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排序方式: 共有485条查询结果,搜索用时 15 毫秒
1.
Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS 总被引:18,自引:0,他引:18
Storkebaum E Lambrechts D Dewerchin M Moreno-Murciano MP Appelmans S Oh H Van Damme P Rutten B Man WY De Mol M Wyns S Manka D Vermeulen K Van Den Bosch L Mertens N Schmitz C Robberecht W Conway EM Collen D Moons L Carmeliet P 《Nature neuroscience》2005,8(1):85-92
Neurotrophin treatment has so far failed to prolong the survival of individuals affected with amyotrophic lateral sclerosis (ALS), an incurable motoneuron degenerative disorder. Here we show that intracerebroventricular (i.c.v.) delivery of recombinant vascular endothelial growth factor (Vegf) in a SOD1(G93A) rat model of ALS delays onset of paralysis by 17 d, improves motor performance and prolongs survival by 22 d, representing the largest effects in animal models of ALS achieved by protein delivery. By protecting cervical motoneurons, i.c.v. delivery of Vegf is particularly effective in rats with the most severe form of ALS with forelimb onset. Vegf has direct neuroprotective effects on motoneurons in vivo, because neuronal expression of a transgene expressing the Vegf receptor prolongs the survival of SOD1(G93A) mice. On i.c.v. delivery, Vegf is anterogradely transported and preserves neuromuscular junctions in SOD1(G93A) rats. Our findings in preclinical rodent models of ALS may have implications for treatment of neurodegenerative disease in general. 相似文献
2.
Rademakers R Melquist S Cruts M Theuns J Del-Favero J Poorkaj P Baker M Sleegers K Crook R De Pooter T Bel Kacem S Adamson J Van den Bossche D Van den Broeck M Gass J Corsmit E De Rijk P Thomas N Engelborghs S Heckman M Litvan I Crook J De Deyn PP Dickson D Schellenberg GD Van Broeckhoven C Hutton ML 《Human molecular genetics》2005,14(21):3281-3292
3.
Sleegers J 《Psychiatric services (Washington, D.C.)》2000,51(1):100-104
Differences and similarities in homelessness in Amsterdam and New York City were examined, particularly in regard to persons most at risk for homelessness--those with mental illness and with substance abuse problems. The Netherlands is a welfare state where rents are controlled by the national government and more than half of the housing is public housing. Virtually all homeless people in Amsterdam are unemployed and receive some sort of social security benefit. Direct comparisons of the results of American and Dutch studies on homelessness are impossible, mainly because the estimates are uncertain. Because of the Dutch welfare system, Amsterdam has a smaller proportion of homeless people than New York City, although more people are homeless in Amsterdam today than 15 years ago. Neither a lack of affordable housing or sufficient income nor unemployment has been a direct cause of the increase of homelessness. As in New York City, many of the homeless in Amsterdam are mentally ill or have substance use disorders. The increase in the number of homeless people in Amsterdam consists largely of mentally ill people who would have been admitted to a mental hospital 20 years ago and of older, long-term heroin abusers who can no longer live independently. Thus institutional factors such as fragmentation of services and lack of community programs for difficult-to-serve people are a likely explanation of the growing number of homeless people in Amsterdam. 相似文献
4.
Health-related quality of life parameters as prognostic factors in a nonmetastatic breast cancer population: an international multicenter study. 总被引:4,自引:0,他引:4
Fabio Efficace Patrick Therasse Martine J Piccart Corneel Coens Kristel van Steen Marzena Welnicka-Jaskiewicz Tanja Cufer Jaroslaw Dyczka Michail Lichinitser Lois Shepherd Hanneke de Haes Mirjam A Sprangers Andrew Bottomley 《Journal of clinical oncology》2004,22(16):3381-3388
PURPOSE: The purpose of this research was to evaluate whether baseline health-related quality of life (HRQOL) parameters are prognostic factors for survival in locally advanced breast cancer patients. Although the literature highlights the important role of HRQOL parameters in predicting survival in advanced metastatic disease, little evidence exists for earlier stages. PATIENTS AND METHODS: The overall sample consisted of 448 patients randomly assigned to receive cyclophosphamide, epirubicin, and fluorouracil versus epirubicin, cyclophosphamide, and granulocyte colony-stimulating factor. Patients were enrolled in 12 countries. HRQOL baseline scores were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap resampling technique was used to assess the stability of the outcomes. Bootstrap results were then applied for model averaging purposes as a means to account for the observed model selection uncertainty. RESULTS: The final multivariate model retained inflammatory breast cancer (T4d) as the only factor predicting overall survival (OS) with a hazard ratio of 1.375 (95% CI, 1.027 to 1.840; P =.03). The presence of inflammatory breast cancer lowers the median survival time from 6.6 to 4.2 years (36% reduction). None of the preselected HRQOL variables were prognostic for OS or disease-free survival, in either the univariate or multivariate analysis. CONCLUSION: Our findings suggest that baseline HRQOL parameters have no prognostic value in a nonmetastatic breast cancer population. 相似文献
5.
Weidong He Luc Van Puyvelde Norbert De Kimpe Luc Verbruggen Kristel Anthonissen Mark Van der Flaas Jan Bosselaers Simon G Mathenge Francis P Mudida 《Phytotherapy research : PTR》2002,16(1):66-70
Bioassay-guided fractionation of the dichloromethane extracts of the roots and the bark of Zanthoxylum usambarense led to the isolation of two physiologically active compounds, i.e. canthin-6-one 1 (fungicide) and pellitorine 4 (insecticide). Together with oxychelerythrine 2, norchelerythrine 3, (+)-sesamin 5 and (+)-piperitol-3,3-dimethylallyl ether 6, they were isolated for the first time from this plant. 相似文献
6.
Houthoofd K Braeckman BP Lenaerts I Brys K De Vreese A Van Eygen S Vanfleteren JR 《Experimental gerontology》2002,37(12):1359-1369
Dietary restriction (DR) is the most consistent means of extending life span throughout the animal kingdom. Multiple mechanisms by which DR may act have been proposed but none are clearly predominant. We asked whether metabolic rate and stress resistance is altered in Caenorhabditis elegans in response to DR. DR was imposed in two complementary ways: by growing wild-type worms in liquid medium supplemented with reduced concentrations of bacteria and by using eat-2 mutants, which have a feeding defect. Metabolic rate was not reduced when we fed wild-type worms reduced food and was up-regulated in the eat-2 mutants in liquid culture, as assessed by oxygen consumption rate and heat production. The specific activity levels of the antioxidant enzymes superoxide dismutase (SOD) and catalase showed small increases when we reduced food in wild-type worms, but restricted worms acquired no elevated protection against paraquat and hydrogen peroxide. eat-2 mutants showed elevated specific activities of SOD and catalase relative to wild type in liquid culture. These results indicate that the effects imparted by DR and the eat-2 mutation are not identical, and they contradict, at least in C. elegans, the widespread belief that CR acts by lowering the rate of metabolism. 相似文献
7.
Cynthia Tsien Huey Tan Sowmya Sharma Naaventhan Palaniyappan Pramudi Wijayasiri Kristel Leung Jatinder Hayre Elizabeth Mowlem Rachel Kang Peter J Eddowes Emilie Wilkes Suresh V Venkatachalapathy Indra N Guha Lilia Antonova Angela C Cheung William JH Griffiths Andrew J Butler Stephen D Ryder Martin W James Guruprasad P Aithal Aloysious D Aravinthan 《Clinical medicine (London, England)》2021,21(1):e32
8.
Individual quality of life in adults with congenital heart disease: a paradigm shift. 总被引:3,自引:0,他引:3
Philip Moons Kristien Van Deyk Kristel Marquet Els Raes Leentje De Bleser Werner Budts Sabina De Geest 《European heart journal》2005,26(3):298-307
AIMS: During the last decade, a paradigm shift has emerged in the measurement of quality of life, from the use of standard questionnaires towards a more individualized approach. Therefore, this study examined individual quality of life in adults with congenital heart disease and explored potential differences with those reported by matched, healthy control subjects. METHODS AND RESULTS: We examined 579 adults with congenital heart disease. A subsample of 514 of these patients was matched for age, gender, educational level, and employment status with 446 healthy counterparts. Individual quality of life was assessed using the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW). Twelve domains affecting patients' quality of life were identified. Family, job/education, friends, health, and leisure time were the most prominent quality of life domains. Significantly fewer patients than control subjects considered financial means and material well-being and future to be important determinants of quality of life. CONCLUSION: Assessment of quality of life in adults with congenital heart disease that focusses on the individual is appropriate for obtaining in-depth information on issues relevant for patients' quality of life. This represents a paradigm shift in the measurement of this concept. 相似文献
9.
Lize Bollen Marijke Peetermans Miet Peeters Kristel Van Steen Marc F. Hoylaerts Paul J. Declerck Peter Verhamme Ann Gils 《Thrombosis research》2014
Background
Both activated Thrombin Activatable Fibrinolysis Inhibitor (TAFI) and active Plasminogen Activator Inhibitor-1 (PAI-1) attenuate fibrinolysis and may therefore contribute to the pathophysiology of Venous ThromboEmbolism (VTE). Whether increased TAFI and/or PAI-1 concentrations are associated with VTE is unclear.Objective
To study an association of impaired fibrinolysis and VTE using a comprehensive panel of in-house developed assays measuring intact TAFI, activation peptide of TAFI (AP-TAFI), PAI-1 antigen, endogenous PAI-1:t-PA complex (PAI-1:t-PA) and active PAI-1 levels in 102 VTE patients and in 113 healthy controls (HC).Results
Active PAI-1 was significantly higher in VTE patients compared to HC (20.9 [9.6-37.8] ng/ml vs. 6.2 [3.5-9.7] ng/ml, respectively). Active PAI-1 was the best discriminator with an area under the ROC curve and 95% confidence interval (AUROC [95%CI]) of 0.84 [0.79-0.90] compared to 0.75 [0.68-0.72] for PAI-1:t-PA, 0.65 [0.58-0.73] for PAI-1 antigen, 0.62 [0.54-0.69] for AP-TAFI and 0.51 [0.44-0.59] for intact TAFI. Using ROC analysis, we defined an optimal cut-off of 12.8 ng/ml for active PAI-1, with corresponding sensitivity of 71 [61–79] % and specificity of 89 [82–94] %. A lack of association with the time between VTE event and sample collection or with the intake of anticoagulant treatment suggests that active PAI-1 levels are sustainable high in VTE patients.Conclusions
This case–control study emphasizes the clinical importance of measuring active PAI-1 instead of PAI-1 antigen and identifies active PAI-1 as a potential marker of VTE. Prognostic studies will need to address the clinical significance of active PAI-1 as biomarker. 相似文献10.