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At least 415 records · Page 23Linked to original sources
PubMed1992

Correlation between chemical suppression of natural killer cell activity in mice and susceptibility to cytomegalovirus: rationale for applying murine cytomegalovirus as a host resistance model and for interpreting immunotoxicity testing in terms of risk of disease.

The purpose of this study was to determine the relationship between chemical suppression of natural killer (NK) cell activity in mice and chemical effects on susceptibility to murine cytomegalovirus (MCMV) infection. The goal was to provide a rational basis for applying MCMV as a host resistance model for immunotoxicity testing and to provide risk assessors some guidance in relating suppression of NK cell activity to enhanced risk of disease. Data from studies with eight chemicals administered in various doses and by various routes were evaluated, and a significant correlation was observed between chemical suppression of virus-augmented NK cell activity and increased mortality due to MCMV infection. In contrast, effects of the same chemical treatments on spontaneous NK cell activity (i.e., basal activity in uninfected mice) did not correlate with effects of these chemicals on mortality due to MCMV. Although chemicals that suppressed spontaneous NK cell activity enhanced infection, the converse was not always true--that is, increased susceptibility to infection and suppression of virus-augmented NK cell activity were observed on three occasions when spontaneous NK cell activity was unaffected. This latter phenomenon plus the fact that for two chemicals spontaneous NK was suppressed at concentrations twofold below that which affected mortality appear to account for the poor statistical correlation. Nevertheless, the data indicate that MCMV is a useful host resistance model to be applied in immunotoxicity testing when suppression of NK cell activity has been demonstrated. However, virus-augmented activity may be a better indicator than spontaneous activity. The data also indicated that suppression of NK cell activity is predictive of increased susceptibility to infection and hence provides qualitative guidance (hazard identification) to risk assessors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Toxicodynamic modelling and the interpretation of in vitro toxicity data.

The results of in vitro toxicity experiments are not easily extrapolated to 'toxicological risk' for an intact organism. One of the most obvious differences between the situation in vitro and in vivo is the absence of the processes of absorption, distribution, metabolism and excretion that govern the exposure of the target tissues of the organism in vivo. The development of biokinetic models is aimed at estimating the relevant target tissue concentration of a compound. In our study, biokinetic models were constructed, where possible, solely on the basis of in vitro derived parameters for biotransformation as well as on partition coefficients determined or calculated from physicochemical structures. Another requirement is the existence of appropriate in vitro biological systems for the measurement of relevant effects. This requires a thorough knowledge of the possible mechanisms of toxic action, and of the physiology of the target organs. When these prerequisites are met (i.e. when the appropriate parameters can be quantified in a non-animal system), then an estimate of the dynamics in vitro can be made (e.g. as a critical active concentration). This will then result in a model describing a compound's dynamics. Eventually, the result of biokinetic and toxicodynamic models will need to be integrated in a compound's hazard and/or risk evaluation. A study carried out in the ECITTS programme showed promising results for the estimation of the acute and chronic systemic toxicity of a number of neurotoxic compounds.

Acrylamide↗
PubMed1987

[Metabolic models for the interpretation of indirect caloric measurements in intensive care patients].

Precondition for the evaluation of indirect calorimetry data by standard procedures is an undisturbed physiological metabolic situation. Metabolic changes in stress metabolism, which are a reduction of enzyme activity, increased rates of gluconeogenesis und ketogenesis, and simultaneous occurrence of lipolysis and lipogenesis cannot be considered by those calculations. Various problems concerning the evaluation of data obtained on traumatized patients confirm the presumption that standard procedures are not suitable in the case of posttraumatic metabolic disturbances. Therefore, we developed two computer-supported metabolic models, which assume a reduced activity of the three key enzymes: pyruvate dehydrogenase (PDH), phosphofructokinase (PFK) and citrate synthetase (CS). The blocked metabolites are bypassed to gluconeogenesis, lipogenesis and in so called 'pools' ('glucose-pool', 'acetyl-pool'). In addition, a detailed simulation of amino acid degradation is permitted. The models were applied to evaluate indirect calorimetric data of four patients, which could not be evaluated by standard procedures. It was shown that an evaluation of all data was possible by at least one model. All enzymes presented a slight to complete blockade. The calculated maximal activities of PFK was 1.59 mol/d, of PDH 6.31 mol/d and that of CS 6.55 mol/d. These activities were far below the values of normal human beings. As a result of these enzyme inhibitions, high rates of gluconeogenesis (max. 387 g/d) and lipogenesis (max. 511 g/d) as well as high values for the glucose-pool (max. 387 g/d) and the acetyl-pool (max. 641 g/d) were calculated. The interpretation of the pools was difficult. Renal elimination of the metabolites was not found in our patients, an accumulation was impossible for osmotic reasons. Therefore, despite the catabolic hormonal character of stress metabolism, storage as molecules of high molecular weight should be taken into account.

Calorimetry↗
PubMed1993

Interpretation of energy adjustment models for nutritional epidemiology.

The authors discuss the interpretation of three alternative energy adjustment models for nutritional epidemiology. It is shown that four different effects are addressed by these models: 1) adding nutrient N, 2) substituting nutrient N for "other" nutrients, 3) adding "other" nutrients, and 4) adding both N and "other" nutrients in a specific ratio. Each of these effects may be estimated from any of the three models. The relative standard errors for the four estimated effects are also provided.

Diet↗
PubMed1976

The physics of the cranial cavity, hydrocephalus and normal pressure hydrocephalus: mechanical interpretation and mathematical model.

It is intended for this research, to provide some basis for the understanding of the rational mechanics of the cranial content. There are many interesting and controversial facts derived from the experimental and clinical-pathological observations of hydrocephalus and increased intracranial pressure. For instance, in some patients a moderate increase of intracranial pressure is accompanied by hydrocephalus and mental changes, while in others, with high intracranial pressure, the ventricles and mental functions remain unaltered. What then is the parameter that changes the size of the ventricles and impairs brain function? It is shown how the transmission of intraventricular pressure throughout the brain parenchyma creates a stress distribution that varies in magnitude; how during the production, maintenance, and reversal of hydrocephalus, and normal pressure hydrocephalus the stress is distributed throughout the brain; and how in the presence of a sudden increase of intracranial pressure nature has arranged additional mechanisms for protecting the brain. It is important to recognize that some aspects of intracranial physiopathology can be explained through classical concepts of physics, prior to attempting to interpret such processes solely in terms of biological or auto-regulatory phenomena.

Adult↗
PubMed1980

Interpretation by theoretical model of dynamic and steady components in frog gustatory response.

The behavior of dynamic component (slow component) and steady component of the frog glossopharyngeal nerve response to CaCl2, measured in number of impulses firing per second, was examined under various conditions. 1) The magnitude of the dynamic component increased with the flow rate below about 0.3 ml/s, whereas that of the steady component was independent of the flow rate. 2) The magnitude of the dynamic component increased with a rise of temperature between 2.5 and 20 degrees C, whereas that of the steady component was practically independent of temperature. Removal of Ca2+ from the receptor membrane yielded a large dynamic component even at 2.5 degrees C. 3) The treatment of the tongue with procaine led to a large reduction in the magnitude of the dynamic component, whereas the effect of procaine on the steady component was not pronounced. 4) The magnitude of the dynamic component varied with the pH of the stimulating solution, whereas that of steady component was practically independent of a pH between 4.5 and 7.5. The above results were well interpreted by the following reaction scheme: S (stimulus + A (receptor domain) in equilibrium (SA)active in equilibrium (SA) inactive where (SA) active and (SA) inactive are active and inactive complexes.

Action Potentials↗
PubMed1992

Flow cytometric analysis of the cell cycle: mathematical modeling and biological interpretation.

Estimation of the repartition of asynchronous cells in the cell cycle can be explained by two hypotheses: the cells are supposed to be distributed into three groups: cells with a 2c DNA content (G0/1 phase), cells with a 4c DNA content (G2 + M phase) and cells with a DNA content ranging from 2c to 4c (S phase); there is a linear relationship between the amount of fluorescence emitted by the fluorescent probe which reveals the DNA and the DNA content. According to these hypotheses, the cell cycle can be represented by the following equation: [formula: see text] All the solutions for this equation are approximations. Non parametric methods (or graphical methods: rectangle, peak reflect) only use one or two phase(s) of the cell cycle, the remaining phase(s) being estimated by exclusion. In parametric methods (Dean & Jett, Baisch II, Fried), the DNAT(x) distribution is supposed to be known and is composed of two gaussians (representative of G0/1 and G2 + M) and a P(x,y) function representative of S phase. Despite the generality, these models are not applicable to all sample types, particularly heterogeneous cell populations with various DNA content. In addition, the cell cycle is dependent on several regulation points (transition from quiescence to proliferation, DNA synthesis initiation, mitosis induction) and biological perturbations can also lead to cytokinesis perturbations. Before the emergence of flow cytometry, the current view of cell cycle resided in the assessment of cell proliferation (increase in cell number) or the kinetic of molecules incorporation (DNA precursors).(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Cycle↗
PubMed2004

Discrepancies between BOLD and flow dynamics in primary and supplementary motor areas: application of the balloon model to the interpretation of BOLD transients.

The blood-oxygen-level-dependent (BOLD) signal measured in the brain with functional magnetic resonance imaging (fMRI) during an activation experiment often exhibits pronounced transients at the beginning and end of the stimulus. Such transients could be a reflection of transients in the underlying neural activity, or they could result from transients in cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), or cerebral blood volume (CBV). These transients were investigated using an arterial spin labeling (ASL) method that allows simultaneous measurements of BOLD and CBF responses. Responses to a finger-tapping task (40-s stimulus, 80-s rest) were measured in primary motor area (M1) and supplementary motor area (SMA) in five healthy volunteers. In SMA, the average BOLD response was pronounced near the beginning and end of the stimulus, while in M1, the BOLD response was nearly flat. However, CBF responses in the two regions were rather similar, and did not exhibit the same transient features as the BOLD response in SMA. Because this suggests a hemodynamic rather than a neural origin for the transients of the BOLD response in SMA, we used a generalization of the balloon model to test the degree of hemodynamic transients required to produce the measured curves. Both data sets could be approximated with modest differences in the shapes of the CMRO2 and CBV responses. This study illustrates the utility and the limitations of using theoretical models combined with ASL techniques to understand the dynamics of the BOLD response.

Adult↗
PubMed1988

A transmission line modelling approach to the interpretation of uterine Doppler waveforms.

An electrical analogue model of an artery that terminates into a vascular bed is presented. The model consists of an uniform transmission line that represents the artery and a load impedance that represents the vascular bed. The transmission line parameters are based on a well-established first-order approximation of the Navier-Stokes equations for fluid flow in distensible tubes. The model can be used to predict the incident and reflected components of both the arterial pressure and flow waveforms. In addition, it can predict the vessel diameter change and the mean blood velocity waveforms. In this study, the model was applied to the uterine artery so that the characteristics of the utero-placental circulation can be related to Doppler ultrasound recordings. It was found that the presence of the dicrotic notch in the uterine artery time-velocity waveform is the result of wave reflection and that a persistent notch past 20 weeks' gestation may be indicative of an abnormally high placental bed resistance. It is shown that the simulation results are consistent with the known physiological data and the clinically recorded uterine Doppler waveforms.

Arteries↗
PubMed2001

The effects of scrambling on Spanish and Korean agrammatic interpretation: why linear models fail and structural models survive.

Several models of comprehension deficits in agrammatic aphasia rely heavily on linear considerations in the assignment of thematic roles to structural positions (e.g., the Trace-Deletion Hypothesis, the Mapping Hypothesis, and the Argument-Linking Hypothesis). These accounts predict that constructions in languages with rules that affect syntactic structure but preserve relative linear order should be unimpaired. Other models [e.g., the Double-Dependency Hypothesis, (DDH)] do not resort to linearity but are purely structural in conception and therefore should be immune to word-order effects. We tested linear and nonlinear accounts with scrambling structures in Korean and topicalization structures in Spanish. The results are very clear. The (nonlinear) DDH is entirely compatible with the evidence, but the linear accounts are not.

Adult↗
PubMed1990

Cell-cycle independent increase in heat production in response to growth factors in cultured rat fibroblasts: interpretation by continuum model.

We measured the heat output from rat 3Y1 fibroblastic cells by stopped-flow method using a flow microcalorimeter. When the resting cells were stimulated to initiate DNA synthesis with growth factors, the heat output increased. Although cells normally progressed through S and G2 phases in the absence of any growth factor, cells increased the heat output in response to the growth factors during the progression through these phases. These results are consistent with the continuum model in which the preparation for the initiation of S phase occurs continuously and cumulatively between adjacent S phases not restricted in G1 phase.

Animals↗