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81.
82.
Richard Macaulay Natalie E. RiddellStephen J. Griffiths Arne N. AkbarSian M. Henson 《Human immunology》2013
The dysregulated immune response to CMV constitutes a major force driving T cell immunosenescence and growing evidence suggests that it is not a benign virus in old age. We show here that the PD-1/L pathway defines a reversible defect in CMV specific CD8+ T cell proliferative responses in both young and old individuals. More specifically, highly differentiated CD45RA+CD27− CMV-specific CD8+ T cells exhibit a proliferative deficit compared their central and effector memory counterparts, which is reversed following PD-L blockade. However, we also report that HLA-B∗07/TPR specific CD8+ T cells express higher levels of PD-1 than HLA-A∗02/NLV specific cells and HLA-A∗02 individuals show a higher proliferative response to PD-L blockade, than HLA-B∗07 individuals, which we postulate may be due to the differing functional avidities for these two CMV-specific CD8+ T cells populations. Nevertheless data presented here demonstrate that CMV-specific CD8+ T cells can be functionally enhanced by perturbation of the PD-1/L signalling pathway, whose manipulation may provide a therapeutic modality to combat age-associated immune decline. 相似文献
83.
Amaia Cipitria Johannes C. Reichert Devakar R. Epari Siamak Saifzadeh Arne Berner Hanna Schell Manav Mehta Michael A. Schuetz Georg N. Duda Dietmar W. Hutmacher 《Biomaterials》2013
The transplantation of autologous bone graft as a treatment for large bone defects has the limitation of harvesting co-morbidity and limited availability. This drives the orthopaedic research community to develop bone graft substitutes. Routinely, supra-physiological doses of bone morphogenetic proteins (BMPs) are applied perpetuating concerns over undesired side effects and cost of BMPs. We therefore aimed to design a composite scaffold that allows maintenance of protein bioactivity and enhances growth factor retention at the implantation site. Critical-sized defects in sheep tibiae were treated with the autograft and with two dosages of rhBMP-7, 3.5 mg and 1.75 mg, embedded in a slowly degradable medical grade poly(ε-caprolactone) (PCL) scaffold with β-tricalcium phosphate microparticles (mPCL–TCP). Specimens were characterised by biomechanical testing, microcomputed tomography and histology. Bridging was observed within 3 months for the autograft and both rhBMP-7 treatments. No significant difference was observed between the low and high rhBMP-7 dosages or between any of the rhBMP-7 groups and autograft implantation. Scaffolds alone did not induce comparable levels of bone formation compared to the autograft and rhBMP-7 groups. In summary, the mPCL–TCP scaffold with the lower rhBMP-7 dose led to equivalent results to autograft transplantation or the high BMP dosage. Our data suggest a promising clinical future for BMP application in scaffold-based bone tissue engineering, lowering and optimising the amount of required BMP. 相似文献
84.
Evelien Platje Lucres M.C. Jansen Adrian Raine Susan J.T. Branje Theo A.H. Doreleijers Marjan de Vries-Bouw Arne Popma Pol A.C. van Lier Hans M. Koot Wim H.J. Meeus Robert R.J.M. Vermeiren 《Biological psychology》2013
Although several studies have associated antisocial behavior with decreased cortisol awakening responses (CAR), studies in adolescent samples yielded inconsistent results. In adolescence however, the CAR develops and antisocial behavior is heterogeneous in type and persistence. Therefore this longitudinal study compared persistent aggressive and rule-breaking adolescents to low aggressive and rule-breaking adolescents on the development of the CAR from ages 15 to 17 (N = 390). Persistently high aggressive adolescents showed decreased cortisol levels at awakening consistently over the years (Δχ2(1) = 6.655, p = .01) as compared to low aggressive adolescents. No differences between adolescents showing persistent high rule-breaking and low rule-breaking were found. This longitudinal study is the first to show that persistent aggression, but not rule-breaking behavior, is related to neurobiological alterations. Moreover, despite development of the CAR over adolescence, the decrease in cortisol is consistent over time in persistent high aggressive adolescents, which is an important prerequisite for the prediction of persistent aggression. 相似文献
85.
Dekkers Tycho J. Huizenga Hilde M. Bult Jente Popma Arne Boyer Bianca E. 《European child & adolescent psychiatry》2021,30(4):657-669
European Child & Adolescent Psychiatry - Parents of children with ADHD experience several difficulties while raising their children and report lower levels of knowledge about their... 相似文献
86.
Lene Plhaugen Carole H Sudre Sandra Tecelao Arne Nakling Ina S Almdahl Lisa F Kalheim M Jorge Cardoso Stein H Johnsen Arvid Rongve Dag Aarsland Atle Bjrnerud Per Selnes Tormod Fladby 《Journal of cerebral blood flow and metabolism》2021,41(5):1162
White matter hyperintensities (WMHs) are associated with vascular risk and Alzheimer’s disease. In this study, we examined relations between WMH load and distribution, amyloid pathology and vascular risk in 339 controls and cases with either subjective (SCD) or mild cognitive impairment (MCI). Regional deep (DWMH) and periventricular (PWMH) WMH loads were determined using an automated algorithm. We stratified on Aβ1-42 pathology (Aβ+/−) and analyzed group differences, as well as associations with Framingham Risk Score for cardiovascular disease (FRS-CVD) and age. Occipital PWMH (p = 0.001) and occipital DWMH (p = 0.003) loads were increased in SCD-Aβ+ compared with Aβ− controls. In MCI-Aβ+ compared with Aβ− controls, there were differences in global WMH (p = 0.003), as well as occipital DWMH (p = 0.001) and temporal DWMH (p = 0.002) loads. FRS-CVD was associated with frontal PWMHs (p = 0.003) and frontal DWMHs (p = 0.005), after adjusting for age. There were associations between global and all regional WMH loads and age. In summary, posterior WMH loads were increased in SCD-Aβ+ and MCI-Aβ+ cases, whereas frontal WMHs were associated with vascular risk. The differences in WMH topography support the use of regional WMH load as an early-stage marker of etiology. 相似文献
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89.
Hui Wu Daniel Haag Thomas Muley Arne Warth Marc Zapatka Grischa Toedt Armin Pscherer Meinhard Hahn Ralf J. Rieker David L. Wachter Michael Meister Philipp Schnabel Karin Müller‐Decker Michael A. Rogers Hans Hoffmann Peter Lichter 《Genes, chromosomes & cancer》2013,52(3):250-264
Invasion is a critical step in lung tumor progression. The interaction between tumor cells and their surroundings may play an important role in tumor invasion and metastasis. To better understand the mechanisms of tumor invasion and tumor–microenvironment interactions in lung tumors, total RNA was isolated from the inner tumor, tumor invasion front, adjacent lung, and distant normal lung tissue from 17 patients with primary squamous cell lung carcinoma using punch‐aided laser capture microdissection. Messenger RNA expression profiles were obtained by microarray analysis, and microRNA profiles were generated from eight of these samples using TaqMan Low Density Arrays. Statistical analysis of the expression data showed extensive changes in gene expression in the inner tumor and tumor front compared with the normal lung and adjacent lung tissue. Only a few genes were differentially expressed between tumor front and the inner tumor. Several genes were validated by immunohistochemistry. Evaluation of the microRNA data revealed zonal expression differences in nearly a fourth of the microRNAs analyzed. Validation of selected microRNAs by in situ hybridization demonstrated strong expression of hsa‐miR‐196a in the inner tumor; moderate expression of hsa‐miR‐224 in the inner tumor and tumor front, and strong expression of hsa‐miR‐650 in the adjacent lung tissue. Pathway analysis placed the majority of genes differentially expressed between tumor and nontumor cells in intrinsic processes associated with inflammation and extrinsic processes related to lymphocyte physiology. Genes differentially expressed between the inner tumor and the adjacent lung/normal lung tissue affected pathways of arachidonic acid metabolism and eicosanoid signaling. © 2012 Wiley Periodicals, Inc. 相似文献
90.
Meschi Nastaran Vanhoenacker Anke Strijbos Olaf Camargo dos Santos Bernardo Rubbers Eléonore Peeters Valerie Curvers Frederik Van Mierlo Maarten Geukens Arne Fieuws Steffen Verbeken Eric Lambrechts Paul 《Clinical oral investigations》2020,24(12):4439-4453
Clinical Oral Investigations - The aim of this study was to assess in a multi-modular manner the bone healing 1 year post root-end surgery (RES) with leukocyte- and platelet-rich fibrin... 相似文献