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PubMed2000

Policy implications of the biological model of mental disorder.

The current dominant paradigm of mental disorder is that psychopathology is a deviation from normal physiological functioning of the brain. This paradigm is closely allied to the identity theory of mind in philosophy, which holds that mental phenomena are identical with the physical state of the brain. The assumptions of the biological model have policy implications, regardless of the utility or 'truth' of the paradigm, which should be made explicit for the assessment of ethics in mental health policy formulation. The nature of mental phenomena has been debated throughout history, without consensus. Several critiques of the biological model are offered to encourage enquiring scepticism. The policy implications discussed are political conservatism, broadened rationales for forced treatment, utility in managed care, and the use of medical necessity criteria to allocate treatment.

Commitment of Persons with Psychiatric Disorders↗
PubMed2002

Computer simulation studies of model biological membranes.

This Account is focused on computer simulation studies of model biological membrane systems with potential applications in biomedical research. In the past decade, classical molecular dynamics has provided novel insights into the properties of model biomembrane systems, including the nature of the DNA-lipid interactions, the effect of pore-forming transmembrane peptides on the lipid environment, and the partitioning of volatile anesthetic molecules. Such simulations, employing full atomic detail, are typically restricted to systems of dimensions less than approximately 10 nm. Simplified models of the coarse-grain type have been intended to bridge the gap between full atomistic detail and the mesoscopic (micron) regime. The use of such models is illustrated with the example of anesthetics in a phospholipid bilayer.

Anesthetics↗
PubMed2006

Modelling biological processes under anaerobic conditions through integrating titrimetric and off-gas measurements-applied to EBPR systems.

An innovative method for modelling biological processes under anaerobic conditions is presented and discussed. The method is based on titrimetric and off-gas measurements. Titrimetric data is recorded as the addition rate of hydroxyl ions or protons that is required to maintain pH in a bioreactor at a constant level. An off-gas analysis arrangement measures, among other things, the transfer rate of carbon dioxide. The integration of these signals results in a continuous signal which is solely related to the biological reactions. When coupled with a mathematical model of the biological reactions, the signal allows a detailed characterisation of these reactions, which would otherwise be difficult to achieve. Two applications of the method to the enhanced biological phosphorus removal processes are presented and discussed to demonstrate the principle and effectiveness of the method.

Bacteria, Anaerobic↗
PubMed2005

Toxicity of the ammonium nitrate NH4NO3 on the respiratory metabolism of three biological models: parameciums, mosses and lichens.

The inopportune throws out of diverse substances in the atmosphere, constitutes without any doubt the obvious of environmental pollution by man. Among these substances, we are interested in the ammonium nitrate NH4NO3, nitrate fertilizers widely used in farming in our region - Annaba located in the eastern part of Algeria - and manufactured in the same region. In fact, the excessive fertilization, the intensive spreading of animal faeces and the industrial pollution are the accumulation sources of nitrate in vegetables, drilling and the underground waters. The goal of this study is to show the obviousness of a possible toxic effect of NH4NO3 on paramecium an inferior plants resed as biological models. The tests of toxicity were achieved on samples of the area of culture of parameciums. Four concentrations were chosen: 10, 20, 30 and 40 mM, and added before and after appearance of the parameciums in the area. The prepared solutions with the same concentrations of NH4NO3, were used for the dampening of the samples of mosses and lichens. The use of an original technique the polarography allowed us to measure the quantity of oxygen consumed by the organisms in presence of the polluent. The results show that: (i): The treatment by NH4NO3 stimulates the respiratory metabolism of paramecium, (ii): with mosses as well as the measure of the consumption of the oxygen shous the abviousness contrasted with a dampening of respiration but also of the photosynthesis. The perturbation of the respiration and photosynthesis of mousses and lichens can explain the degradation of the plant material and the disappearance of certain species from our ecosystem.

Animals↗
PubMed2001

[Keratin 5-positive cells in the breast are progenitor cells of glandular and myoepithelial differentiation. A cell biological model as a basis of breast pathology].

In the present computer-assisted labelling study we demonstrate for the first time that in normal breast tissue keratin (K) 5+ progenitor cells give rise to either glandular (K 8/18+) or to myoepithelial cells (sm-actin = SMA+) via intermediary cells (either K 5/6+; K 8/18+ or K 5/6+; SMA+). Furthermore we have conclusive evidence that benign proliferative breast disease lesions are progenitor cell-derived lesions. In contrast, most breast cancers appear to evolve from glandularly differentiated cells. Western blotting experiments which show large amounts of K 5 in benign proliferative breast lesions, but not in ductal carcinoma in situ confirm the immunofluorescence data. Our results pave the way towards a new cell biological model of breast regeneration, benign proliferative breast disease and breast cancer.

Biomarkers↗
PubMed1996

[3H]dofetilide binding: biological models that manifest solely the high or the low affinity binding site.

Dofetilide is a Class III antiarrhythmic agent known to selectively block the rapid component of the delayed rectifier K+ current (IKr). [3H]Dofetilide binds to a low and a high affinity sites on guinea-pig myocytes. The purposes of this study were: (1) to find biological models which express solely the high or the low [3H]dofetilide binding sites; (2) to characterize the single binding site models; and (3) to establish which of the high or the low affinity binding sites is associated with IKr. We compared and characterized the [3H]dofetilide binding on guinea-pig myocytes, neonatal mouse ventricular homogenate and untransfected CHO cells. These tissue preparations were selected since the neonatal mouse tissue expresses IKr while this current is absent from CHO cells. We compared the IC50 concentrations of dofetilide and two other known IKr blockers E-4031 and sotalol, on [3H]dofetilide binding to these three preparations. Using steady-state and kinetic binding techniques, we characterized the interaction of E-4031 and sotalol with the high and the low [3H]dofetilide binding sites. We found that neonatal mouse ventricle manifest solely the high affinity site (Kd 20 +/- 4 nmol/l, Bmax 18 +/- 4 fmol/mg) while CHO cells manifest solely the low affinity binding site (Kd 1.6 +/- 0.1 mumol/l, Bmax 5.8 +/- 0.8 pmol/mg). We demonstrated that the high and low affinity binding sites present on guinea-pig myocytes show characteristics similar to the single high affinity site expressed on neonatal mouse homogenate and to the single low affinity site expressed on CHO cells, respectively. Class III antiarrhythmic drugs inhibited binding to the high affinity site at concentrations similar to those required to inhibit 50% of IKr current in electrophysiologic studies. In contrast, dofetilide and E-4031 inhibited [3H]dofetilide binding to the low affinity site only at supra-pharmacologic concentrations. We next demonstrated that Class III drugs interact in a competitive manner with the high affinity site on neonatal mouse tissue while they interact with a site allosterically coupled to the low binding site on CHO cells. These data suggest that dofetilide interacts with the high and low affinity sites in a fundamentally different manner. We defined biological models which express solely the high or low [3H]dofetilide binding sites. Only the high affinity site is related to IKr.

Animals↗
PubMed2002

A biological model of tamponade gases following pneumatic retinopexy.

PURPOSE: Predict the persistence and expansion of intra-ocular tamponade gases used in retinal detachment surgery. Quantify factors that contribute to elevations in the intraocular pressure. METHODS: We developed a non-equilibrium physiological model of intraocular gas transfer in vitreoretinal surgery. The model was calibrated using published volumetric decay measurements for four perfluorocarbon gases (CF(4), C(2)F(6), C(3)F(8), C( 4)F(10)) injected into the New Zealand red rabbit. We validated the model by comparing predicted and experimental results at different conditions in the rabbit. Using the rabbit results, the model was scaled up to humans. RESULTS: Predictions of gas expansion, half-life, and intraocular pressure in humans were found to correlate very well with clinical results. Gas transfer in the eye was controlled by diffusion through plasma and membranes. Although intraocular pressure depended on several complicating factors such as the physiological condition of the eye as well as the medications being used, prediction of conditions that favor elevations in intraocular pressure were identified based on the transport and thermodynamic properties of the gases. CONCLUSIONS: The biological model accurately predicted the dynamics of intraocular gases in the human eye. The major factor affecting the intraocular pressure was the aqueous humor dynamics, which is highly dependent on the physiological conditions in the eye. However, for long duration gases such as perfluoropropane, elevations in intraocular pressure are possible following an increase in volume and/or purity of the injected gas. By injecting a mixture of air with an expansive gas, it is possible to reduce elevations in intraocular pressure in patients with the trade off of a reduced longevity of the gas bubble. For gases that diffuse faster than perfluoropropane, there are minimal effects on intraocular pressure due to these changes.

Animals↗
PubMed2004

[Primary cultures of human umbilical chord vein endothelial cells: a biological model for studying enterococcal infection mechanisms].

Although enterococcus bacteria are normal human intestinal flora, they rank as the third most common pathogen involved in hospital acquired infections. Generally, these bacteria are considered extracellular pathogens; however, an increasing number of reports indicate invasiveness to epithelial cell lines and macrophages. Despite their importance as nosocomial infection agents in patients suffering bacteremias and endocarditis, their interaction with endothelial cells has not been fully described. Herein, the nosocomial Enterococcus faecalis isolate Ef2890 from a hospitalized patient was exposed to cultured human venous endothelial cells from the umbilical chord. When the primary cell cultures were inoculated with Ef2890 and treated with bactericidal antibiotics to kill extracellular and adhered bacteria, intracellular bacteria were recovered and plated 4 h post-infection. These observations indicate that cell cultures provide a valuable biological model to study interactions between endothelium and enterococci.

Cells, Cultured↗
PubMed2003

From biological models to the evolution of robot control systems.

Attempts to formulate realistic models of the development of the human oculomotor control system have led to the conclusion that evolutionary factors play a crucial role. Moreover, even rather coarse simulations of the biological evolutionary processes result in adaptable control systems that are considerably more efficient than those designed by human researchers. In this paper I shall describe some of the aspects of these biological models that are likely to be useful for building robot control systems. In particular, I shall consider the evolution of appropriate innate starting points for learning/adaptation, patterns of learning rates that vary across different system components, learning rates that vary during the system's lifetime, and the relevance of individual differences across the evolved populations.

Adaptation, Physiological↗
PubMed1993

Measurement of nitric oxide in biological models.

Nitric oxide (NO) is a small, gaseous, paramagnetic radical with a high affinity for interaction with ferrous hemoproteins such as soluble guanylate cyclase and hemoglobin. Interest in NO measurement increased exponentially with the discovery that NO or a related compound is the endothelium-derived relaxing factor (EDRF). In addition to being a potent endogenous vasodilator, NO has a role in inflammation, thrombosis, immunity, and neurotransmission. Measurement of NO is important as many of its effects (e.g., vasodilatation, inhibition of platelet aggregation) are similar to those of other substances produced by the endothelium, such as prostacyclin. NO is formed in small amounts in vivo and is rapidly destroyed by interaction with oxygen, making measurement difficult. A computerized search of the past five year's literature found NO measurements reported in fewer than 50 of 955 articles dealing with EDRF. Inhibitors of NO synthesis such as the arginine analogs or agents that inactivate NO, such as reduced hemoglobin, are commonly used as specific probes for NO, in vivo and in vitro; however, none of the NO inhibitors is completely specific. The most widely used assays use one of three strategies to detect NO: 1) NO is "trapped" by nitroso compounds, or reduced hemoglobin, forming a stable adduct that is detected by electron paramagnetic resonance (EPR) (detection threshold approximately 1 nmol); 2) NO oxidizes reduced hemoglobin to methemoglobin, which is detected by spectrophotometry (detection threshold approximately 1 nmol); 3) NO interacts with ozone producing light, "chemiluminescence" (detection threshold approximately 20 pmol). These assays can be performed to exclusively detect NO, or by adding acid and reducing agents to the sample, can measure NO and related oxides of nitrogen such as nitrite. Several new amperometric microelectrode assays offer the potential to measure smaller amounts of NO (10(-20) M), permitting NO measurement in intact issues and from single cells. This review describes the pharmacology and toxicology of NO and reviews the major techniques for measuring NO in biological models.

Animals↗
PubMed1990

Transient response of a solid-liquid model biological fluidised bed to a step change in fluid superficial velocity.

The evolution of a solid-liquid model biological fluidised bed under a step change in fluid superficial velocity is described. During a transient step change, the fluidised bed divides into a top zone which remains at the initial porosity and a bottom zone which settles at the final porosity. The interface of discontinuity in porosity moves progressively upwards through the fluidised bed. The velocity at which the top of the fluidised bed expands or contracts and the upward velocity of the porosity transition interface depend only upon the initial and final states of the bed porosity and the fluid superficial velocity. This results in a linear evolution with time of the total bed height and the height of porosity transition interface. The proposed model is well suited to describe the transient response of low-density particles in a fluidised bed, such as encountered in biological systems, to a sudden change of liquid superficial velocity. The model was validated experimentally.

Biomedical Engineering↗
PubMed1985

Efflux of preloaded iodide from the thyroid induced by externally added iodide. A study using a biological model of the thyroid iodide transport system.

Efflux of preloaded I- from the thyroid induced by externally added I- was studied using a biological model of the thyroid I- transport system. Phospholipid vesicles (P-vesicles) made from thyroid plasma membranes and soybean phospholipids were capable of accumulating I- in the presence of external Na+. P-vesicles incubated in 136 mM Na+ containing 0.9 microM I- with 125I- for 2 min accumulated I- so that the I- concentration in the vesicles became about 2 microM. Addition of 5-20 microM stable I- to the incubation mixture at 2 min incubation resulted in a dose-dependent decrease in previously loaded 125I- in the vesicles. In other words, a dose-dependent increase in efflux of preloaded 125I- was observed. While the efflux occurred, Na+-dependent I- influx into P-vesicles was preserved. When 2 mM ClO4-, a specific inhibitor of Na+-dependent I- influx, was added together with 10 microM I-, the external I- failed to diminish preloaded 125I- in P-vesicles. The 125I- efflux did not occur when a large amount of stable I- entered P-vesicles independently of Na+ in the presence of ClO4-. Similar 125I- efflux induced by externally added 5 microM SCN- was also blocked by simultaneously added ClO4-. These observations suggest that such I- efflux from the thyroid is a certain type of uphill I- transport which is closely related to Na+-dependent I- transport and that ClO4- and SCN- act on a common site of the I- transport system.

Animals↗
PubMed2004

Probabilistic methods for addressing uncertainty and variability in biological models: application to a toxicokinetic model.

Population variability and uncertainty are important features of biological systems that must be considered when developing mathematical models for these systems. In this paper we present probability-based parameter estimation methods that account for such variability and uncertainty. Theoretical results that establish well-posedness and stability for these methods are discussed. A probabilistic parameter estimation technique is then applied to a toxicokinetic model for trichloroethylene using several types of simulated data. Comparison with results obtained using a standard, deterministic parameter estimation method suggests that the probabilistic methods are better able to capture population variability and uncertainty in model parameters.

Animals↗
PubMed2004

Simulation as experiment: a philosophical reassessment for biological modeling.

Some scientific modelers suggest that complex simulation models that mimic biological processes should have a limited place in ecological and evolutionary studies. However, complex simulation models can have a role that is different from that of simpler models that are designed to be fit to data. Simulation can be viewed as another kind of experimental system and should be analyzed as such. Here, I argue that current discussions in the philosophy of science and in the physical sciences fields about the use of simulation as an experimental system have important implications for biology, especially complex sciences such as evolution and ecology. Simulation models can be used to mimic complex systems, but unlike nature, can be manipulated in ways that would be impossible, too costly or unethical to do in natural systems. Simulation can add to theory development and testing, can offer hypotheses about the way the world works and can give guidance as to which data are most important to gather experimentally.

Journal Article↗
PubMed2006

Modeling biological rhythms in failure time data.

BACKGROUND: The human body exhibits a variety of biological rhythms. There are patterns that correspond, among others, to the daily wake/sleep cycle, a yearly seasonal cycle and, in women, the menstrual cycle. Sine/cosine functions are often used to model biological patterns for continuous data, but this model is not appropriate for analysis of biological rhythms in failure time data. METHODS: We adapt the cosinor method to the proportional hazards model and present a method to provide an estimate and confidence interval of the time when the minimum hazard is achieved. We then apply this model to data taken from a clinical trial of adjuvant of pre-menopausal breast cancer patients. RESULTS: The application of this technique to the breast cancer data revealed that the optimal day for pre-resection incisional or excisional biopsy of 28-day cycle (i. e. the day associated with the lowest recurrence rate) is day 8 with 95% confidence interval of 4-12 days. We found that older age, fewer positive nodes, smaller tumor size, and experimental treatment were predictive of longer relapse-free survival. CONCLUSION: In this paper we have described a method for modeling failure time data with an underlying biological rhythm. The advantage of adapting a cosinor model to proportional hazards model is its ability to model right censored data. We have presented a method to provide an estimate and confidence interval of the day in the menstrual cycle where the minimum hazard is achieved. This method is not limited to breast cancer data, and may be applied to any biological rhythms linked to right censored data.

Journal Article↗
PubMed1993

Cellular automata approaches to biological modeling.

We review a number of biologically motivated cellular automata (CA) that arise in models of excitable and oscillatory media, in developmental biology, in neurobiology, and in population biology. We suggest technical and theoretical arguments that permit greater speed and enhanced realism, and apply these to several classical examples of pattern formation. We also describe CA that arise in models for fibroblast aggregation, branching networks, trail following, and neuronal maps.

Allergy and Immunology↗
PubMed1990

Biological model for the in vivo measurement of rate of serotonin synthesis in the brain.

A biological model for the measurement of the rate of serotonin synthesis in rat brain with alpha-[14C]methyl-L-tryptophan is described. The rate of serotonin synthesis in several grossly dissected brain structures is reported. The half-life of the precursor pool, estimated from kinetic data, is between 20 and 25 min. The method allows, for the first time, measurement of the brain serotonin synthesis rate without any pharmacological manipulation and does not require separation of metabolites. Autoradiographic data are also presented to demonstrate anatomical resolution of this method. The synthesis rate can be estimated in a large number of discrete structures when autoradiography is applied. Long retention of the tracer in brain is also demonstrated.

Animals↗