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Biomedical subjects

W Wierzbicki

Publications and source records attributed to W Wierzbicki.

6 recordsLinked to original sources

Trimmed radiosurgical fields.

Radiosurgery aims to deliver a high radiation dose to a small target volume while sparing surrounding healthy tissues. However, since the target volume is often large and irregularly-shaped, a significant amount of healthy tissue is irradiated. To improve conformity of the dose volume to the target volume, we propose to optimize the field shape by trimming the field described by the radiosurgery cone with the accelerator jaws for a given arc. We have measured output factors (OF), tissue-maximum ratios (TMR), off-axis ratios (OAR) and penumbrae for 40, 32.5 and 24 mm cone fields trimmed by the lower (i.e., X jaws) and /or upper (i.e., Y jaws) collimator jaws. The smallest field was 8 mm large, and length was limited by the cone size. The average penumbra due to the cone field is 2.8 mm, and 4.1 and 6.1 mm for those due to the X and Y jaws, respectively. Moreover, the penumbrae due to the X and Y jaws are independent of jaw position within the radiosurgical field. Because of the large penumbra involved with the Y jaws, radiosurgical fields should be trimmed by the X1 and/or X2 jaws only. The measured OF's have been fitted with a hyperbolic function. All of the fitted OF's fall within +/- 0.5% of the measured OF's. The TMR values obtained with trimmed fields do not change much, except for the smallest fields (up to 10% at a depth of 20 cm). Therefore, using trimmed radiosurgical fields requires straightforward dosimetric changes and provides a level of beam shaping for large cone fields (> 20 mm in diameter) without introducing additional hardware.

Equipment Design↗

An analytical expression for electron beam central axis depth doses.

An analytical expression based on four fitting parameters is proposed for a mathematical description of electron beam central axis depth dose distributions. The expression approximates well the measured electron beam data in the field size range from 4 x 4 cm2 to 25 x 25 cm2 and in the energy range from 6 to 20 MeV in all four regions of the electron depth dose curve: build-up, dose maximum, dose fall-off, and bremsstrahlung contamination.

Humans↗

The amino-terminal segment of the catalytic subunit of kidney Na,K-ATPase regulates the potassium deocclusion pathway of the reaction cycle.

Tryptic cleavage of the catalytic subunit of kidney Na,K-ATPase in the E1 conformation effects a change in kinetic behavior apparent at low ATP concentration. Thus, at < or = 10 microM ATP, K+ inhibits Na(+)-dependent ATPase activity of the undigested enzyme but activates activity of the digested enzyme. With time of trypsinolysis, a transient increase followed by a decrease in activity is observed at low [ATP], whereas at high [ATP] (1 mM), activity is progressively reduced. At low [ATP], the trypsin-treated/control activity ratio was > or = 3-fold higher with K+ compared to the ratio observed with the K+ congener Li+. Also, the relative Na/K exchange activity (22Na+ influx into K(+)-loaded inside-out vesicles from erythrocytes) with either 0.01 mM ATP or 1 mM CTP compared to 1 mM ATP was greater for the trypsin-treated than for the control enzyme. The kinetic change is correlated with the initial rapid cleavage of the N-terminal tryptic fragment (< or = 30 residues) from the catalytic subunit. It is concluded that this segment regulates the K+ deocclusion pathway of the reaction; removal of this fragment produces a modified active species having an increased rate of K+ deocclusion.

Animals↗

Membrane transport models with fast and slow reactions: general analytical solution for a single relaxation.

Membrane transport models are usually expressed on the basis of chemical kinetics. The states of a transporter are related by rate constants, and the time-dependent changes of these states are given by linear differential equations of first order. To calculate the time-dependent transport equation, it is necessary to solve a system of differential equations which does not have a general analytical solution if there are more than five states. Since transport measurements in a complex system rarely provide all the time constants because some of them are too rapid, it is more appropriate to obtain approximate analytical solutions, assuming that there are fast and slow reaction steps. The states of the fast steps are related by equilibrium constants, thus permitting the elimination of their differential equations and leaving only those for the slow steps. With a system having only two slow steps, a single differential equation is obtained and the state equations have a single relaxation. Initial conditions for the slow reactions are determined after the perturbation which redistribute the states related by fast reactions. Current and zero-trans uptake equations are calculated. Curve fitting programs can be used to implement the general procedure and obtain the model parameters.

Animals↗

Presteady-state kinetics and carrier-mediated transport: a theoretical analysis.

Kinetic studies of cotransport mechanisms have so far been limited to the conventional steady-state approach which does not allow in general to resolve either isomerization or rate-limiting steps and to determine the values of the individual rate constants for the elementary reactions involved along a given transport pathway. Such questions can only be answered using presteady-state or relaxation experiments which, for technical reasons, have not yet been introduced into the field of cotransport kinetics. However, since two recent reports seem compatible with the observation of such transient kinetics, it would appear that theoretical studies are needed to evaluate the validity of such claims and to critically evaluate the expectations from a presteady-state approach. We thus report such a study which was performed on a simple four-state mechanism of carrier-mediated transport. The time-dependent equation for zero-trans substrate uptake was thus derived and then extended to models with p intermediary steps. It is concluded that (p-1) exponential terms will describe the approach to the steady state but that such equations have low analytical value since the parameters of the flux equation cannot be expressed in terms of the individual rate constants of the elementary reactions for models with p greater than 5. We thus propose realistic simplifications based on the time-scale separation hypothesis which allows replacement of the rate constants of the rapid steps by their equilibrium constants, thereby reducing the complexity of the kinetic system. Assuming that only one relaxation can be observed, this treatment generates approximate models for which analytical expressions can easily be derived and simulated through computer modeling. When performed on the four-state mechanism of carrier-mediated transport, the simulations demonstrate the validity of the approximate solutions derived according to this hypothesis. Moreover, our approach clearly shows that presteady-state kinetics, should they become applicable to (co)transport kinetics, could be invaluable in determining more precise transport mechanisms.

Animals↗

Locomotion of granulocytes on an inclined plane.

The paper presents a quantitative study of the trajectories of rat granulocytes (PMNs) migrating on a glass surface inclined at various angles, i.e. under the action of gravitational force component parallel to the plane. The action of the force of the order of 5 X 10(-13) N (component parallel to the plane inclined at 80 degrees) accompanied by the decrease of a gravitational component perpendicular to the surface does not disrupt the adhesion contact of migrating PMNs with the serum coated glass surface. Under the action of the external force parallel to the surface, the PMNs exhibit a tendency to migrate in the direction of the force vector and the angles between elementary segments (steps) of cell trajectories are smaller in comparison with migration on a horizontal plane (0 degrees inclination). It has been found that the mean velocity of motion of PMNs locomoting on a steep slope (70 degrees and 80 degrees) is greater in comparison with the migration velocity on a horizontal surface. The increase of velocity concerns not only cells migrating in the downward direction, but also those which move upwards. Possible mechanisms of the influence of external force on direction and rate of migration of granulocytes are discussed, namely modification of adhesion force, stimulation of cell motile activity, individual variability of cell adhesive and migration properties, shortening of transient locomotory adhesions.

Animals↗