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Air quality in the vicinity of urban roads.

Motor vehicle emissions are a major source of CO, NOx and lead particulate concentrations to urban air quality. London urban Boroughs with high traffic densities are therefore a particular cause for concern. The air quality was monitored at an urban background site in the London Borough of Haringey for 2-years. The results of this study are assessed and their effect on human health is considered in the light of EC Directives and WHO guidelines. A desk top modelling technique based on Gaussian diffusion theory was used to predict the CO levels found at the background site. All predicted levels had a accuracy of better than 30%.

Air Pollution

In vitro magnesium absorption and the role of intestinal motility.

Magnesium (Mg) is known as an inhibitor of spontaneously contracting muscular tissues. To increase extracellular Mg in vivo, high doses of Mg must be given orally. Therefore, we investigated the effect of different doses of Mg given from the mucosal side of the small intestine of rats. According to the model of Trendelenburg, a system for the perfusion of isolated small intestine was developed, which allows the simultaneous recording of absorption and muscle contractions. Increasing doses of Mg were applied serosally or intraluminally. Intramulinal Mg did not affect intestinal motility. In contrast, increasing concentrations of serosal Mg resulted in a 50% inhibition of motility at 2.9 mmol/l Mg. This indicates no influence on intestinal motility of high doses of Mg acting from the mucosal side. In further studies, the addition of citric acid or taurocholic acid did not alter Mg absorption. Serosally applied amiloride (1 mmol/l) inhibited absorption, but also resulted in complete loss of motility. Since in this model passive diffusion is the most important mechanism of Mg transport, a direct influence of amiloride on Mg absorption can be excluded. From these data, we conclude that intestinal motility influences absorption--also of ions in aqueous solution--and should therefore be taken into account in absorption studies.

Amiloride

Computer simulation of oral fluoride clearance.

The presence of fluoride in saliva and dental plaque is important for prevention of dental caries. The elimination of fluoride from the oral cavity after introduction of a fluoride containing agent is a complicated physiological process. This process was simulated with a Pascal program running under MS-DOS on IBM-compatible microcomputers. The program calculated the fluoride concentration in saliva as a function of time from several input parameters, the most important being the amount of fluoride, salivary stimulation due to the fluoride vehicle, resting salivary flow rate and volume factors. Furthermore, factors such as excretion of fluoride in the saliva following fluoride absorption in the intestinal tract were modeled. The fluoride concentration in dental plaque due to diffusion was also calculated. Output was directed to files which could be processed by a graphics interface. The results of the computations were very similar to findings in vivo.

Algorithms

Pharmacokinetics of halothane in the dog. Comparison of theory and measurement in individuals.

After surgical preparation under pentobarbitone anaesthesia seven dogs of mean body weight 31 kg were ventilated with 1% halothane for 80 min. At 1, 2, 5, 10, 20, 40 and 80 min after the start of the halothane administration blood samples were taken from the femoral artery and pulmonary artery and from a cerebral, a renal and a femoral vein. At 80 min a biopsy sample of skeletal muscle (psoas) was taken. The halothane tension in all samples was determined by extraction into carbon tetrachloride followed by gas chromatographic analysis using chloroform as an internal standard. The measured tensions were compared with tensions computed from a multi-compartment model of the uptake and distribution of halothane in the body. The model was quantified by measurements, in each individual, of total body mass, the masses of the major organs and the solubility of halothane in the major organs and tissues; by measurements of blood volume and solubility in blood at the start and finish of the halothane administration; and by repeated measurements of alveolar ventilation, cardiac output and body temperature. For the original version of the model, the computed tensions deviated from the measured tensions to an extent greater than could be attributed to experimental error and in a manner which could be attributed to metabolism of halothane and probably to direct diffusion of halothane from well-perfused organs and lean tissues into fat. Direct experimental evidence of diffusion into perirenal fat was obtained in supplementary experiments. With the quantitation of the model distorted to mimic the processes of metabolism and diffusion, measured arterial tensions could be predicted with a mean error of -0.2 mm Hg (SD 0.6 mm Hg). The mean measured arterial tension was 3.5 mm Hg.

Animals

The "pump-leak" model and exchange diffusion.

Steady-state concentration gradients across cell membranes have often been attributed to the associated leakage of solute down its electrochemical potential gradient, and active transport at an equal rate in the opposite direction. Several workers have evaluated the minimal energetic requirements of such a "pump-leak" model for sodium in muscle tissue, presuming that influx occurs only via the leak pathway and to no extent by way of the active transport pathway. The high energy requirements so predicted have led to the suggestions that either (a) sodium is not actively transported, being at equilibrium distribution across the cell surface, or (b) substantial sodium movement must be by means of exchange diffusion. The present treatment, based on the consideration that the active transport mechanism is bidirectional, demonstrates that the rates of influx and efflux associated with a given rate of active transport are explicit functions of two parameters: (1) the ratio of the exchange resistance of the active pathway to that of the leak pathway, and (2) the electrochemical potential difference across the cell surface. Lacking precise values for these parameters, the demonstration of a high rate of isotope flux is not compelling evidence either against active transport or for a discrete exchange diffusion mechanism. Various concepts and criteria of exchange diffusion are discussed.

Biological Transport, Active

Axon shape as a basis for multinode functional units in a hierarchical neural model.

The ability of animals to perform fixed action patterns and to access information by categories suggests that there are several types of hierarchical organization in the nervous system. This paper employs data about axon shape and neurotransmitter effect to demonstrate the emergence of hierarchical structure in a neural model. Two dimensions of neural classification, axon shape and neurotransmitter effect, are used to generate a five-node-type neural model. Neurons are classified as interneurons, relay cells, and monoamine transmitters on the basis of axon shape; the transmitter classifications include excitatory, inhibitory, and parameter-changing. The five types of nodes in the model correspond to all the biologically observed combinations: excitatory and inhibitory short-range, excitatory and inhibitory long-range-directional, and long-lasting long-range-diffuse nodes. The emergence of multinode functional units (MFUs) from the five-node-type model is mathematically demonstrated. These units correspond to cortical columns anatomically defined by the axon fields of relay cells, and are called columnar multinode functional units (CMFUs). CMFUs may, in turn, be part of larger functional groups designated coherent populations, which consist of widely distributed CMFUs in retinotopically equivalent locations. The existence of coherent populations imposes a three-level hierarchical structure on the model. To represent this hierarchical structure, a new type of CMFU node, which has a set of vector-valued inputs and outputs, is introduced. Each CMFU node contains a system of short-range nodes which supplies it with vector-valued inputs. Sets of long-range-diffuse nodes are also treated as vector-valued nodes whose outputs control the size and number of coherent populations. The role of coherent populations and hierarchical organization in the nervous system is discussed for such cognitive tasks as visual perception, attention and learning. Physiological and behavioral evidence are cited which support the existence of a similar three-level hierarchy in vertebrate brains.

Animals

Theoretical analysis of net tracer flux due to volume circulation in a membrane with pores of different sizes. Relation to solute drag model.

When osmotic pressure across an artificial membrane, produced by a permeable electrically neutral solute on one side of it, is balanced by an external pressure difference so that there is no net volume flow across the membrane, it has been found that there will be a net flux of a second electrically neutral tracer solute, present at equal concentrations on either side of the membrane, in the direction that the "osmotic" solute diffuses. This has been ascribed to solute-solute interaction or drag between the tracer and the osmotic solutes. An alternative model, presented here, considers the membrane to have pores of different sizes. Under general assumptions, this "heteroporous" model will account for both the direction of net tracer flux and the observed linear dependence of unidirectional tracer fluxes on the concentration of the osmotic solute. The expressions for the fluxes of solutes and solvent are mathematically identical under the two models. An inequality is derived which must be valid if the solute interaction model and/or the heteroporous model can account for the data. If the inequality does not hold, then the heteroporous model alone cannot explain the data. It was found that the inequality holds for most published observations except when dextran is the osmotic solute.

Cell Membrane Permeability

[The application of in vivo diffusion weighted magnetic resonance imaging to intracranial disorders].

We have developed a magnetic resonance (MR) spin echo method to obtain diffusion weighted imaging using motion-probing gradient (MPG) pulses in one or three orthogonal directions before and after a 180 degree pulse. Phantom models containing water and acetone, normal volunteers and patients with brain tumors, brain edema and infarction were examined. Experimental models of brain edema including triethyltin intoxication and cold injuries were also examined in Wistar rats. MRI was performed at a 1.0-T clinical machine or a 4.7-T experimental machine using spin echo pulse sequences with or without additional MPGs on one or three orthogonal axes. The one direction method was useful to define diffusion anisotropy of myelinated axonal fibers in white matter. Faster diffusion was detected in the white matter parallel to the direction of MPGs. On the other hand, slower diffusion was detected perpendicular to the direction of MPGs because the myelin sheath restricted water diffusion. The three orthogonal gradients method was useful to demonstrate the difference in the diffusion coefficients in various diseases due to its larger total gradient strength. The clear distinction between the cytotoxic edema, which revealed slower diffusion, and the vasogenic edema, which revealed faster diffusion, was demonstrated in the experimental models using diffusion weighted image. In the clinical cases, faster diffusion was demonstrated in the brain tumor and perifocal vasogenic edema, which was in agreement with the results in the experimental models of rats. Brain tumors such as low grade astrocytoma with microcysts and perifocal vasogenic edema have very wide extracellular space.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The effect of convection on bidirectional peritoneal solute transport: predictions from a distributed model.

A distributed model of the peritoneum has been proposed as an alternative to the standard membrane model for describing peritoneal solute transport. The effect of convection on bidirectional peritoneal solute transport is studied theoretically using the distributed model. Approximate analytical and exact numerical solutions to the distributed model yield predictions similar to those when using a membrane model of peritoneal solute transport. Difficulties in interpretation of the membrane transport parameters may arise, however, when interstitial tissue, not the capillary wall, is the dominant diffusive solute transport resistance. Under such conditions the effect of convection on peritoneal solute transport is dependent on the transport direction. Moreover, predictions from the distributed model are similar to those for a membrane model containing two transport barriers in series. Thus, both the distributed model and a membrane model containing two serial transport barriers equivalently describe the effect of convection on bidirectional peritoneal solute transport.

Animals

Maximal oxygen consumption and pulmonary diffusing capacity: a direct comparison of physiologic and morphometric measurements in canids.

The purpose of this study was to check the validity of the morphometric model for estimating physiological conductances for gases, DL. We make a direct comparison between the lung's conductance for carbon monoxide, measured physiologically using the single breath method, DLCO (sb), and that measured morphometrically using the previously published model, DLCO(mm). We also make a direct comparison between the maximum rate of oxygen uptake by the lung during exercise, VO2max, and the lung's conductance for oxygen DLO2(mm). We made these measurements on four species of canids (foxes, coyotes, dogs and wolves). We find a direct proportionality between morphometric and physiologic DLCO measurements, the morphometric being consistently larger by a factor of two. We also find that both DLCO and DLO2 increase more steeply with body mass than VO2max, the difference between the allometric slopes being the same as we had found previously in a wide range of mammalian species ranging from 2 g to 700 kg, although the slopes themselves were different. We conclude that the discordant scaling of DLO2 and VO2max with respect to body mass is not an artifact of the model for calculating DLO2 from morphometric data.

Animals

Recovering membrane interaction kinetics of single molecules from 3D tracking data.

Interactions between cytosolic biomolecules and the bacterial inner membrane are fundamental to many cellular processes, yet directly measuring their binding kinetics in living cells remains challenging. Conventional 2D single-molecule tracking analyses can be insufficient, particularly when membrane association does not markedly alter the diffusion rate. Here, we present a method to recover membrane interaction kinetics from 3D single-molecule trajectories in rod-shaped bacteria. Using simulated 3D tracking data, we identify membrane-associated motion by quantifying how well short trajectory segments follow the circular curvature of the cell membrane. The resulting measure is further analyzed using a hidden Markov modeling framework, enabling robust discrimination between cytosolic and membrane-bound states and capturing the dynamics of state transitions without requiring diffusion-rate changes or direct colocalization with membrane markers. This work establishes a general framework for extracting membrane interaction kinetics from 3D single-molecule tracking data in live bacteria and highlights the value of realistic microscopy simulations for quantitative interpretation and systematic bias assessment.

Kinetics

Determinants of time-dependent membrane conductance. The nonrole of classical ion-membrane molecule interactions.

We have examined the steady-state and time-dependent electrical properties of a model membrane system. The model assumes that the directed velocity and energy of ions moving through the membrane are determined by the applied electric field, ionic diffusion forces, and central elastic collisions between ions and membrane molecules. A simple analysis of the steady-state electrical properties of the model yields results identical with ones obtained previously using a more complex analysis procedure. The time-dependent conductance changes of the model in response to a step change in electric field strength when there is solution symmetry display three qualitative patterns dependent on the nature of the ion-membrane molecule interaction. One of the patterns of conductance change is quite similar to that observed in the sodium conductance system of a number of excitable tissues: an initial conductance rise to a maximum (activation) followed by a decay to a final steady-state value (inactivation). However, the correspondence between the time-dependent model behavior and known experimental behavior of excitable systems is only qualitative. We conclude that the classical ion-membrane molecule interactions we consider are not involved in determining time-dependent conductance processes in the excitable systems for which comparison is possible.

Biological Transport

Paracrine control of photomembrane removal.

Photomembrane turnover in vertebrate photoreceptors is regulated by light. Rod outer segments (ROS) shed membrane filled tips at light onset, during the coexistence of two light modulated processes: a dark priming factor and a light induction event. Transduction of these two signals is not direct but appears to involve the neural retina and diffusible paracrine molecules. I propose a model wherein three paracrines control this ROS tip shedding. Melatonin, a lipid soluble dark priming molecule, is synthesized in the dark by all photoreceptor cells, diffusing freely and separating the ROS disk membranes. A second paracrine, dopamine is released from the inner retina whenever light is absorbed by the 502 nm-cones, inhibiting melatonin synthesis. Third, a proposed trophic paracrine, "rostrophin", is released in the dark from internal horizontal cells, and stabilizes the photomembrane. Shedding occurs as rostrophin decreases in the presence melatonin; briefly at light onset or continuously in red or dim white light.

Animals

Determination of glucose diffusion coefficients in biofilms with micro-electrodes.

A glucose micro-electrode was developed for direct measurements inside biofilms, and applied for the determination of effective diffusion coefficients in a model system of agar beads containing immobilized yeast cells. Two methods were used, one based on concentration gradients present at the liquid/solid interface of an active biofilm under steady-state conditions, the other based on the rate of glucose redistribution in an inactivated biofilm under transient-state conditions. Additional measurements with pH and oxygen micro-electrodes were performed and thus allowed for in-situ correction of the glucose electrode signal. From the micro-electrode measurements in the model system it was concluded that the glucose micro-sensor is a useful tool with which to obtain effective diffusion coefficients in biofilms.

Agar

Lithium stimulation of granulopoiesis in diffusion chambers--a model of a humoral, indirect stimulation of stem cell proliferation.

Lithium has been recognized as a stimulator of granulopoiesis both in vivo and in vitro. The mechanism by which lithium provokes this stimulation is unclear, with previous data focusing on such divergent causes as direct effects on progenitor cells v elevations in granulocyte macrophage colony-stimulating activity (GM-CSA) production. In the present study, we used a model system of granulopoiesis in diffusion chambers to study this stimulation of granulopoiesis. Lithium pretreatment of mice followed by a rest period to allow for excretion of the lithium (confirmed by serum assays) revealed a stimulation of progenitor cell growth within the diffusion chambers. No changes in the serum and chamber fluid GM-CSA levels were discernible between the control host mice and the lithium-pretreated mice. These data indicate that lithium stimulates granulopoiesis by an indirect mechanism that does not appear to involve GM-CSA.

Animals

Numerical determination of intestinal membrane diffusing constants by a gradient method.

Optimisation problems arising in the identification of kinetic parameters of intestinal membranes are here considered. The dynamic behaviour of the membrane is described by means of a linear compartmental model. Using optimisation techniques of a gradient type, the intestinal kinetic parameters are identified, minimising a quadratic criterion between experimental data of D-histidine transport and model prediction. Numerical results are reported and their physiological implications discussed. The quantitative assessment of the asymmetry of diffusion constants with respect to diffusion direction seems to be an important result of this work.

Biological Transport

[Asymptotic solution of the model of the erythrocyte shape as an autowave process].

An asymptotic solution was plotted for a model of erythrocyte forms assuming that the biomembrane is anisotropic and of "small" thickness. This leads to small non-linearity and low diffusion, therefore the solution is unrelaxational. The model was investigated qualitatively assuming that the liquid current directed inside the spheric membrane induces its "distension", while that directed outside-its "crumpling". In the spherical system of coordinates the lines of solution level at theta = const are circumferences, while at phi-const-trochoids (Pascal coil, for example). Trochoids rotation areas show stomacyte and discocyte forms. Several hypotheses based on the analysis performed are advanced.

Erythrocyte Membrane

Stromal regulation of epithelial function.

Stromal influences upon epithelia are part of a continuum of cellular interactions that begins at fertilization and extends into adulthood. In parenchymal organs, the most thoroughly characterized interactions have been those that occur during development between mesenchyme, embryonic stroma, and epithelium. Mesenchyme is essential for epithelial proliferation, morphogenesis, and differentiation. Hormones affect stromal-epithelial interactions, and in some cases, steroid hormones may produce their effects on the epithelium indirectly, acting via the mesenchyme. In many adult organs the epithelia continually proliferate and differentiate and consequently may be considered developing systems within the mature organism. This is especially true in organs with a rapidly renewing epithelium, such as the intestine, and in organs that have cycles of functional activity, such as those of the female reproductive system. The mechanisms by which stroma affects epithelial structure and function are not well understood. Current models of how signaling may be accomplished include transmission via diffusible substances, via the extracellular matrix (ECM), and via direct cell-cell contact. Growth factors and organ-specific paracrine factors are candidates for stromal cues that affect the epithelium in some systems. Components of the ECM appear to play a role in permissive interactions and may affect epithelial function by changing cell shape or by binding ECM to the cell surface integrin receptors. Signaling via direct stromal-epithelial contact may be accomplished via interactions between complimentary cell surface adhesion molecules. The importance of stromal-epithelial interactions is reemphasized by several models of carcinogenesis that suggest that perturbations in these interactions may be involved in tumor progression.

Adult