The epithelial polarity program: machineries involved and their hijacking by cancer.

The Epithelial Polarity Program (EPP) adapts and integrates three ancient cellular machineries to construct an epithelial cell. The polarized trafficking machinery adapts the cytoskeleton and ancestral secretory and endocytic machineries to the task of sorting and delivering different plasma membrane (PM) proteins to apical and basolateral surface domains. The domain-identity machinery builds a tight junctional fence (TJ) between apical and basolateral PM domains and adapts ancient polarity proteins and polarity lipids on the cytoplasmic side of the PM, which have evolved to perform a diversity of polarity tasks across cells and species, to provide 'identity' to each epithelial PM domain. The 3D organization machinery utilizes adhesion molecules as positional sensors of other epithelial cells and the basement membrane and small GTPases as integrators of positional information with the activities of the domain-identity and polarized trafficking machineries. Cancer is a disease mainly of epithelial cells (90% of human cancers are carcinomas that derive from epithelial cells) that hijacks the EPP machineries, resulting in loss of epithelial polarity, which often correlates in extent with the aggressiveness of the tumor. Here, we review how the EPP integrates its three machineries and the strategies used by cancer to hijack them.

Computerized data processing in the clinical laboratory.

In order to satisfy the increasing demand for clinical chemical investigations, automatization is necessary. Computerized data processing facilitates administrative work. There are well-known fully automatized computerized systems, but they are too expensive. This paper presents our experiences with a 'hybrid' system, in which manual laboratory work is combined with computerized production of the daily list of laboratory work. The manpower needed had been decreased to one quarter, the work time from 126 minutes to 97 minutes, and the occurrence of errors from 0.72% to 0.21%. The system can be developed to produce laboratory reports, and for the continuous monitoring of data. In the case of pathological values the reports can be supplied with a warning signal and the system is suitable for the registration of laboratory statistics.

The role of blood coagulability and axial streaming of erythrocytes in determining F cells-value and TPR.

Experiments were performed in anaesthetized and splenectomized dogs to influence the intravascular distribution of erythrocytes and plasma within the vascular bed. Blood volume was determined by double-isotope labelling of red cells and plasma. A significant decrease of F cells-value was found after posthaemorrhagic haemodilution and after haemodilution induced by homologous plasma. The administration of epsilon-amino caproic acid and bovine thrombin was followed by a significant increase of F cells-value. An interdependence of coagulability and F cells-value is suggested. The increase of haematocrit was followed by an increase of TPR, which, however, was only half of the value that would have been anticipated on the basis of the increase of viscosity when measured in normal-bore viscometers. This points to the possibility that blood flowing in the resistance vessels undergoes a certain spontaneous separation of cells and plasma and its haematocrit will be lower than in the large vessels. Cell separation in different organs having different haematocrit values and blood volumes probably affects total body haematocrit and F cells-value.

The ratio of body haematocrit to venous haematocrit in open heart surgery and estimation of the blood volume in the large and small vessels.

Double tracer blood volume technique revealed in open heart surgery patients a wide variability of Fcells-value in about 11 per cent of cases investigated, from the "normal" 0.91 value. The possible calculational error of blood volume measurements by single-isotopic--haematocrit methods in the normal or subnormal LVH-ranges point to the superiority of plasma volume determinations in the calculation of the total blood volume. The calculation of the volume of the blood-component actually not-labelled during single-isotopic--haematocrit procedures can be so highly inaccurate because of the hidden deviation of Fcells-value, that such misleading arithmetics has no real value and therefore should be omitted. Estimation of the large vessel and small vessel volumes and haematocrits in patients showed a rough 70 per cent---30 per cent distribution of the circulating blood volume between large and small vessels and an LVH tosmall vessel haematocrit ratio of 2:1 to 2:1.5. This offers a possibility to divide the circulating blood volume into a haemodynamically active (large vessel area) and a metabolically active (small vessel area) part, which can have important diagnostic and prognostic implications.

Haemodynamic and respiratory changes accompanying haemorrhagic shock in thoracotomized dogs.

Haemorrhagic shock was induced after thoracotomy by bleeding into a reservoir and the reduction of systemic blood pressure to 40 mm Hg. After two hours the blood was retransfused. The haemodynamic and respiratory changes due to the haemorrhage and retransfusion were noted during the two hour shock period and one hour after transfusion. The results were as follows: 1. Pulmonary mean and systemic mean pressure during haemorrhage and retransfusion do not change in parallel; 2. there is a rapid rise in pulmonary arterial [PA] and pulmonary capillary [PC] pressure during retransfusion; 3. cardiac output and its pulmonary fraction decrease during shock and cardiac output failed to normalise on retransfusion of the lost blood; 4. pulmonary vascular resistance, pulmonary total resistance increase significantly at the end of the shock period and after retransfusion; 5. shunt volume, alveolo-arterial O2 difference, the difference in arterio-alveolar co2 tension and dead space ventilation increase; while 6. o2 consumption and CO2 production decrease; 7. arterial blood gas values alone do not indicate those serious metabolic; circulatory and respiratory changes which develop in the lung during shock; 8. effective pulmonary compliance and the plasma oncotic pressure decrease, indicating interstitial oedema; 9. the primary mechanism responsible for the disorder during shock is not entirely clear but beside a number of other factors, the importance of the hypoperfusion of the bronchial circulation is stressed; 10. the conclusions permit a certain insight into the pathogenesis and therapeutic possibilities of the adult respiratory distress syndrome.