCδ, p38MAPK, and AP-1 pathway promoted the adhesion of monocytes to the OASFs monolayer.Conclusions/Significance
Our results suggest that CCL2 increases VCAM-1 expression in human OASFs via the CCR2, PKCδ, p38MAPK, c-Jun, and AP-1 signaling pathway. The CCL2-induced VCAM-1 expression promoted monocytes adhesion to human OASFs. 相似文献5.
Gabriele Valentini Serena Vettori Giovanna Cuomo Michele Iudici Virginia D'Abrosca Domenico Capocotta Gianmattia Del Genio Carlo Santoriello Domenico Cozzolino 《Arthritis research & therapy》2012,14(4):R188
Introduction
We investigated early systemic sclerosis (SSc) (that is, Raynaud''s phenomenon with SSc marker autoantibodies and/or typical capillaroscopic findings and no manifestations other than puffy fingers or arthritis) versus undifferentiated connective tissue disease (UCTD) to identify predictors of short-term disease evolution.Methods
Thirty-nine early SSc and 37 UCTD patients were investigated. At baseline, all patients underwent clinical evaluation, B-mode echocardiography, lung function tests and esophageal manometry to detect preclinical alterations of internal organs, and were re-assessed every year. Twenty-one early SSc and 24 UCTD patients, and 25 controls were also investigated for serum endothelial, T-cell and fibroblast activation markers.Results
At baseline, 48.7% of early SSc and 37.8% of UCTD patients had at least one preclinical functional alteration (P > 0.05). Ninety-two percent of early SSc patients developed manifestations consistent with definite SSc (that is, skin sclerosis, digital ulcers/scars, two or more teleangectasias, clinically visible nailfold capillaries, cutaneous calcinosis, X-ray bibasilar lung fibrosis, X-ray esophageal dysmotility, ECG signs of myocardial fibrosis and laboratory signs of renal crisis) within five years versus 17.1% of UCTD patients (X2 = 12.26; P = 0.0005). Avascular areas (HR = 4.39 95% CI 1.18 to 16.3; P = 0.02), increased levels of soluble IL-2 receptor alpha (HR = 4.39; 95% CI 1.03 to 18.6; P = 0.03), and of procollagen III aminopropeptide predicted disease evolution (HR = 4.55; 95% CI 1.18 to 17; P = 0.04).Conclusion
Most early SSc but only a few UCTD patients progress to definite SSc within a short-term follow-up. Measurement of circulating markers of T-cell and fibroblast activation might serve to identify early SSc patients who are more likely to develop features of definite SSc. 相似文献6.
Sengupta K Alluri KV Satish AR Mishra S Golakoti T Sarma KV Dey D Raychaudhuri SP 《Arthritis research & therapy》2008,10(4):R85
Introduction
5-Loxin® is a novel Boswellia serrata extract enriched with 30% 3-O-acetyl-11-keto-beta-boswellic acid (AKBA), which exhibits potential anti-inflammatory properties by inhibiting the 5-lipoxygenase enzyme. A 90-day, double-blind, randomized, placebo-controlled study was conducted to evaluate the efficacy and safety of 5-Loxin® in the treatment of osteoarthritis (OA) of the knee.Methods
Seventy-five OA patients were included in the study. The patients received either 100 mg (n = 25) or 250 mg (n = 25) of 5-Loxin® daily or a placebo (n = 25) for 90 days. Each patient was evaluated for pain and physical functions by using the standard tools (visual analog scale, Lequesne''s Functional Index, and Western Ontario and McMaster Universities Osteoarthritis Index) at the baseline (day 0), and at days 7, 30, 60 and 90. Additionally, the cartilage degrading enzyme matrix metalloproteinase-3 was also evaluated in synovial fluid from OA patients. Measurement of a battery of biochemical parameters in serum and haematological parameters, and urine analysis were performed to evaluate the safety of 5-Loxin® in OA patients.Results
Seventy patients completed the study. At the end of the study, both doses of 5-Loxin® conferred clinically and statistically significant improvements in pain scores and physical function scores in OA patients. Interestingly, significant improvements in pain score and functional ability were recorded in the treatment group supplemented with 250 mg 5-Loxin® as early as 7 days after the start of treatment. Corroborating the improvements in pain scores in treatment groups, we also noted significant reduction in synovial fluid matrix metalloproteinase-3. In comparison with placebo, the safety parameters were almost unchanged in the treatment groups.Conclusion
5-Loxin® reduces pain and improves physical functioning significantly in OA patients; and it is safe for human consumption. 5-Loxin® may exert its beneficial effects by controlling inflammatory responses through reducing proinflammatory modulators, and it may improve joint health by reducing the enzymatic degradation of cartilage in OA patients.Trail Registration
(Clinical trial registration number: ISRCTN05212803.) 相似文献7.
Campbell JH Burdo TH Autissier P Bombardier JP Westmoreland SV Soulas C González RG Ratai EM Williams KC 《PloS one》2011,6(4):e18688
Background
Minocycline is a tetracycline antibiotic that has been proposed as a potential conjunctive therapy for HIV-1 associated cognitive disorders. Precise mechanism(s) of minocycline''s functions are not well defined.Methods
Fourteen rhesus macaques were SIV infected and neuronal metabolites measured by proton magnetic resonance spectroscopy (1H MRS). Seven received minocycline (4 mg/kg) daily starting at day 28 post-infection (pi). Monocyte expansion and activation were assessed by flow cytometry, cell traffic to lymph nodes, CD16 regulation, viral replication, and cytokine production were studied.Results
Minocycline treatment decreased plasma virus and pro-inflammatory CD14+CD16+ and CD14loCD16+ monocytes, and reduced their expression of CD11b, CD163, CD64, CCR2 and HLA-DR. There was reduced recruitment of monocyte/macrophages and productively infected cells in axillary lymph nodes. There was an inverse correlation between brain NAA/Cr (neuronal injury) and circulating CD14+CD16+ and CD14loCD16+ monocytes. Minocycline treatment in vitro reduced SIV replication CD16 expression on activated CD14+CD16+ monocytes, and IL-6 production by monocytes following LPS stimulation.Conclusion
Neuroprotective effects of minocycline are due in part to reduction of activated monocytes, monocyte traffic. Mechanisms for these effects include CD16 regulation, reduced viral replication, and inhibited immune activation. 相似文献8.
Barney S. Graham Mary E. Enama Martha C. Nason Ingelise J. Gordon Sheila A. Peel Julie E. Ledgerwood Sarah A. Plummer John R. Mascola Robert T. Bailer Mario Roederer Richard A. Koup Gary J. Nabel the VRC Study Team 《PloS one》2013,8(4)
Background
DNA vaccine immunogenicity has been limited by inefficient delivery. Needle-free delivery of DNA using a CO2-powered Biojector® device was compared to delivery by needle and syringe and evaluated for safety and immunogenicity.Methods
Forty adults, 18–50 years, were randomly assigned to intramuscular (IM) vaccinations with DNA vaccine, VRC-HIVDNA016-00-VP, (weeks 0, 4, 8) by Biojector® 2000™ or needle and syringe (N/S) and boosted IM at week 24 with VRC-HIVADV014-00-VP (rAd5) with N/S at 1010 or 1011 particle units (PU). Equal numbers per assigned schedule had low (≤500) or high (>500) reciprocal titers of preexisting Ad5 neutralizing antibody.Results
120 DNA and 39 rAd5 injections were given; 36 subjects completed follow-up research sample collections. IFN-γ ELISpot response rates were 17/19 (89%) for Biojector® and 13/17 (76%) for N/S delivery at Week 28 (4 weeks post rAd5 boost). The magnitude of ELISpot response was about 3-fold higher in Biojector® compared to N/S groups. Similar effects on response rates and magnitude were observed for CD8+, but not CD4+ T-cell responses by ICS. Env-specific antibody responses were about 10-fold higher in Biojector-primed subjects.Conclusions
DNA vaccination by Biojector® was well-tolerated and compared to needle injection, primed for greater IFN-γ ELISpot, CD8+ T-cell, and antibody responses after rAd5 boosting.Trial Registration
ClinicalTrials.gov NCT00109629相似文献9.
Alberto Migliore Umberto Massafra Emanuele Bizzi Francesca Vacca Severino Martin-Martin Mauro Granata Andrea Alimonti Sandro Tormenta 《Arthritis research & therapy》2009,11(6):R183
Introduction
Comparison of intra-articular bacterial-derived hyaluronic acid (Hyalubrix®) (HA) with local analgesia (mepivacaine) for osteoarthritis (OA) of the hip.Methods
A pilot prospective, double-blind, 6-month randomized trial of 42 patients with hip OA. HA or mepivacaine was administered twice (once a month) under ultrasound guidance. Efficacy measurements included the Lequesne''s algofunctional index, a visual analog scale for pain, concomitant use of analgesia, patient and physician global measurement, and safety.Results
Patients in the HA group exhibited a significantly reduced Lequesne''s algofunctional index 3 and 6 months after treatment (P < 0.001) and significantly reduced visual analog scale pain scores 3 and 6 months after treatment (P < 0.05) compared with the local anesthetic group. All primary and secondary measures were significantly improved versus baseline, but other than the above were not different from each other at 3 or 6 months. Adverse effects were minimal.Conclusions
This comparative study suggests a beneficial effect and safety of intra-articular HA in the management of hip OA.Trial registration number
ISRCTN39397064. 相似文献10.
Keiko Aida-Yasuoka Christine Peoples Hidekata Yasuoka Pamela Hershberger Katelynn Thiel Jane A Cauley Thomas A Medsger Jr Carol A Feghali-Bostwick 《Arthritis research & therapy》2013,15(1):R10
Introduction
Systemic sclerosis (SSc) is more prevalent in women. Our goal is to determine the effects of 17β-estradiol (E2) on the development of fibrosis and to compare circulating levels of estrogens in SSc patients and healthy controls.Methods
Using primary human dermal fibroblasts, we evaluated the effect of E2 on fibronectin (FN) expression with and without the estrogen receptor (ER) antagonist ICI 182,780, inhibitors of signaling, propyl-pyrazole-triol, an ERα specific ligand, and genistein, an ERβ selective ligand, to identify the signaling pathways mediating E2''s effect. We confirmed the fibrotic effect of E2 in human skin using an ex vivo organ culture model. Lastly, we measured levels of E2 and estrone in serum samples from SSc patients with diffuse cutaneous involvement and healthy controls using mass spectrometry.Results
E2 increased expression of FN in dermal fibroblasts. ICI 182,780, inositol-1,4,5-triphosphate inhibitor, and p38 mitogen-activated protein kinase inhibitor blocked the effects of E2 on FN. Propyl-pyrazole-triol, but not genistein, significantly increased FN expression. Ex vivo, E2 induced fibrosis of human skin. The effects of E2 were abrogated by ICI 182,780. Circulating levels of E2 and estrone were significantly increased in sera of patients with diffuse cutaneous SSc.Conclusion
Our findings implicate estrogens in the fibrotic process and may explain the preponderance of SSc in women. ICI 182,780 or other ER signaling antagonists may be effective agents for the treatment of fibrosis. 相似文献11.
Wouter Huvenne Ellen A Lanckacker Olga Krysko Ken R Bracke Tine Demoor Peter W Hellings Guy G Brusselle Guy F Joos Claus Bachert Tania Maes 《Respiratory research》2011,12(1):69
Background
Cigarette smoke (CS) is a major risk factor for the development of COPD. CS exposure is associated with an increased risk of bacterial colonization and respiratory tract infection, because of suppressed antibacterial activities of the immune system and delayed clearance of microbial agents from the lungs. Colonization with Staphylococcus aureus results in release of virulent enterotoxins, with superantigen activity which causes T cell activation.Objective
To study the effect of Staphylococcus aureus enterotoxin B (SEB) on CS-induced inflammation, in a mouse model of COPD.Methods
C57/Bl6 mice were exposed to CS or air for 4 weeks (5 cigarettes/exposure, 4x/day, 5 days/week). Endonasal SEB (10 μg/ml) or saline was concomitantly applied starting from week 3, on alternate days. 24 h after the last CS and SEB exposure, mice were sacrificed and bronchoalveolar lavage (BAL) fluid and lung tissue were collected.Results
Combined exposure to CS and SEB resulted in a raised number of lymphocytes and neutrophils in BAL, as well as increased numbers of CD8+ T lymphocytes and granulocytes in lung tissue, compared to sole CS or SEB exposure. Moreover, concomitant CS/SEB exposure induced both IL-13 mRNA expression in lungs and goblet cell hyperplasia in the airway wall. In addition, combined CS/SEB exposure stimulated the formation of dense, organized aggregates of B- and T- lymphocytes in lungs, as well as significant higher CXCL-13 (protein, mRNA) and CCL19 (mRNA) levels in lungs.Conclusions
Combined CS and SEB exposure aggravates CS-induced inflammation in mice, suggesting that Staphylococcus aureus could influence the pathogenesis of COPD. 相似文献12.
Acceleration of Bone Repair in NOD/SCID Mice by Human Monoosteophils,Novel LL-37-Activated Monocytes
Background
An incomplete understanding of bone forming cells during wound healing and ectopic calcification has led to a search for circulating cells that may fulfill this function. Previously, we showed that monoosteophils, a novel lineage of calcifying/bone-forming cells generated by treatment of monocytes with the natural peptide LL-37, are candidates. In this study, we have analyzed their gene expression profile and bone repair function.Methods and Findings
Human monoosteophils can be distinguished from monocytes, macrophages and osteoclasts by their unique up-regulation of integrin α3 and down-regulation of CD14 and CD16. Monoosteophils express high mRNA and protein levels of SPP1 (osteopontin), GPNMB (osteoactivin), CHI3L1 (cartilage glycoprotein-39), CHIT1 (Chitinase 1), MMP-7, CCL22 and MAPK13 (p38MAPKδ). Monocytes from wild type, but not MAPK13 KO mice are also capable of monoosteophil differentiation, suggesting that MAPK13 regulates this process. When human monoosteophils were implanted in a freshly drilled hole in mid-diaphyseal femurs of NOD/SCID mice, significant bone repair required only 14 days compared to at least 24 days in control treated injuries.Conclusion
Human derived monoosteophils, characterized as CD45+α3+α3β+CD34−CD14−BAP (bone alkaline phosphatase)− cells, can function in an animal model of bone injury. 相似文献13.
Lena Uller Cecilia Ahlstr?m Emanuelsson Morgan Andersson Jonas S Erjef?lt Lennart Greiff Carl G Persson 《Respiratory research》2010,11(1):54
Background
It is widely assumed that apoptosis of eosinophils is a central component of resolution of allergic airway disease. However, this has not been demonstrated in human allergic airways in vivo. Based on animal in vivo observations we hypothesised that steroid-induced resolution of human airway eosinophilic inflammation involves inhibition of CCL5 (RANTES), a CC-chemokine regulating eosinophil and lymphocyte traffic, and elimination of eosinophils without evident occurrence of apoptotic eosinophils in the diseased tissue.Objective
To determine mucosal eosinophilia, apoptotic eosinophils, general cell apoptosis and cell proliferation, and expression of CCL5 and CCL11 (eotaxin) in human allergic airway tissues in vivo at resolution of established symptomatic eosinophilic inflammation.Methods
Twenty-one patients with intermittent (birch and/or grass) allergic rhinitis received daily nasal allergen challenges for two seven days'' periods separated by more than two weeks washout. Five days into these "artificial pollen seasons", nasal treatment with budesonide was instituted and continued for six days in a double blinded, randomized, placebo-controlled, and crossover design. This report is a parallel group comparison of nasal biopsy histochemistry data obtained on the final day of the second treatment period.Results
Treatments were instituted when clinical rhinitis symptoms had been established. Compared to placebo, budesonide reduced tissue eosinophilia, and subepithelial more than epithelial eosinophilia. Steroid treatment also attenuated tissue expression of CCL5, but CCL11 was not reduced. General tissue cell apoptosis and epithelial cell proliferation were reduced by budesonide. However, apoptotic eosinophils were not detected in any biopsies, irrespective of treatment.Conclusions
Inhibition of CCL5-dependent recruitment of cells to diseased airway tissue, and reduced cell proliferation, reduced general cell apoptosis, but not increased eosinophil apoptosis, are involved in early phase steroid-induced resolution of human allergic rhinitis. 相似文献14.
Saederup N Cardona AE Croft K Mizutani M Cotleur AC Tsou CL Ransohoff RM Charo IF 《PloS one》2010,5(10):e13693
Background
Monocyte subpopulations distinguished by differential expression of chemokine receptors CCR2 and CX3CR1 are difficult to track in vivo, partly due to lack of CCR2 reagents.Methodology/Principal Findings
We created CCR2-red fluorescent protein (RFP) knock-in mice and crossed them with CX3CR1-GFP mice to investigate monocyte subset trafficking. In mice with experimental autoimmune encephalomyelitis, CCR2 was critical for efficient intrathecal accumulation and localization of Ly6Chi/CCR2hi monocytes. Surprisingly, neutrophils, not Ly6Clo monocytes, largely replaced Ly6Chi cells in the central nervous system of these mice. CCR2-RFP expression allowed the first unequivocal distinction between infiltrating monocytes/macrophages from resident microglia.Conclusion/Significance
These results refine the concept of monocyte subsets, provide mechanistic insight about monocyte entry into the central nervous system, and present a novel model for imaging and quantifying inflammatory myeloid populations. 相似文献15.
Objective
To determine the reliability and validity of the Multimedia Activity Recall for Children and Adults (MARCA) in people with chronic obstructive pulmonary disease (COPD).Design
People with COPD and their carers completed the Multimedia Activity Recall for Children and Adults (MARCA) for four, 24-hour periods (including test-retest of 2 days) while wearing a triaxial accelerometer (Actigraph GT3X+®), a multi-sensor armband (Sensewear Pro3®) and a pedometer (New Lifestyles 1000®).Setting
Self reported activity recalls (MARCA) and objective activity monitoring (Accelerometry) were recorded under free-living conditions.Participants
24 couples were included in the analysis (COPD; age 74.4±7.9 yrs, FEV1 54±13% Carer; age 69.6±10.9 yrs, FEV1 99±24%).Interventions
Not applicable.Main Outcome Measure(s)
Test-retest reliability was compared for MARCA activity domains and different energy expenditure zones. Validity was assessed between MARCA-derived physical activity level (in metabolic equivalent of task (MET) per minute), duration of moderate to vigorous physical activity (min) and related data from the objective measurement devices. Analysis included intra-class correlation coefficients (ICC), Bland-Altman analyses, paired t-tests (p) and Spearman''s rank correlation coefficients (rs).Results
Reliability between occasions of recall for all activity domains was uniformly high, with test-retest correlations consistently >0.9. Validity correlations were moderate to strong (rs = 0.43–0.80) across all comparisons. The MARCA yields comparable PAL estimates and slightly higher moderate to vigorous physical activity (MVPA) estimates.Conclusion
In older adults with chronic illness, the MARCA is a valid and reliable tool for capturing not only the time and energy expenditure associated with physical and sedentary activities but also information on the types of activities. 相似文献16.
Jeannine Günther Angela Kill Mike Oliver Becker Harald Heidecke Judith Rademacher Elise Siegert Mislav Radi? Gerd-Rüdiger Burmester Duska Dragun Gabriela Riemekasten 《Arthritis research & therapy》2014,16(2):R65
Introduction
Agonistic autoantibodies (Aabs) against the angiotensin II receptor type 1 (AT1R) and the endothelin receptor type A (ETAR) have been identified in patients with systemic sclerosis (SSc). In our present study, we examined the expression of the AT1R and the ETAR in human immune cells and the pathological effects mediated through these receptors by their corresponding Aabs.Methods
Protein expression of AT1R and ETAR on peripheral blood mononuclear cells (PBMCs) from healthy individuals and SSc patients was analyzed using flow cytometry, and mRNA expression of both receptors in PBMCs from healthy donors was examined by real-time PCR. In addition, PBMCs from healthy donors were stimulated in vitro with affinity-purified immunoglobulin G (IgG) fractions from SSc patients positive for AT1R and ETAR Aabs, as well as with IgG from healthy donors serving as controls. Alterations in cell surface marker expression, cytokine secretion and chemotactic motility were analyzed using flow cytometry, enzyme-linked immunosorbent assays and chemotaxis assays, respectively. The results were correlated with the characteristics and clinical findings of the IgG donors.Results
Both AT1R and ETAR were expressed on PBMCs in humans. Protein expression of both receptors was decreased in SSc patients compared with that of healthy donors and declined during the course of disease. IgG fractions of SSc patients positive for AT1R and ETAR Aabs induced T-cell migration in an Aab level–dependent manner. Moreover, IgG of SSc patients stimulated PBMCs to produce more interleukin 8 (IL-8) and chemokine (C-C motif) ligand 18 (CCL18) than did the IgG of healthy donors. All effects were significantly reduced by selective AT1R and ETAR antagonists. Statistical analysis revealed an association of SSc-IgG induced high IL-8 concentrations with an early disease stage and of high CCL18 concentrations with lung fibrosis onset and vascular complications in the respective IgG donors.Conclusion
In our present study, we could demonstrate the expression of both AT1R and ETAR on human peripheral T cells, B cells and monocytes. The decreased receptor expression in SSc patients, the inflammatory and profibrotic effects upon Aab stimulation of PBMCs in vitro and the associations with clinical findings suggest a role for Aab-induced activation of immune cells mediated by the AT1R and the ETAR in the pathogenesis or even the onset of the disease. 相似文献17.
18.
Lehmann LE Hauser S Malinka T Klaschik S Weber SU Schewe JC Stüber F Book M 《PloS one》2011,6(2):e17146
Background
Urinary tract infections (UTI) are frequent in outpatients. Fast pathogen identification is mandatory for shortening the time of discomfort and preventing serious complications. Urine culture needs up to 48 hours until pathogen identification. Consequently, the initial antibiotic regimen is empirical.Aim
To evaluate the feasibility of qualitative urine pathogen identification by a commercially available real-time PCR blood pathogen test (SeptiFast®) and to compare the results with dipslide and microbiological culture.Design of study
Pilot study with prospectively collected urine samples.Setting
University hospital.Methods
82 prospectively collected urine samples from 81 patients with suspected UTI were included. Dipslide urine culture was followed by microbiological pathogen identification in dipslide positive samples. In parallel, qualitative DNA based pathogen identification (SeptiFast®) was performed in all samples.Results
61 samples were SeptiFast® positive, whereas 67 samples were dipslide culture positive. The inter-methodological concordance of positive and negative findings in the gram+, gram- and fungi sector was 371/410 (90%), 477/492 (97%) and 238/246 (97%), respectively. Sensitivity and specificity of the SeptiFast® test for the detection of an infection was 0.82 and 0.60, respectively. SeptiFast® pathogen identifications were available at least 43 hours prior to culture results.Conclusion
The SeptiFast® platform identified bacterial DNA in urine specimens considerably faster compared to conventional culture. For UTI diagnosis sensitivity and specificity is limited by its present qualitative setup which does not allow pathogen quantification. Future quantitative assays may hold promise for PCR based UTI pathogen identification as a supplementation of conventional culture methods. 相似文献19.
Vasiliki-Kalliopi K Bournia Konstantina D Diamanti Panayiotis G Vlachoyiannopoulos Haralampos M Moutsopoulos 《Arthritis research & therapy》2010,12(2):R47
Introduction
A subgroup of patients with primary Sjögren''s Syndrome (SS) and positive anticentromere antibodies (ACA) were recognized as having features intermediate between SS and systemic sclerosis (SSc). Our goal was to describe this group clinically and serologically and define its tendency to evolve to full blown SSc.Methods
Among 535 patients with primary SS we identified 20 ACA positive (ACA+/SS). We compared them to 61 randomly selected ACA negative SS patients (ACA-/SS), 31 ACA positive SSc patients with sicca manifestations [SSc/(+) sicca] and 20 ACA positive SSc patients without sicca manifestations [SSc/(-) sicca].Results
Prevalence of ACA among SS patients was 3.7%. Cases and controls did not differ in sex ratio and age at disease onset. ACA+/SS patients had a lower prevalence of dry eyes, hypergammaglobulinaemia, anti-Ro and anti-La antibodies and a higher prevalence of Raynaud''s phenomenon and dysphagia compared to ACA-/SS patients. They also had lower prevalence of telangiectasias, puffy fingers, sclerodactyly, Raynaud''s phenomenon, digital ulcers and gastroesophageal reflux in comparison to both of the SSc subgroups and a lower prevalence of dyspnoea and lung fibrosis compared to the SSc/(+) sicca subgroup. Two patients originally having ACA+/SS evolved to full blown SSc. Four deaths occurred, all among SSc patients. Kaplan Meier analysis showed a significant difference between cases and controls in time from disease onset to development of gastroesophageal reflux, telangiectasias, digital ulcers, arthritis, puffy fingers, xerostomia, hypergammaglobulinaemia and dysphagia.Conclusions
ACA+/SS has a clinical phenotype intermediate between ACA-/SS and SSc and shows little tendency to evolve to SSc. 相似文献20.
Sasan Partovi Anja-Carina Schulte Markus Aschwanden Daniel Staub Daniela Benz Stephan Imfeld Bj?rn Jacobi Pavel Broz Kurt A J?ger Martin Takes Rolf W Huegli Deniz Bilecen Ulrich A Walker 《Arthritis research & therapy》2012,14(5):R209