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Summary Autopsied brains from 55 patients with dementia between 59–95 years of age (mean age 77.9±8.1 years) and 19 non-demented individuals between 46–91 years of age (mean age 74.3±10.5 years) were examined to establish histopathological criteria for normal ageing, primary degenerative [Alzheimer's disease (AD)/senile dementia of Alzheimer type (SDAT)] and vascular (multi-infarct) dementia (MID) disorders. Senile/neuritic plaques, neurofibrillary tangles, microscopic infarcts and perivascular serum protein deposits were quantified in the frontal lobe (Brodmann area 10) and in the hippocampus. The demented patients were classified according to the DSM-III criteria into AD/SDAT and MID. Operationally defined histopathological criteria for dementias, based on the degree/amount of the histopathological changes seen in aged non-demented patients, were postulated. The demented patients were clearly separable into three histopathological types, namely AD/SDAT, MID and AD-MID, the dementia type where both the degenerative and the vascular changes are coexistent in greater extent than are seen in the non-demented individuals. Using general clinical, gross neuroanatomical and histopathological data three separate dementia classes, namely AD/SDAT, MID and AD-MID, were visualized in two-dimensional space by multivariate data analysis. This analysis revealed that the pathology in the AD-MID patients was not merely a linear combination of the pathology in AD/SDAT and MID, indicating that AD-MID might represent a dementia type of its own. The clinical diagnosis for AD/SDAT and MID was certain in only half of the AD/SDAT and one third of the MID cases when evaluated histopathologically and by multivariate data analysis. AD/SDAT, MID and AD-MID were histopathologically diagnosed in 49%, 24% and 27%, respectively, of all the dementia cases studied. Opposite correlation between the number of tangles, plaques and the patient age in non-demented and AD/SDAT cases were observed, indicating that the pathogenesis of tangles and plaques in the two groups of patients might be different and that AD/SDAT might not be a form of an exaggerated ageing process. 相似文献
995.
Cell migration is a fundamental process that is crucial to a variety of physiological events. While traditional approaches have focused on two-dimensional (2D) systems, recent efforts have shifted to studying migration in three-dimensional (3D) matrices. A major distinction that has emerged is the increased importance of cell–matrix interactions in 3D environments. In particular, cell motility in 3D matrices is more dependent on matrix metalloproteinases (MMPs) to degrade steric obstacles than in 2D systems. In this study, we implement the effects of MMP-mediated proteolysis in a force-based computational model of 3D migration, testing two matrix ligand–MMP relationships that have been observed experimentally: linear and log-linear. The model for both scenarios predicts maximal motility at intermediate matrix ligand and MMP levels, with the linear case providing more physiologically compelling results. Recent experimental results suggesting MMP influence on integrin expression are also integrated into the model. While the biphasic behavior is retained, with MMP-integrin feedback peak cell speed is observed in a low ligand, high MMP regime instead of at intermediate ligand and MMP levels for both ligand–MMP relationships. The simulation provides insight into the expanding role of cell–matrix interactions in cell migration in 3D environments and has implications for cancer research. 相似文献
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997.
Ahmed A. Khattab Muhammad S. El-Mekkawy Amira M. Shehata Nermeen A. Whdan 《The Gazette of the Egyptian Paediatric Association》2018,66(2):43-48
Background
Community-acquired pneumonia (CAP) is an important childhood killer. Excessive production of cytokines, including interleukin-6 (IL-6), might be associated with severe disease course but pediatric data is limited.Aim
To assess value of IL-6 in predicting CAP severity in children.Methods
A prospective study conducted on 73 children hospitalized for CAP and 15 healthy controls. Pneumonia severity was evaluated according to World Health Organization (WHO) classification, Respiratory Index of Severity Score (RISC), Predisposition, Insult, Response, Organ dysfunction modified (PIROm score), and Pediatric Respiratory Severity Score (PRESS). Serum IL-6 was measured within 24?h of admission. The primary outcome was occurrence of any pneumonia complications or death within 30?days.Results
IL-6 was significantly higher among patients compared with controls. Unlike CRP, IL-6 was significantly higher among children with severe pneumonia as determined by WHO, PRESS, and RISC (p?=?0.001 for all). IL-6 was significantly higher among children with PICU admission, mechanical ventilation, shock (p?=?0.001 for all), hypoxia (p?<?0.001), and lobar consolidation (p?=?0.042). IL-6 had positive correlations with PRESS (rs=0.8, P?<?0.001), RISC (rs=0.6, p?<?0.001), and PIROm (rs=0.59, p?<?0.001) while a negative correlation was found with Oxygen saturation [r?=??0.61, p?=?0.001]. IL-6 was not significantly correlated with CRP. Receiver Operating Characteristic curve (ROC) analysis revealed large area under the curve (AUC) of IL-6 for prediction of severe pneumonia as classified by WHO, PRESS, and RISC (AUC?=?0.95, 0.94, and 0.89 respectively).Conclusion
IL-6 appears to be valuable for assessment of CAP severity in children compared with conventional biomarkers. 相似文献998.
Klaus Rätzke Maja Wiegemann Muhammad Qasim Shaikh Stephan Harms Rainer Adelung Werner Egger Peter Sperr 《Acta biomaterialia》2010,6(7):2690-2694
Barnacles attach to a wide variety of surfaces underwater and show substrate-specific adhesion mechanisms. Investigating and understanding these mechanisms is a key for developing new technical adhesives. We expected open volume (porosity) at the sub-nanometre scale to occur in barnacle adhesive. With positron annihilation lifetime spectroscopy (PALS) it is possible to detect porosity at the nanometre scale by determining the lifetime of positrons. This method has not been applied to bioadhesives so far. We showed that PALS is a suitable technique for the investigation of the barnacle base and its adhesive with respect to open volume. The results were interpreted using a standard model adapted from polymers. We thereby estimated pore sizes of 0.5 nm. 相似文献
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Muhammad Omar Chohan Bin LiJulie Blanchard Yunn-Chyn TungAgnes T. Heaney Ausma RabeKhalid Iqbal Inge Grundke-Iqbal 《Neurobiology of aging》2011,32(8):1420-1434
Pharmacological enhancement of hippocampal neurogenesis is a therapeutic approach for improvement of cognition in learning and memory disorders such as Alzheimer's disease. Here we report the development of an 11-mer peptide that we designed based on a biologically active region of the ciliary neurotrophic factor. This peptide, Peptide 6, induced proliferation and increased survival and maturation of neural progenitor cells into neurons in the dentate gyrus of normal adult C57BL6 mice. Furthermore, Peptide 6 increased the MAP2 and synaptophysin immunoreactivity in the dentate gyrus. Thirty-day treatment of the mice with a slow release bolus of the peptide implanted subcutaneously improved reference memory of the mice in Morris water maze. Peptide 6 has a plasma half life of over 6 h, is blood-brain barrier permeable, and acts by competitively inhibiting the leukemia inhibitory factor signaling. The fact that Peptide 6 is both neurogenic and neurotrophic and that this peptide is effective when given peripherally, demonstrates its potential for prevention and treatment of learning and memory disorders. 相似文献