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151.
Marion Munch MD Laurent Meyer MD Thierry Hannedouche MD Kristian Kunz MD Farideh Alenabi MD Patrice Winiszewski MD Philippe Baltzinger MD Agnès Smagala MD Alexandre Klein MD François Dorey MD Dominique Fleury MD Odile Verier-Mine MD Bruno Guerci MD Joëlle Cridlig MD Sophie Borot MD Didier Ducloux MD Nicolas Meyer MD Samy Hadjadj MD François Chantrel MD Laurence Kessler MD 《Diabetes, obesity & metabolism》2020,22(6):978-987
152.
Cornelia Schuh Isabella Wimmer Simon Hametner Lukas Haider Anne-Marie Van Dam Roland S. Liblau Ken J. Smith Lesley Probert Christoph J. Binder Jan Bauer Monika Bradl Don Mahad Hans Lassmann 《Acta neuropathologica》2014,128(2):247-266
Recent data suggest that oxidative injury may play an important role in demyelination and neurodegeneration in multiple sclerosis (MS). We compared the extent of oxidative injury in MS lesions with that in experimental models driven by different inflammatory mechanisms. It was only in a model of coronavirus-induced demyelinating encephalomyelitis that we detected an accumulation of oxidised phospholipids, which was comparable in extent to that in MS. In both, MS and coronavirus-induced encephalomyelitis, this was associated with massive microglial and macrophage activation, accompanied by the expression of the NADPH oxidase subunit p22phox but only sparse expression of inducible nitric oxide synthase (iNOS). Acute and chronic CD4+ T cell-mediated experimental autoimmune encephalomyelitis lesions showed transient expression of p22phox and iNOS associated with inflammation. Macrophages in chronic lesions of antibody-mediated demyelinating encephalomyelitis showed lysosomal activity but very little p22phox or iNOS expressions. Active inflammatory demyelinating lesions induced by CD8+ T cells or by innate immunity showed macrophage and microglial activation together with the expression of p22phox, but low or absent iNOS reactivity. We corroborated the differences between acute CD4+ T cell-mediated experimental autoimmune encephalomyelitis and acute MS lesions via gene expression studies. Furthermore, age-dependent iron accumulation and lesion-associated iron liberation, as occurring in the human brain, were only minor in rodent brains. Our study shows that oxidative injury and its triggering mechanisms diverge in different models of rodent central nervous system inflammation. The amplification of oxidative injury, which has been suggested in MS, is only reflected to a limited degree in the studied rodent models. 相似文献
153.
Adriano Schimmenti Alessia Passanisi Alessia Maria Gervasi Sergio Manzella Francesca Isabella Famà 《Child psychiatry and human development》2014,45(5):588-595
Studies on the role played by attachment attitudes among late adolescents who show Problematic Internet Use (PIU) are still lacking. Three self-report measures concerning attachment attitudes, childhood experiences of abuse, and Internet addiction were administered to 310 students (49 % males) aged 18–19 attending the last year of high school. Students who screened positive for PIU were more likely to be male and to have suffered childhood experiences of physical and sexual abuse; they also scored higher than the other participants on scales assessing anxious and avoidant attachment attitudes. A logistic regression showed that the classification of participants in the PIU group was predicted by male gender, having suffered from physical and sexual abuse in childhood, and preoccupation with relationships. Keeping constant the effects of gender and childhood experiences of abuse in the equation model, increasing values of preoccupation with relationships were reflected by an exponential growth in the probability curve for PIU classification. Findings of the study support the hypothesis that insecure attachment attitudes (particularly the preoccupation with relationships) are involved in the development of PIU among late adolescents. 相似文献
154.
Zorzi M Barbiero C Facoetti A Lonciari I Carrozzi M Montico M Bravar L George F Pech-Georgel C Ziegler JC 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(28):11455-11459
Although the causes of dyslexia are still debated, all researchers agree that the main challenge is to find ways that allow a child with dyslexia to read more words in less time, because reading more is undisputedly the most efficient intervention for dyslexia. Sophisticated training programs exist, but they typically target the component skills of reading, such as phonological awareness. After the component skills have improved, the main challenge remains (that is, reading deficits must be treated by reading more--a vicious circle for a dyslexic child). Here, we show that a simple manipulation of letter spacing substantially improved text reading performance on the fly (without any training) in a large, unselected sample of Italian and French dyslexic children. Extra-large letter spacing helps reading, because dyslexics are abnormally affected by crowding, a perceptual phenomenon with detrimental effects on letter recognition that is modulated by the spacing between letters. Extra-large letter spacing may help to break the vicious circle by rendering the reading material more easily accessible. 相似文献
155.
Knight MJ Pell AJ Bertini I Felli IC Gonnelli L Pierattelli R Herrmann T Emsley L Pintacuda G 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(28):11095-11100
We introduce a new approach to improve structural and dynamical determination of large metalloproteins using solid-state nuclear magnetic resonance (NMR) with (1)H detection under ultrafast magic angle spinning (MAS). The approach is based on the rapid and sensitive acquisition of an extensive set of (15)N and (13)C nuclear relaxation rates. The system on which we demonstrate these methods is the enzyme Cu, Zn superoxide dismutase (SOD), which coordinates a Cu ion available either in Cu(+) (diamagnetic) or Cu(2+) (paramagnetic) form. Paramagnetic relaxation enhancements are obtained from the difference in rates measured in the two forms and are employed as structural constraints for the determination of the protein structure. When added to (1)H-(1)H distance restraints, they are shown to yield a twofold improvement of the precision of the structure. Site-specific order parameters and timescales of motion are obtained by a gaussian axial fluctuation (GAF) analysis of the relaxation rates of the diamagnetic molecule, and interpreted in relation to backbone structure and metal binding. Timescales for motion are found to be in the range of the overall correlation time in solution, where internal motions characterized here would not be observable. 相似文献
156.
Kardys I Oemrawsingh RM Kay IP Jones GT McCormick SP Daemen J Van Geuns RJ Boersma E Van Domburg RT Serruys PW 《Clinical cardiology》2012,35(8):482-489
Background:
This prospective study investigated the association between preprocedural biomarker levels and incident major adverse cardiac events (MACE) in complex patients undergoing percutaneous coronary intervention (PCI) with sirolimus‐eluting stenting.Hypothesis:
Lipoprotein(a) (Lp[a]), interleukin‐10 (IL‐10), and high‐sensitivity C‐reactive protein (CRP) have long‐term prognostic value in patients undergoing PCI.Methods:
Between April 2002 and February 2003, 161 patients were included in the study. Blood was drawn before the procedure, and biomarkers were measured. Patients were followed‐up for MACE (death, nonfatal myocardial infarction, and repeat revascularization). Cox proportional hazard models were used to determine risk of MACE for tertiles of biomarkers. Both 1‐year and long‐term follow‐up (median, 6 years; maximum, 8 years) were evaluated.Results:
Mean age was 59 years, and 68% were men. During long‐term follow‐up, 72 MACE occurred (overall crude cumulative incidence: 45% [95% confidence interval (CI): 37%‐52%]). Lp(a) was associated with a higher 1‐year risk of MACE, with an adjusted hazard ratio (HR) of 3.1 (95% CI: 1.1‐8.6) for the highest vs the lowest tertile. This association weakened and lost significance with long‐term follow‐up. IL‐10 showed a tendency toward an association with MACE. The 1‐year HR was 2.1 (95% CI: 0.92‐5.0). Long‐term follow‐up rendered a similar result. The association of CRP with MACE did not reach statistical significance at 1‐year follow‐up. However, CRP was associated with long‐term risk of MACE, with an HR of 1.9 (95% CI: 1.0‐3.5).Conclusions:
In this prospective study, preprocedural Lp(a) level was associated with short‐term prognosis after PCI. The preprocedural CRP level was associated with long‐term prognosis after PCI. Clin. Cardiol. 2012 DOI: 10.1002/clc.21988 The authors have no funding, financial relationships, or conflicts of interest to disclose. 相似文献157.
Xie YP Chen B Sanders P Guo A Li Y Zimmerman K Wang LC Weiss RM Grumbach IM Anderson ME Song LS 《Hypertension》2012,59(2):355-362
Right ventricular (RV) failure (RVF) is the main cause of death in patients with pulmonary artery hypertension (PAH). Sildenafil, a phosphodiesterase type 5 inhibitor, was approved recently for treatment of PAH patients. However, the mechanisms underlying RV contractile malfunction and the benefits of sildenafil on RV function are not well understood. We aimed to investigate the following: (1) the ultrastructural and excitation-contraction coupling alterations underlying PAH-induced RVF; (2) whether the ultrastructural changes are reversible; and (3) the mechanisms underlying the therapeutic benefits of sildenafil in PAH-RVF. We used a single injection of monocrotaline in Wistar rats to induce pulmonary vascular proliferation, which led to PAH and RVF. RV myocytes displayed severe transverse (T)-tubule loss and disorganization, as well as blunted and dys-synchronous sarcoplasmic reticulum Ca(2+) release. Sildenafil prevented and reversed the monocrotaline-induced PAH and LV filling impairment. Early intervention with sildenafil prevented RV hypertrophy and the development of RVF, T-tubule remodeling, and Ca(2+) handling dysfunction. Although late treatment with sildenafil did not reverse RV hypertrophy in animals with established RVF, RV systolic function was improved. Furthermore, late intervention partially reversed both the impairment of myocyte T-tubule integrity and Ca(2+) handling protein and sarcoplasmic reticulum Ca(2+) release function in monocrotaline-treated rats. In conclusion, PAH-induced increase in RV afterload causes severe T-tubule remodeling and Ca(2+) handling dysfunction in RV myocytes, leading to RV contractile failure. Sildenafil prevents and partially reverses ultrastructural, molecular, and functional remodeling of failing RV myocytes. Reversal of pathological T-tubule remodeling, although incomplete, is achievable without the regression of RV hypertrophy. 相似文献
158.
Fröhlich GM Schoch B Schmid F Keller P Sudano I Lüscher TF Noll G Ruschitzka F Enseleit F 《International journal of cardiology》2012,154(3):328-332
Background
Takotsubo cardiomyopathy (TC) usually is not recognized until heart catheterization reveals typical wall motion abnormalities in the absence of significant coronary artery disease. It was our aim to identify TC by its unique cardiac biomarker profile at an early stage and, preferably, with non-invasive procedures only.Methods
Ratios of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and myoglobin, NT-proBNP and troponin T (TnT), NT-proBNP and creatinekinase-MB (CK-MB) were compared in patients with TC (n = 39), patients with ST-elevation myocardial infarction (STEMI, n = 48) and patients with non-ST-elevation myocardial infarction (NSTEMI, n = 34). Biomarkers were recorded serially at admission and at the three consecutive days. Optimal cut-off values to distinguish TC from STEMI and NSTEMI were calculated with receiver operator characteristic (ROC) curves.Results
At admission a NT-proBNP (ng/l)/myoglobin (μg/l) ratio of 3.8, distinguished TC from STEMI (sensitivity: 89%, specificity: 90%), while a NT-proBNP (ng/l)/myoglobin (μg/l) ratio of 14 separated well between TC and NSTEMI (sensitivity: 65%, specificity: 90%). Best differentiation of TC and ACS was possible with the ratio of peak levels of NT-proBNP (ng/l)/TnT (μg/l). A cut-off value of NT-proBNP (ng/l)/TnT (μg/l) ratio of 2889, distinguished TC from STEMI (sensitivity: 91%, specificity: 95%), while a NT-proBNP (ng/l)/TnT (μg/l) ratio of 5000 separated well between TC and NSTEMI (sensitivity: 83%, specificity: 95%).Conclusions
TC goes along with a singular cardiac biomarker profile, which might be useful to identify patients with TC among patients presenting with acute coronary syndromes (ACS). 相似文献159.
Asthma is a phenotypically heterogeneous disorder of multifactorial origins that affects 300 million people suffering from asthma and more than 250,000 asthma-related deaths each year. Although treatment for asthma has improved, its prevalence continues to increase, particularly in low and middle income countries, or in some ethnic groups in which prevalence was previously low. Observed spatio-temporal variations in the increased prevalence of asthma depend on exposure to environmental factors. Recently, several arguments are also in favor of the involvement of host susceptibility and stress in the observed increase of asthma prevalence. Further?investigations are warranted to better understand mechanisms underlying asthma increase or stagnation. 相似文献
160.
Alessandra Balduini Christian Andrea Di Buduo Alessandro Malara Anna Lecchi Paola Rebuzzini Manuela Currao Isabella Pallotta Joseph A. Jakubowski Marco Cattaneo 《Haematologica》2012,97(11):1657-1665