Search

A genetic engineering approach is described for directed immobilization of IgG-binding receptors to a thiolcontaining matrix using a single cysteine residue. The cysteine residue is introduced into the C-terminal part of receptors based on staphylococcal protein A. Receptors containing one, two or five IgG-binding domains were produced in Escherichia coli and subsequently immobilized on thiopropyl-Sepharose. A high amount. 5 µmol/ml gel (45 mg/ml), of recombinant receptor could be rapidly immobilized to the solid support and both the gel and the immobilized receptor could be regenerated by reduction and oxidation reactions. The gel was used for affinity purification of human IgG and analysis of IgG-binding capacity at different amounts of immobilized recombinant protein show the same maximal IgG-binding capacity (20-25 mg/ml) for all three immobilized receptors. However, at low substitution grade of receptors, the immobilized receptor molecules were shown to bind one (Z-Cys) and two (ZZ-Cys) IgG molecules, respectively. These results demonstrate that the immobilized protein molecules are in a functionally active form and that a two-domain receptor can bind two molecules of IgG without steric hindrance. Interestingly, the five-domain receptor (ZV-Cys), with a structure similar to native protein A, can only bind approximately two IgG molecules, despite the five-domain structure of the molecule. [ABSTRACT FROM AUTHOR]

Biological cells, healthy or malignant, perform in most respects similar activities:(a) They proliferate by growing and maturing and, after reaching a certain level of maturation, they divide into daughter cells.(b) They differentiate by changing irreversibly to new types of cells.(c) They compete by participating in ecological struggles with other cells that share the same ecological niche. Through the principle of com petitive exclusion, slower-dividing cells may be eradicated from a mixture of cells.This paper presents a mathematical model of the above processes and describes a computer simulation which includes the effects of chemotherapy or radiation therapy on a system consisting of healthy and malig nant cells. The simulation develops qualitatively and quantitively the kinetic properties during treat ment of the mixture of the two types of cells in tissues and shows how the favorable protocols for treatment can be found. Such knowledge can, among other things, be used to devise good strategies for the treatment of cancer by radiation or chemotherapy and to increase the efficiency of research in their use.The example described is a simplified one in which only two types of cells are considered, but the simu lation model can be applied to much more complex and realistic situations. [ABSTRACT FROM PUBLISHER]

A queuing system with exponentially distributed service times and constant interarrival times is studied for the case with one service station. The characteristics of the queue are determined both in its transient part and in its steady part. The cost of the system is defined as a linear sum of the cost of keeping customers waiting for service and the cost of having the service station idle. The statistical distribution of this cost is derived and it is also shown how its mean may be minimized by proper choices of the constant interarrival time and the initial numbers of customers in the queue. [ABSTRACT FROM AUTHOR]