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1.
Conclusion: Medical decisions concerning the end of life are a difficult matter and they evoke much emotional response. What is needed, however, is an open debate in order to improve the moral quality of decision making, not "dances with data". The central question in this debate should be, as Callahan aptly notes, whether medicine should involve itself only in that kind of "suffering which is brought on by illness and dying as biological phenomena" (emphasis added) or whether it should concern itself with the wellbeing of the patient. Apart from the fundamental question as to what types of suffering are to be considered as, at least in part biological phenomena, in The Netherlands most doctors, ourselves included, think the medical profession should do the latter. 相似文献
2.
Bouma B Kroon-Batenburg LM Wu YP Brünjes B Posthuma G Kranenburg O de Groot PG Voest EE Gebbink MF 《The Journal of biological chemistry》2003,278(43):41810-41819
Amyloid fibrils are components of proteinaceous plaques that are associated with conformational diseases such as Alzheimer's disease, transmissible spongiform encephalopathies, and familial amyloidosis. Amyloid polypeptides share a specific quarternary structure element known as cross-beta structure. Commonly, fibrillar aggregates are modified by advanced glycation end products (AGE). In addition, AGE formation itself induces protein aggregation. Both amyloid proteins and protein-AGE adducts bind multiligand receptors, such as receptor for AGE, CD36, and scavenger receptors A and B type I, and the serine protease tissue-type plasminogen activator (tPA). Based on these observations, we hypothesized that glycation induces refolding of globular proteins, accompanied by formation of cross-beta structure. Using transmission electron microscopy, we demonstrate here that glycated albumin condensates into fibrous or amorphous aggregates. These aggregates bind to amyloid-specific dyes Congo red and thioflavin T and to tPA. In contrast to globular albumin, glycated albumin contains amino acid residues in beta-sheet conformation, as measured with circular dichroism spectropolarimetry. Moreover, it displays cross-beta structure, as determined with x-ray fiber diffraction. We conclude that glycation induces refolding of initially globular albumin into amyloid fibrils comprising cross-beta structure. This would explain how glycated ligands and amyloid ligands can bind to the same multiligand "cross-beta structure" receptors and to tPA. 相似文献
3.
Kater L Houtepen R De Vries R Widdershoven G 《Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences》2003,34(4):669-684
Over the past three or four decades, the concept of medical ethics has changed from a limited set of standards to a broad field of debate and research. We define medical ethics as an arena of moral issues in medicine, rather than a specific discipline. This paper examines how the disciplines of health care ethics and health care law have developed and operated within this arena. Our framework highlights the aspects of jurisdiction (Abbott) and the assignment of responsibilities (Gusfield). This theoretical framework prompted us to study definitions and changing responsibilities in order to describe the development and interaction of health care ethics and health law. We have opted for the context of the Dutch debate about end-of-life decisions as a relevant case study. We argue that the specific Dutch definition of euthanasia as 'intentionally taking the life of another person by a physician, upon that person's request' can be seen as the result of the complex jurisdictional process. This illustrates the more general conclusion that the Dutch debate on end-of-life decisions and the development of the two disciplines must be understood in terms of mutual interaction. 相似文献
4.
The relationship between cellular metabolism and the cell cycle machinery is by no means unidirectional. The ability of a cell to enter the cell cycle critically depends on the availability of metabolites. Conversely, the cell cycle machinery commits to regulating metabolic networks in order to support cell survival and proliferation. In this review, we will give an account of how the cell cycle machinery and metabolism are interconnected. Acquiring information on how communication takes place among metabolic signaling networks and the cell cycle controllers is crucial to increase our understanding of the deregulation thereof in disease, including cancer. 相似文献
5.
Derikx LC Vis R Meinders T Verdonschot N Tanck E 《Computer methods in biomechanics and biomedical engineering》2011,14(2):183-193
Although asymmetric yielding in bone is widely shown in experimental studies, previous case-specific non-linear finite element (FE) studies have mainly adopted material behaviour using the Von Mises yield criterion (VMYC), assuming equal bone strength in tension and compression. In this study, it was verified that asymmetric yielding in FE models can be captured using the Drucker-Prager yield criterion (DPYC), and can provide better results than simulations using the VMYC. A sensitivity analysis on parameters defining the DPYC (i.e. the degree of yield asymmetry and the yield stress settings) was performed, focusing on the effect on bone failure. In this study, the implementation of a larger degree of yield asymmetry improved the prediction of the fracture location; variations in the yield stress mainly affected the predicted failure force. We conclude that the implementation of asymmetric yielding in case-specific FE models improves the prediction of femoral bone strength. 相似文献
6.
Nesmelova IV Sham Y Dudek AZ van Eijk LI Wu G Slungaard A Mortari F Griffioen AW Mayo KH 《The Journal of biological chemistry》2005,280(6):4948-4958
The apparent complexity of biology increases as more biomolecular interactions that mediate function become known. We have used NMR spectroscopy and molecular modeling to provide direct evidence that tetrameric platelet factor-4 (PF4) and dimeric interleukin-8 (IL8), two members of the CXC chemokine family, readily interact by exchanging subunits and forming heterodimers via extension of their antiparallel beta-sheet domains. We further demonstrate using functional assays that PF4/IL8 heterodimerization has a direct and significant consequence on the biological activity of both chemokines. Formation of heterodimers enhances the anti-proliferative effect of PF4 on endothelial cells in culture, as well as the IL8-induced migration of CXCR2 vector-transfected Baf3 cells. These results suggest that CXC chemokine biology, and perhaps cytokine biology in general, may be functionally modulated at the molecular level by formation of heterodimers. This concept, in turn, has implications for designing chemokine/cytokine variants with modified biological properties. 相似文献
7.
The accuracy of measuring the kinematics of rising from a chair with accelerometers and gyroscopes 总被引:8,自引:0,他引:8
Boonstra MC van der Slikke RM Keijsers NL van Lummel RC de Waal Malefijt MC Verdonschot N 《Journal of biomechanics》2006,39(2):354-358
The purpose of this study was to assess the accuracy of measuring angle and angular velocity of the upper body and upper leg during rising from a chair with accelerometers, using low-pass filtering of the accelerometer signal. Also, the improvement in accuracy of the measurement with additional use of high-pass filtered gyroscopes was assessed. Two uni-axial accelerometers and one gyroscope (DynaPort) per segment were used to measure angles and angular velocities of upper body and upper leg. Calculated angles and angular velocities were compared to a high-quality optical motion analysis system (Optotrak), using root mean squared error (RMS) and correlation coefficient (r) as parameters. The results for the sensors showed that two uni-axial accelerometers give a reasonable accurate measurement of the kinematics of rising from a chair (RMS = 2.9, 3.5, and 2.6 degrees for angle and RMS = 9.4, 18.4, and 11.5 degrees /s for angular velocity for thorax, pelvis, and upper leg, respectively). Additional use of gyroscopes improved the accuracy significantly (RMS = 0.8, 1.1, and 1.7 degrees for angle and RMS = 2.6, 4.0 and 4.9 degrees /s for angular velocity for thorax, pelvis and upper leg, respectively). The low-pass Butterworth filter had optimal cut-off frequencies of 1.05, 1.3, and 1.05 for thorax, pelvis, and upper leg, respectively. For the combined signal, the optimal cut-off frequencies were 0.18, 0.2, and 0,38 for thorax, pelvis and upper leg, respectively. The filters showed no subject specificity. This study provides an accurate, inexpensive and simple method to measure the kinematics of movements similar to rising from a chair. 相似文献
8.
Huber H Chen X Hendriks M Keijsers D Voesenek LA Pierik R Poorter H de Kroon H Visser EJ 《The New phytologist》2012,194(2):572-582
Plants may experience different environmental cues throughout their development which interact in determining their phenotype. This paper tests the hypothesis that environmental conditions experienced early during ontogeny affect the phenotypic response to subsequent environmental cues. This hypothesis was tested by exposing different accessions of Rumex palustris to different light and nutrient conditions, followed by subsequent complete submergence. Final leaf length and submergence-induced plasticity were affected by the environmental conditions experienced at early developmental stages. In developmentally older leaves, submergence-induced elongation was lower in plants previously subjected to high-light conditions. Submergence-induced elongation of developmentally younger leaves, however, was larger when pregrown in high light. High-light and low-nutrient conditions led to an increase of nonstructural carbohydrates in the plants. There was a positive correlation between submergence-induced leaf elongation and carbohydrate concentration and content in roots and shoots, but not with root and shoot biomass before submergence. These results show that conditions experienced by young plants modulate the responses to subsequent environmental conditions, in both magnitude and direction. Internal resource status interacts with cues perceived at different developmental stages in determining plastic responses to the environment. 相似文献
9.
Angela van Diepen Cornelis H. Smit Loes van Egmond Narcis B. Kabatereine Angela Pinot de Moira David W. Dunne Cornelis H. Hokke 《PLoS neglected tropical diseases》2012,6(11)
Background
Schistosomiasis (bilharzia) is a chronic and potentially deadly parasitic disease that affects millions of people in (sub)tropical areas. An important partial immunity to Schistosoma infections does develop in disease endemic areas, but this takes many years of exposure and maturation of the immune system. Therefore, children are far more susceptible to re-infection after treatment than older children and adults. This age-dependent immunity or susceptibility to re-infection has been shown to be associated with specific antibody and T cell responses. Many antibodies generated during Schistosoma infection are directed against the numerous glycans expressed by Schistosoma. The nature of glycan epitopes recognized by antibodies in natural schistosomiasis infection serum is largely unknown.Methodology/Principal Findings
The binding of serum antibodies to glycans can be analyzed efficiently and quantitatively using glycan microarray approaches. Very small amounts of a large number of glycans are presented on a solid surface allowing binding properties of various glycan binding proteins to be tested. We have generated a so-called shotgun glycan microarray containing natural N-glycan and lipid-glycan fractions derived from 4 different life stages of S. mansoni and applied this array to the analysis of IgG and IgM antibodies in sera from children and adults living in an endemic area. This resulted in the identification of differential glycan recognition profiles characteristic for the two different age groups, possibly reflecting differences in age or differences in length of exposure or infection.Conclusions/Significance
Using the shotgun glycan microarray approach to study antibody response profiles against schistosome-derived glycan elements, we have defined groups of infected individuals as well as glycan element clusters to which antibody responses are directed in S. mansoni infections. These findings are significant for further exploration of Schistosoma glycan antigens in relation to immunity. 相似文献10.
CJ Zuurbier WM Jong O Eerbeek A Koeman WP Pulskens LM Butter JC Leemans MW Hollmann 《PloS one》2012,7(7):e40643