Potential effects of zinc on information processing in boys with attention deficit hyperactivity disorder

PURPOSE: The aims of the present study were to investigate the relationship between plasma zinc levels and amplitudes and latencies of P1, N2, and P3 in parietal and frontal areas in children with ADHD, and to compare these zinc levels and event-related potentials (ERPs) indices with controls. METHODS: 28 boys with ADHD were divided into two groups according to plasma zinc levels: low zinc group (N=13, zinc level <80 microg/dL) and zinc non-deficient group (N=15, zinc level >or=80 microg/dL). ERP indices from parietal and frontal brain regions were recorded in children with ADHD and in 24 normal boys by using an auditory oddball paradigm. Plasma zinc levels were measured by an atomic absorption spectrophotometer. RESULTS: The plasma zinc levels were significantly lower in both ADHD groups (means are 65.8 microg/dL in low zinc group and 89.5 microg/dL in zinc non-deficient group) than controls (mean: 107.8 microg/dL; both p values <0.017). In ADHD compared to controls, the amplitudes of P3 in frontal and parietal regions were significantly lower, and the latency of P3 in parietal region was significantly longer (all p values <0.017). In low zinc ADHD group compared to zinc non-deficient ADHD group, the latencies of N2 in frontal and parietal region were significantly shorter (all p values <0.017). In addition, there was a medium but significant positive correlation between plasma zinc levels and amplitude and latency of frontal N2 wave in ADHD. CONCLUSIONS: These results can suggest that plasma zinc levels might have an effect on information processing in ADHD children, and lower zinc levels seem to affect N2 wave. Since N2 wave changes may reflect a different inhibition process, further studies are warranted to investigate the effect of zinc on inhibitory process in children with ADHD, and in low zinc and non-deficient ADHD groups.     

单克隆抗体免疫交叉反应现象及其原因探讨

本文应用免疫双扩散及免疫印染技术证实了组蛋白与抗人FN和抗人CRP单抗之间发生的免疫交叉反应。借助于电子计算机帮助,分析了交叉反应的分子基础,发现组蛋白和FN之间具有5个氨基酸序列同源区域,同源区域与Pollard 1990年所预测的组蛋白抗原决定簇相一致。文章同时讨论了单抗与不相关抗原发生交叉反应的原因,包括分子模拟。构型表位,电荷空间分布及中间介质诱导等因素。     

原发性孔源性视网膜脱离视网膜下液纤维连接蛋白含量与PVR形成关系的探讨

用ＥＬＩＳＡ方法观察到４１例原发性孔源性网膜脱离患者视网膜下液纤维连接蛋白的含量为０．５～８０ｕｇ／ｍｌ，非ＰＶＲ组２０例，轻度ＰＶＲ组１１例，重度ＰＶＲ组１０例，三组之间有明显差异（Ｐ〈０．００１）。视网膜下液中纤维连接蛋白含量随ＰＶＲ分级增高而增加，而患者血浆中纤维连接蛋白的含量正常，视网膜下液中纤维连接蛋白的含量与血浆中纤维连接蛋白的含量无相关性，视网膜下液中纤维连接蛋白的含量取决于血一视网     

Tissue-associated self-antigens containing exosomes: Role in allograft rejection

Exosomes are extracellular vesicles that express self-antigens (SAgs) and donor human leukocyte antigens. Tissue-specific exosomes can be detected in the circulation following lung, heart, kidney and islet cell transplantations. We collected serum samples from patients who had undergone lung (n?=?30), heart (n?=?8), or kidney (n?=?15) transplantations to isolate circulating exosomes. Exosome purity was analyzed by Western blot, using CD9 exosome-specific markers. Tissue-associated lung SAgs, collagen V (Col-V) and K-alpha 1 tubulin (Kα1T), heart SAgs, myosin and vimentin, and kidney SAgs, fibronectin and collagen IV (Col-IV), were identified using western blot. Lung transplant recipients diagnosed with bronchiolitis obliterans syndrome had exosomes with higher expression of Col-V (4.2-fold) and Kα1T (37.1-fold) than stable. Exosomes isolated from heart transplant recipients diagnosed with coronary artery vasculopathy had a 3.9-fold increase in myosin and a 4.7-fold increase in vimentin compared with stable. Further, Kidney transplant recipients diagnosed with transplant glomerulopathy had circulating exosomes with a 2-fold increased expression of fibronectin and 2.5-fold increase in Col-IV compared with stable. We conclude that circulating exosomes with tissue associated SAgs have the potential to be a noninvasive biomarker for allograft rejection.     

Nintedanib inhibits epithelial-mesenchymal transition in A549 alveolar epithelial cells through regulation of the TGF-β/Smad pathway

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disorder. Recent studies have suggested that epithelial-mesenchymal transition (EMT) of alveolar epithelial cells influences development of pulmonary fibrosis, which is mediated by transforming growth factor β (TGF-β). Tumor necrosis factor α (TNF-α), an important proinflammatory cytokine in IPF, has been shown to enhance TGF-β-induced EMT. Nintedanib, a multiple tyrosine kinase inhibitor that is currently used to treat IPF, has been shown to suppress EMT in various cancer cell lines. However, the mechanism of EMT inhibition by nintedanib and its effect on TGF-β and TNF-α signaling pathways in alveolar epithelial cells have not been fully elucidated.MethodsA549 alveolar epithelial cells were stimulated with TGF-β2 and TNF-α, and the effects of nintedanib on global gene expression were evaluated using microarray analysis. Furthermore, Smad2/3 phosphorylation was assessed using western blotting.ResultsWe found that in A549 cells, TGF-β2 and TNF-α treatment induces EMT, which was inhibited by nintedanib. Gene ontology analysis showed that nintedanib significantly attenuates the gene expression of EMT-related cellular pathways and the TGF-β signaling pathway, but not in the TNF-α-mediated signaling pathway. Furthermore, hierarchical cluster analysis revealed that EMT-related genes were attenuated in nintedanib-treated cells. Additionally, nintedanib was found to markedly suppress phosphorylation of Smad2/3.ConclusionNintedanib inhibits EMT by mediating EMT-related gene expression and the TGF-β/Smad pathway in A549 alveolar epithelial cells.     

Time‐frequency theta and delta measures index separable components of feedback processing in a gambling task

Previous work using gambling tasks indicate that the feedback negativity (FN) reflects primary or salient stimulus attributes (often gain vs. loss), whereas the feedback‐P300 appears sensitive to secondary stimulus information. A recent time‐frequency approach has characterized separable theta (3–7 Hz) and delta (0–3 Hz) feedback processes, independently sensitive to primary feedback attributes, specifically loss and gain outcomes, respectively. The current study extends this time‐frequency work to evaluate both primary and secondary (relative outcome and outcome magnitude) feedback attributes. Consistent with previous reports, theta indexed an initial, lower‐level response sensitive to the primary (most salient) feedback attributes (specifically losses), while delta was sensitive to both primary attributes (specifically gains) and assessed secondary stimulus features.     

FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies

Brain metastasis is a devastating problem in patients with breast, lung and melanoma tumors. GRP94 and FN14 are predictive biomarkers over-expressed in primary breast carcinomas that metastasized in brain. To further validate these brain metastasis biomarkers, we performed a multicenter study including 318 patients with breast carcinomas. Among these patients, there were 138 patients with metastasis, of whom 84 had brain metastasis. The likelihood of developing brain metastasis increased by 5.24-fold (95%CI 2.83–9.71) and 2.55- (95%CI 1.52–4.3) in the presence of FN14 and GRP94, respectively. Moreover, FN14 was more sensitive than ErbB2 (38.27 vs. 24.68) with similar specificity (89.43 vs. 89.55) to predict brain metastasis and had identical prognostic value than triple negative patients (p < 0.0001). Furthermore, we used GRP94 and FN14 pathways and GUILD, a network-based disease-gene prioritization program, to pinpoint the genes likely to be therapeutic targets, which resulted in FN14 as the main modulator and thalidomide as the best scored drug. The treatment of mice with brain metastasis improves survival decreasing reactive astrocytes and angiogenesis, and down-regulate FN14 and its ligand TWEAK. In conclusion our results indicate that FN14 and GRP94 are prediction/prognosis markers which open up new possibilities for preventing/treating brain metastasis.     

Diagnostic utility of automated indirect immunofluorescence compared to manual indirect immunofluorescence for anti-nuclear antibodies in patients with systemic rheumatic diseases: A systematic review and meta-analysis

Objective

This study aimed to review and compare the analytical and clinical performance of automated indirect immunofluorescence (AIIF) and manual indirect immunofluorescence (MIIF) as anti-nuclear antibody screening assays for patients with systemic rheumatic diseases (SRDs), such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc).