Solving pathophysiological problems.

The aim of this paper was to analyze particular aspects of problem solving in pathophysiology. It is related to various kinds of knowledge presentation (textbook-type descriptions and computer programs) that are important for reasoning.

An analysis of the meaning of some concepts related to health.

From the logical point of view health is a certain condition (state) of the human organism, i.e. a set of the organism's attributes. The components of an abstract (general) notion of health, i.e. its features, are classes of phenomena which may be ascribed to a given individual. The concrete notion of health (condition of health) of a given individual embraces particular realisations of the features, i.e. values or properties of the organism. The health attributes are one-argument relations as well as two- or multi-argument ones. The health features and properties are either external (subjectively and/or intersubjectively observable) or internal (characterizing the internal parts of the organism). The distinction of normal (positive) and abnormal (negative, pathological) external and internal health properties is based mainly on systemic, statistic and subjective criteria. According to the everyday usage, the sets of external negative properties are illnesses, while the sets of internal negative ones that provoke (actually or potentially) and illness correspond to diseases or pathological entities.

The method of moments as applied to the study of granulocytes' shape and movement.

The paper presents an approach to the quantitative analysis of the shape and motion of migrating granulocytes based on the method of moments. A computer image analysis system and a specially designed program were used. The following features of cells and cell locomotion have been calculated: the cell centre of gravity and its coordinates, the cell displacement, the main cell axis, the coefficient describing cell elongation and the parameters of cell orientation. In order to evaluate the above approach under various conditions, comparative experiments were performed using the media of different viscosity and various positions of the plane on which the granulocytes were migrating. The cell shape and locomotion parameters estimated in various series of experiments indicate that the method may be generally useful and is able to detect not only major features of cell shape and movement, but also their relatively slight variations. The experiments performed in basic (typical) conditions revealed that the main axis of the majority of cells (about 60%) does not deviate from the global direction of migration by an angle greater than 30 degrees; about 10% of cells move with the main axis perpendicular to this direction. The broader frontal part of granulocytes is directed forward with regard to the global movement direction in 58% of cells, whereas 28% of the cells move with the tail pointing forward. The results of joint analysis of the cell shape and motion have confirmed statistically some well known features of migrating granulocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Simple logical structures of medical reasoning and action.

The aim of this study is to delineate the fields of research on medical problem solving and action in which the use of logical methods may be fruitful and to describe the topics related to these fields in a way which would make easier further formal analysis. Four types of reasoning, namely, direct inference, verification of hypotheses, proving and explanation, are distinguished; simple examples of their application in the diagnostic and therapeutic inference-making are presented, and a complex, systemic character of reasoning in actual situations is described. The remarks concerning logical questions connected with the time factor, uncertainty and health values indicate the main sources of difficult problems which appear in a formal analysis. Medical action is represented as a sequence of consecutive, parallel and ramified diagnostic and therapeutic stages; the role of the plan of action and the importance of the cooperation between the doctor and the patient are stressed.

Adhesive and motile properties of Lewis lung carcinoma LL2 lines.

The cell substrate adhesion of the Lewis lung carcinoma in vitro maintained sublines (LL2 basic line, WGA-resistant LL2-8, and Aleuria aurantia-resistant LL2-AAA) has been studied by a hydrodynamic method using various shearing forces generated by the medium flow. The force of adhesion of the LL2 cells is about 10(-12) N to 10(-11) N with statistically significant differences between various sublines: it is the highest for LL2-AAA cells, intermediate for LL2 cells and the smallest for LL2-8 cells. In another series of experiments the distribution of the number of single cells and multicellular aggregates in the suspensions of LL2 cells together with the effect of gravitational sedimentation were examined. When the LL2 cells are incubated in 37 degrees C they display active motile behaviour which consists in forming cell-surface extensions of various shapes and duration (from a few seconds to several minutes and more). The displacement of the whole cells (locomotion) has not been observed. The results of the study on adhesion and motility of LL2 cells are discussed from the point of view of their metastatic properties, cell-membrane structure and mechanisms of malignant invasion.

Adhesion and locomotion of granulocytes under flow conditions.

The aim of this study was to compare the strength of the surface adhesion of migrating human granulocytes and the main parameters of their locomotion under the influence of various external forces. The strength of adhesion of granulocytes moving in a quiescent medium was studied by detaching them gravitationally from the plane surface situated above them. In these conditions the force of adhesion is of the same order of magnitude as the gravitational force operating upon the cells. The locomotion characteristics of granulocytes migrating on a surface below them are similar to those observed during their movement on a surface above. When the granulocytes migrate with the medium flowing past them, they are not detached from the surface even by relatively great shearing forces (10 and 100 times greater in comparison with the gravitational force) and the locomotion parameters are only slightly modified. The results show that granulocytes are able to migrate in a similar manner when they are subjected to various external forces.

Model structure of a fragment of biological knowledge (cell motility).

The aim of the study is to contribute to a better understanding of some aspects of the structure of biological knowledge and to make clearer to what extent the methods of reasoning may be useful in this field when only qualitative information is available. A fragment of biological knowledge (theory of cell motility) is analysed from the logicomethodological point of view as a coherent system and the possibility of its formal representation is investigated. The analysis is based on distinguishing the main objects and their features (attributes) of which a given piece of knowledge is composed and on the values which these features may display. The features are interconnected by relations (in which various number of arguments appear) and these relations constitute the main (general, higher level) laws of a given fragment of knowledge (theory). Values of attributes are also mutually connected and these relations correspond to the detailed (lower level) laws. A computer system (in which Prolog language was used) enables to perform inference operations of progressive as well as regressive type. The main categories of reasoning procedures are described and illustrated by examples, namely a) search for conclusions which may be confronted with the actual knowledge in order to verify the system as a whole, b) formation of working hypotheses in the process of their empirical verification and explanation of facts and laws. The problem of development and modification of the system is also discussed.

Poiseuille flow method for measuring cell-to-cell adhesion.

A theoretical description of the cell aggregation process in the Poisseuille flow is presented, the capture efficiency being used as the measure of cell adhesiveness. The value of this coefficient is determined both for nonspecific and specific (i.e., mediated by molecules) cell-to-cell interactions. Regarding the cell adhesion described by the DLVO theory, it is possible to determine the conditions under which cell adhesion is maximal. The dependence of capture efficiency on parameters such as shear rate, size of cell, surface potential of cell, the Hamaker constant of substances constituting the cell membrane, and composition of the medium is analyzed. In the case of specific cell adhesion during flow, the change of suspension concentration is related to the number of free and occupied receptor sites, the diffusion constant of the receptors in the cell membrane, the force of a single bond, and the conditions of flow. It is possible to determine the diffusion constant from cell aggregation measurement when the force of a single bond and the number of free and occupied receptor sites are known.

Specific cell-to-cell adhesion under flow conditions.

An experimental method of measuring intercellular adhesion based on cell interactions in Poiseuille flow is presented. Hydrodynamic conditions of suspension flow, concentration of the suspension, and the size of cells allows determination of the capture efficiency, which is a measure of cell adhesiveness. The measurements of cell aggregation were performed with thymus cells and lectin from Ricinus communis. On the ground of theoretical description of the process of cell aggregation, it was possible to estimate the diffusion constant of the receptors in the cell membrane, which is equal to 5.6 X 10(-11) cm2/s. This value is in good agreement with the results of direct measurements of the diffusion constant of the lectin receptor. In the case of formalin-treated cells, the diffusion constant of the lectin receptors is equal to 6.8 X 10(-12) cm2/s. The total number of the receptor sites on the thymus cell surface for lectin R. communis and the affinity constant were also estimated.

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.

Adhesion and locomotion of L5222 cells on endothelium, collagen and glass.

Examination was made of the adhesive interaction of L5222 leukemia cells with endothelial cells, collagen and glass and of cell locomotion on endothelium and collagen. Leukaemia cells interacted with the substrate under stationary conditions. The fraction of cells adherent to the substrate was defined next, using the given shearing force caused by the medium flowing through the measuring channel. The relative number of adherent cells, A (related to the number of cells after sedimentation), remaining on the given surface despite the detaching action of shearing force, F, was determined. The range of F values applied was 0.1 to 30 (x 10(-13)) N. It was found that the relation A(F) is a decreasing function for all the substrates examined and takes on values in the relation 1:2:6 for cells adherent to collagen, glass and endothelium, respectively. The critical value of F, at which values of A are maintained at a constant level close to zero, was 0.5, 1 and 3 (x 10(12)) N, respectively, for cells adherent to these substrates. The function A(F) for L5222 cells adherent to endothelial cells and to glass can be described well by the formula: A = a/square root F (where a = constant greater than 0). Studies of L5222 cell locomotion on an endothelial cell layer and on collagen revealed that the pattern of locomotion, variations in locomotion velocity and the mean values of cell displacement (5.8 and 5.0 micrometers, respectively) are similar for both substrates.

Surface interactions of leukemia and red cells passively moving in a quiescent fluid.

Adhesion to glass and silicone-coated surface of leukemia cells (L1210 and L5222) and their motion on an inclined plane have been investigated. The cells in quiescent fluid are subjected to the action of gravitational force; its component parallel to the surface ranges from 4.0 x 10(-14) N to 4.5 x 10(-13) N. The prolonged action of the gravitational force at 45 degrees (3.3 x 10(-13) N) causes the separation from the substratum of numerous cells which have adhered on a horizontal plane. When the cells passively move on the slope they are frequently arrested by adhesion which is partly short-lived. The analysis of the leukemia cell velocity reveals good agreement with the theory describing the motion of a sphere in quiescent fluid. The translation movement of nucleated cells on an inclined plane is not, however, accompanied by rotation. On the other hand, the cells flowing in mid-stream rotate with an angular velocity predicted by the theory.

Contact of migrating L5222 leukemia cells with the substrate as studied under the action of gravitational force.

The interaction of actively migrating L5222 cells with the serum-coated glass surface was studied under the influence of an external force. In order to generate such force, the plane on which the cells were migrating, was inclined at different angles. The analysis of the L5222 cell migration pattern reveals that the modification of the cell movement direction relative to the surface appears when the plane is inclined at 1 degree. The increase of the slope to 2 degrees makes this effect more evident. When the slope is equal to 3 degrees the active motion of L5222 cells seems to disappear. The component of the gravitational force parallel to the plane on which the cells migrate ranges from 6.3 X 10(-15) N to 1.9 X 10(-14) N for the slopes from 1 degree to 3 degrees, respectively. The results of the study indicate that the force of interaction of migrating L5222 cells with the substrate is very small in comparison with the force of adhesion (not accompanied by locomotion) and seems to be comparable to that which operates in the near-substrate region of non-locomotive cells (e. g. L1210). Thus, the cell-substrate contact related to active movement and the non-locomotory adhesion of L5222 cells are probably different phenomena. As only L5222 cells were studied in this work, the above conclusions should be restricted to this cell type only.