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At least 73 records · Page 4Linked to original sources
PubMed2000

Normal tissue complication probabilities: dependence on choice of biological model and dose-volume histogram reduction scheme.

PURPOSE: To evaluate the impact of dose-volume histogram (DVH) reduction schemes and models of normal tissue complication probability (NTCP) on ranking of radiation treatment plans. METHODS AND MATERIALS: Data for liver complications in humans and for spinal cord in rats were used to derive input parameters of four different NTCP models. DVH reduction was performed using two schemes: "effective volume" and "preferred Lyman". DVHs for competing treatment plans were derived from a sample DVH by varying dose uniformity in a high dose region so that the obtained cumulative DVHs intersected. Treatment plans were ranked according to the calculated NTCP values. RESULTS: Whenever the preferred Lyman scheme was used to reduce the DVH, competing plans were indistinguishable as long as the mean dose was constant. The effective volume DVH reduction scheme did allow us to distinguish between these competing treatment plans. However, plan ranking depended on the radiobiological model used and its input parameters. CONCLUSIONS: Dose escalation will be a significant part of radiation treatment planning using new technologies, such as 3-D conformal radiotherapy and tomotherapy. Such dose escalation will depend on how the dose distributions in organs at risk are interpreted in terms of expected complication probabilities. The present study indicates considerable variability in predicted NTCP values because of the methods used for DVH reduction and radiobiological models and their input parameters. Animal studies and collection of standardized clinical data are needed to ascertain the effects of non-uniform dose distributions and to test the validity of the models currently in use.

Animals↗
PubMed1985

2H NMR evidence for antibiotic-induced cholesterol immobilization in biological model membranes.

The interaction of the polyene antibiotic filipin with membrane sterols has been studied by deuterium nuclear magnetic resonance of the molecular probes [2,2,3,4,4,6-2H6]cholesterol and 1-myristoyl-2-[4',4',14',14',14'-2H5]myristoyl-sn-glycero-3-phospho- choline. At physiological temperatures, there is evidence of filipin-induced cholesterol immobilization in the membrane. The 2H NMR spectra of cholesterol show two domains in which ordering and dynamics are very different. In one of these, cholesterol is static on the 2H NMR time scale, whereas in the other it undergoes rapid axially symmetric motions similar to those it exhibits in the drug-free membrane; this indicates that the jumping frequency of cholesterol between the labile and immobilized domains is less than 10(5) s-1. The distribution of cholesterol between these two sites is temperature dependent; at 0 degrees C all sterol molecules are immobilized, whereas at 60 degrees C they are almost totally in the labile site. In contrast to cholesterol, the phospholipids sense only one type of environment, at both the top and center of the bilayer, indicating that cholesterol acts as a screen, preventing the lipids from direct interaction with the antibiotic. At low temperature, the ordering of the lipid in the presence of cholesterol does not change upon filipin addition, whereas at elevated temperatures the local ordering of both the lipid and the labile cholesterol is significantly lower than that in the absence of the drug. Moreover, there is a very important difference between the degree of local ordering as measured by the lipids and by cholesterol at high temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol↗
PubMed2006

Insights into the behaviour of systems biology models from dynamic sensitivity and identifiability analysis: a case study of an NF-kappaB signalling pathway.

Mathematical modelling offers a variety of useful techniques to help in understanding the intrinsic behaviour of complex signal transduction networks. From the system engineering point of view, the dynamics of metabolic and signal transduction models can always be described by nonlinear ordinary differential equations (ODEs) following mass balance principles. Based on the state-space formulation, many methods from the area of automatic control can conveniently be applied to the modelling, analysis and design of cell networks. In the present study, dynamic sensitivity analysis is performed on a model of the IkappaB-NF-kappaB signal pathway system. Univariate analysis of the Euclidean-form overall sensitivities shows that only 8 out of the 64 parameters in the model have major influence on the nuclear NF-kappaB oscillations. The sensitivity matrix is then used to address correlation analysis, identifiability assessment and measurement set selection within the framework of least squares estimation and multivariate analysis. It is shown that certain pairs of parameters are exactly or highly correlated to each other in terms of their effects on the measured variables. The experimental design strategy provides guidance on which proteins should best be considered for measurement such that the unknown parameters can be estimated with the best statistical precision. The whole analysis scheme we describe provides efficient parameter estimation techniques for complex cell networks.

I-kappa B Kinase↗
PubMed2003

A biologic model for assessment of osseous strain patterns and plating systems in the human maxilla.

PURPOSE: This study was conducted to examine a biomechanical model and to help answer fundamental questions that relate to rigid plate fixation in the maxilla. Specifically, we sought to elucidate the principal strain patterns generated in the maxilla secondary to masticatory forces as well as the amount of permanent deformational changes incurred due to these loading forces. MATERIALS AND METHODS: Cadaveric heads with the mandible removed were defleshed and placed in a 2-part testing rig to hold and position the skull for testing in a standard material testing system. Rosette strain gages were attached at predefined points on the skull, and an Instron machine was used to load the skull through the loading port on the tray. A Le Fort I osteotomy was then performed on the skull, and a Walter Lorenz Ultra-Micro plating system was applied by a surgeon to reconnect the upper jaw. A 2-mm gap was left at the line of the osteotomy, and a transducer was attached to measure closure of the gap. Again the skull was loaded with the Instron (Canton, MA) machine. RESULTS: The results indicate a linear relationship exists with both maximum (tensile) and minimum (compressive) strain patterns relative to incremental load placement on the intact maxilla. The strain patterns after the Le Fort I osteotomy and plating were different and less linear. The differential variable reluctance transducer data showed a low rate of closure or transient increase in the gap at low loads (0 to 15 kilopond [kp] range) and a steeper slope of closure during high loads (15 to 60 kp range). It is also evident that axial loading forces cause permanent deformation and failure of osseous plating systems predominantly through bending. CONCLUSIONS: This model provides a foundation of knowledge regarding biomechanical strains in the maxilla subjected to static compressive loads in the force range of mastication. In addition, it serves as a comparative reference to assess rigidity of various craniofacial plating systems and to validate proposed standardized synthetic models. With the advent of increasingly precise surgery and new plating systems, this model can be used to help guide placement and design of plating systems; thereby allowing for ideal stabilization and optimizing surgical outcome.

Aged↗
PubMed1986

Exemplar reasoning about biological models and diseases: a relation between the philosophy of medicine and philosophy of science.

This paper discusses the structure of medical science with a special focus on the role of generalizations and universals in medicine, and philosophy of medicine's relation with the philosophy of science. I argue that a usually overlooked aspect of Kuhnian paradigms, namely, their characteristic of being "exemplars", is of considerable significance in the biomedical sciences. This significance rests on certain important differences from the physical sciences in the nature of theories in the basic and the clinical medical sciences. I describe those differences and maintain that they are these differentiating features that require the use of more comparative and analogical reasoning in medicine. I suggest that Kitcher's recent introduction of the notion of a 'practice' may have similar implications if it is construed to contain more analogical elements than he appears to recognize in his initial formulation. Finally I argue that though Gorovitz and MacIntyre's characterization of medicine as a "science of particulars" bears some similarities with my thesis, I maintain that such a position without careful qualification can lead to ignoring both the nature of generalizations in these sciences and their role as positive analogies tying together a family of overlapping models.

Humans↗
PubMed1988

Adsorption of benzo(a)pyrene on to asbestos and manmade mineral fibres in an aqueous solution and in a biological model solution.

The adsorption of benzo(a)pyrene (BaP) on to three types of asbestos (chrysotile antophyllite, and amosite) and three types of manmade mineral fibres (MMMF) (rock wool, slag wool, and glass wool) in a physiological water solution was studied. Adsorption was determined from the decrease in the liquid concentration of BaP on the addition of the solid material. Results show that all the fibres weakly adsorb BaP, approximately within the same order of magnitude. The combined adsorption of BaP and phosphatidylcholine (PC) on to chrysotile and amosite asbestos and on to rock wool in aqueous solution was also studied. PC, one of the major constituents in lung surfactant, forms a separate lipid phase in water consisting of micellar liposomes or lipid bilayers. A decrease in the liquid concentration of PC was found when any of the three materials was added, indicating adsorption of the lipid phase on to the fibres. A coincident decrease in the liquid concentration of BaP was also found indicating that BaP is readily solubilised in PC and will accompany the adsorption of this compound on to the fibres. Owing to the high lipid aqueous partition coefficient of BaP, it is concluded that the direct adsorption of BaP on to the fibres will be negligible when PC is present in the system even at low concentrations. Phospholipid adsorption by the fibres and not their direct adsorption of aromatic hydrocarbons should therefore be the crucial parameter for this indirect interaction between fibres and aromatic hydrocarbons.

Adsorption↗
PubMed1999

Balanced macrophage activation hypothesis: a biological model for development of drugs targeted at macrophage functional states.

Macrophages play a central role in the immune response and are major targets for chronic infection with viruses such as HIV. Recent studies on macrophage differentiation have shown the existence of classical activation and the counter-balancing anti-inflammatory alternative activation states. In the 'balanced macrophage activation hypothesis' we propose that macrophage activation is a cyclic process that balances these two states to achieve proper immunologic function. Dysregulation of this cycle would, therefore, be associated with various forms of chronic disease. This model has been utilized in the drug development of WF10, a novel macrophage-targeted drug, currently in advanced clinical testing for the treatment of HIV disease.

Antigen Presentation↗