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71.
Nedjai B Hitman GA Yousaf N Chernajovsky Y Stjernberg-Salmela S Pettersson T Ranki A Hawkins PN Arkwright PD McDermott MF Turner MD 《Arthritis and rheumatism》2008,58(1):273-283
OBJECTIVE: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal-dominant autoinflammatory condition caused by mutations in the TNFRSF1A gene. The cellular mechanisms by which mutations in this gene trigger inflammation are currently unclear. Because NF-kappaB is the major intracellular signaling component inducing secretion of proinflammatory cytokines, we sought to determine whether differences in the clinical phenotype of patients with TRAPS may be attributable to variable effects of TNFRSF1A mutations on TNFRI expression, localization, or NF-kappaB activity. METHODS: Peripheral blood mononuclear cells were obtained from patients (following informed consent), and cellular nuclear and cytosolic fractions were generated by subcellular fractionation. Localization of IkappaBalpha and NF-kappaB was determined by Western blotting of the resultant fractions. NF-kappaB subunit activity was determined by enzyme-linked immunosorbent assay analysis and confirmed by electrophoretic mobility shift assay. Subcellular localization of TNFRI was determined by immunofluorescence confocal microscopy or by immunoblotting following affinity isolation of plasma membrane by subcellular fractionation. RESULTS: Cells from patients with the fully penetrant C73R mutation had marked activation of the proinflammatory p65 subunit of NF-kappaB. In contrast, cells from patients with the low-penetrant R92Q mutation displayed high levels of DNA binding by the p50 subunit, an interaction previously linked to repression of inflammation. Interestingly, although cells from patients with the C73R mutation have no TNFRI shedding defect, there was nonetheless an unusually high concentration of functional TNFRI at the plasma membrane. CONCLUSION: High levels of TNFRI at the cell surface in patients with the C73R mutation hypersensitizes cells to stimulation by TNF, leading to increased NF-kappaB p65 subunit activation and an exaggerated proinflammatory response. 相似文献
72.
Beyan H Buckley LR Yousaf N Londei M Leslie RD 《Diabetes/metabolism research and reviews》2003,19(2):89-100
Two arms of the immune system, innate and adaptive immunity, differ in their mode of immune recognition. The innate immune system recognizes a few highly conserved structures on a broad range of microorganisms. On the other hand, recognition of self or autoreactivity is generally confined to the adaptive immune response. Whilst autoimmune features are relatively common, they should be distinguished from autoimmune disease that is infrequent. Type 1 diabetes is an immune-mediated disease due to the destruction of insulin secreting cells mediated by aggressive immune responses, including activation of the adaptive immune system following genetic and environmental interaction. Hypotheses for the cause of the immune dysfunction leading to type 1 diabetes include self-reactive T-cell clones that (1) escape deletion in the thymus, (2) escape from peripheral tolerance or (3) escape from homeostatic control with an alteration in the immune balance leading to autoimmunity. Evidence, outlined in this review, raises the possibility that changes in the innate immune system could lead to autoimmunity, by either priming or promoting aggressive adaptive immune responses. Hostile microorganisms are identified by genetically determined surface receptors on innate effector cells, thereby promoting clearance of these invaders. These innate effectors include a few relatively inflexible cell populations such as monocytes/macrophages, dendritic cells (DC), natural killer (NK) cells, natural killer T (NKT) cells and gammadelta T cells. Recent studies have identified abnormalities in some of these cells both in patients with type 1 diabetes and in those at risk of the disease. However, it remains unclear whether these abnormalities in innate effector cells predispose to autoimmune disease. If they were to do so, then modulation of the innate immune system could be of therapeutic value in preventing immune-mediated diseases such as type 1 diabetes. 相似文献
73.
74.
Is salivary IgA level a potential biomarker for immunosuppression in HIV‐positive children? A systematic review and meta‐analysis
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Fawad Javed Zohaib Akram Munerah Saleh Binshabaib Shatha Subhi ALHarthi Sergio Varela Kellesarian Fahim Vohra 《Reviews in medical virology》2017,27(4)
The aim of this systematic review was to determine whether or not assessment of salivary secretory immunoglobulin A (sIgA) levels could be a potential biomarker for immunosuppression in HIV‐positive children. The Patient, Exposure, Comparative, Outcome question was “Is sIgA level a potential biomarker for immunosuppression in HIV‐positive children?” Electronic and manual literature searches were conducted in indexed databases (MEDLINE, PubMed, EMBASE, ScienceDirect, and SCOPUS databases) up to and including June 2017. The primary outcome was total mean salivary levels of IgA among HIV seropositive and seronegative children (controls). The weighted mean differences (WMD) of outcomes and 95% confidence intervals (CI) for total mean salivary IgA levels were calculated using a random effect model. Six studies were included. Three studies showed significantly lower salivary IgA levels in HIV‐infected children compared with controls. Two studies showed comparable IgA levels in HIV infected and controls. One study showed significantly higher levels of salivary IgA in HIV‐infected children as compared to controls. Considering the total mean salivary IgA levels among HIV seropositive and seronegative children, a high degree of heterogeneity (Q value = 254.09, P < .0001, I2 = 98.82%) was noticed among both groups. The overall WMD was not significant (WMD = ?1.18, 95% CI, ?1.91 to ?0.44, P = .39). Whether salivary IgA level is a potential biomarker for immunosuppression in HIV‐positive children remains debatable because of limited information available in the current literature. Further, high‐quality case‐control studies with larger sample size and more solid methodological aspects are required. 相似文献
75.
Improved quantification and mapping of anomalous pulmonary venous flow with four‐dimensional phase‐contrast MRI and interactive streamline rendering
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76.
77.
Efficacy of statin delivery as an adjunct to scaling and root planing in the treatment of chronic periodontitis: A meta‐analysis
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The action of statins in stimulating bone formation and having other pleiotropic effects, such as anti‐inflammatory and immunomodulatory effects, has justified their use as an adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis (CP). The aim of the present study was to evaluate the efficacy of statin delivery as an adjunct to SRP in the treatment of CP. Electronic searches were conducted using the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Oral Health Group Trials Register, up until July 2017. The primary outcome was probing depth (PD), while the secondary outcomes were changes in clinical attachment level (CAL) and bone defect (BD) fill. Eleven studies were included, and all showed significant PD reduction, CAL gain, and BD fill with adjunctive statin delivery compared to SRP alone. The meta‐analysis showed significant improvement in periodontal parameters for atorvastatin (PD: weighted mean difference [WMD] = ?1.84, ?2.56 to ?1.12, P < .001; CAL: WMD = ?2.31, ?3.58 to ?1.03, P < .001; BD fill: WMD = 2.66, ?3.92 to ?1.39, P < .001), simvastatin (PD: WMD = ?1.91, ?2.27 to ?1.55, P < .001; CAL: WMD = ?1.91, ?2.27 to ?1.55, P = .001; BD: WMD = ?1.52, ?2.20 to ?0.85, P < .001), and rosuvastatin (PD: WMD = ?0.94, ?1.32 to ?0.55, P < .001; CAL: WMD = ?1.00, ?1.41 to ?0.60, P < .001; BD fill: WMD = ?1.30, ?1.80 to ?0.79, P < .001). Adjunctive statin delivery appears to be effective in reducing PD, CAL gain, and BD fill in CP, and therefore, these drugs could be a promising therapeutic option for periodontal regeneration in future. 相似文献
78.
Differences between disease-associated endoplasmic reticulum aminopeptidase 1 (ERAP1) isoforms in cellular expression,interactions with tumour necrosis factor receptor 1 (TNF-R1) and regulation by cytokines
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N Yousaf W Y Low A Onipinla C Mein M Caulfield P B Munroe Y Chernajovsky 《Clinical and experimental immunology》2015,180(2):289-304
Endoplasmic reticulum aminopeptidase 1 (ERAP1) processes peptides for major histocompatibility complex (MHC) class I presentation and promotes cytokine receptor ectodomain shedding. These known functions of ERAP1 may explain its genetic association with several autoimmune inflammatory diseases. In this study, we identified four novel alternatively spliced variants of ERAP1 mRNA, designated as ΔExon-11, ΔExon-13, ΔExon-14 and ΔExon-15. We also observed a rapid and differential modulation of ERAP1 mRNA levels and spliced variants in different cell types pretreated with lipopolysaccharide (LPS). We have studied three full-length allelic forms of ERAP1 (R127-K528, P127-K528, P127-R528) and one spliced variant (ΔExon-11) and assessed their interactions with tumour necrosis factor receptor 1 (TNF-R1) in transfected cells. We observed variation in cellular expression of different ERAP1 isoforms, with R127-K528 being expressed at a much lower level. Furthermore, the cellular expression of full-length P127-K528 and ΔExon-11 spliced variant was enhanced significantly when co-transfected with TNF-R1. Isoforms P127-K528, P127-R528 and ΔExon-11 spliced variant associated with TNF-R1, and this interaction occurred in a region within the first 10 exons of ERAP1. Supernatant-derived vesicles from transfected cells contained the full-length and ectodomain form of soluble TNF-R1, as well as carrying the full-length ERAP1 isoforms. We observed marginal differences between TNF-R1 ectodomain levels when co-expressed with individual ERAP1 isoforms, and treatment of transfected cells with tumour necrosis factor (TNF), interleukin (IL)-1β and IL-10 exerted variable effects on TNF-R1 ectodomain cleavage. Our data suggest that ERAP1 isoforms may exhibit differential biological properties and inflammatory mediators could play critical roles in modulating ERAP1 expression, leading to altered functional activities of this enzyme. 相似文献
79.
Tariq S. Marroush Andrew R. Boshara Bassent Botros Philip Vendittelli Zohaib Ahmed Luay Dawood Howard S. Rosman 《Heart & lung : the journal of critical care》2018,47(2):131-135
Background
The rupture of sinus of Valsalva aneurysm (RSoVA) is a rare disorder that affects the integrity of the cardiovascular system, disrupting its dynamics and resulting in a variety of manifestations. In this report, we discuss two cases of RSoVA that we encountered and review similar cases reported in the literature.Methods
literature review of reported cases of RSoVA in PubMed and Google Scholar.Results
A total of 223 cases were found and the final analysis included 225 cases, of which 69% occurred in males and the mean age was 38.9 years.Dyspnea was the most common presenting symptom and 76% of the cases described continuous murmur on examination. The right sinus was affected in 61% of the cases and the fistula connected to the right chambers of the heart 73% of the time.Conclusion
RSoVA is a rare condition that is difficult to diagnose, it should be considered in the right context, particularly in young patients with symptoms of heart failure and the presence of continuous murmur on cardiac examination. 相似文献80.
The depletion of fossil fuels and associated environmental problems have drawn our attention to renewable energy resources in order to meet the global energy demand. Electrocatalytic hydrogen evolution has been considered a potential energy solution due of its high energy density and environment friendly technology. Herein, we have successfully synthesized a noble-metal-free Co–Ni/MoS2 nanocomposite for enhanced electrocatalytic hydrogen evolution. The nanocomposite has been well characterized using HRTEM, elemental mapping, XRD, and XPS analysis. The as-synthesized nanocomposite exhibits a much smaller onset potential and better current density than those of Co–MoS2, Ni–MoS2 and MoS2, with a Tafel value of 49 mV dec−1, which is comparable to that of a commercial Pt/C catalyst. The synergistic effect and interfacial interaction of Co–Ni bimetallic nanoparticles enhances the intrinsic modulation in the electronic structure resulting in an improved HER performance. Moreover, the electrochemical impedance spectroscopic results suggest smaller resistance values for the Co–Ni/MoS2 nanocomposite, compared to those for the charge transfer of bare nanosheets, which increase the faradaic process and in turn enhance the HER kinetics for a better performance. Our as-synthesized Co–Ni/MoS2 nanocomposite holds great potential for the future synthesis of noble-metal-free catalysts.A noble-metal-free Co–Ni/MoS2 nanocomposite was synthesized, which showed enhanced electrocatalytic hydrogen evolution performance. 相似文献