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Biomedical subjects

J Rashbass

Publications and source records attributed to J Rashbass.

9 recordsLinked to original sources

The biological toolbox: a computer program for simulating basic biological and pathological processes.

The program described here has been written to enable pathologists and biologists with almost no computer experience to design complex models of cell interactions. The program although simulating in only two dimensions allows the user to define the individual rules governing cell behaviour using a language called Cell Description Language, then simulates the multiple interactions between the cells to produce a dynamic visual interpretation representing tissue growth and differentiation. The program has been developed using the World Wide Web, thereby giving access to anyone with an Internet connection. The Web technology allows others to use our powerful computers to perform the complex calculations that are necessary and effectively eliminates the problems of modifying and compiling the program to run on more than one hardware platform. The changes that take place during the simulation are presented as a video using the MPEG video format; they may then be viewed on many different types of computers. The toolbox provides a novel approach to computer-based biological simulations and an excellent resource for teaching.

Biology

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Computer Communication Networks

The use of a computer model to simulate epithelial pathologies.

The complexity of the interactions of the many rules governing cell behaviour and the changes that lead to the pathological features seen in disease is such that linking cause and effect can be very difficult. However, the use of computers to model normal biological and pathological processes provides a powerful technique for studying the effects of the interactions of a variety of biological rules. Such an approach is strengthened by using a graphical display that simulates the organization of cells in a tissue. Skin, and specifically the epidermis, is characterized by a regular morphology and the ability to regenerate itself throughout adult life and there are considerable biological data available on the normal and pathological process that affect this organ. A model of normal skin has been developed which shows a structure similar to normal epidermis and is capable of healing itself if damaged. This paper describes the effects on the overall structure of introducing mutations to individual rules in the model. Changes that alter cell proliferation or differentiation are introduced and the effects that these produce are compared with epidermal pathologies. Even a simple model is capable of producing insights into the types of events that may occur in a variety of dermatopathological conditions.

Basement Membrane

A networked computer program for managing a national external quality assurance scheme in cytopathology.

We described a computer program to manage a national external quality assurance (EQA) scheme in cytopathology which uses the international computer network, the Internet, to collect data directly from participants, thereby reducing errors of transcription and administrative costs. Feedback to screeners and pathologists is provided as high quality images of the diagnostic areas on the slide which are only available once all users at a centre have entered their answers. This allows comparison with the original material while it is still available at this site. Users are encouraged to register differences of opinion by labelling areas on images of the slides on the computer. The program performs the statistical analysis of the data for each centre and each slide.

Computer Communication Networks

A computer graphic simulation of squamous epithelium.

An epithelium maintains its integrity through the organized growth and orderly differentiation of a transient cell population derived from stem cells. This organization is dependent upon both physical mechanisms such as cell adhesion and attraction and the relationship between differentiation and cell division. The interactions between these processes are complex and difficult to conceptualize from a purely mathematical approach. We have therefore set out to develop a graphic model of an epithelium controlled by rules that can be modified. We have chosen to model epidermis, the most superficial part of skin, with cells differentiating from a stem cell population and being lost from the surface of the model. The model is novel not only in the rules that govern cell behaviour, but also because it does not require a predefined lattice to assign the position of cells. Each cell assumes a position depending upon the balance of adhesive and repulsive forces that it experiences. Chemical factors which affect the differentiation of individual cell types are assumed to be produced both by cells within the model and externally from the underlying connective tissue. These "chemical factors" diffuse through the model with a concentration that declines as an inverse square with distance from the source. The rules allow the model to grow from a single stem cell to reach a steady state. At steady state the pattern and clonal structure is strikingly similar to that seen in a range of normal epithelia. Furthermore, if part of the model is removed it is capable of regenerating itself without additional rules. The model allows the visualization of the effects of introducing new rules and modifying the interaction between chosen rules. This study demonstrates that a set of simple rules can be used to make a dynamic flexible model resembling skin.

Animals

The DNA-binding protein E12 co-operates with XMyoD in the activation of muscle-specific gene expression in Xenopus embryos.

Two alternatively spliced products of the human E2A gene, E12 and E47, encode helix-loop-helix DNA-binding proteins. Here we describe the isolation of two Xenopus cDNAs; one, XE12, is structurally similar to human E12 and the other contains a sequence similar to E47. Transcripts of both cDNAs are present at all the stages of Xenopus development tested and in all regions of the embryo. The DNA binding properties of in vitro translated XE12 are indistinguishable from those of human E12. We have shown previously that an embryonic muscle DNA-binding activity, EMF1, that binds to a promoter sequence required for the expression of the cardiac actin gene, contains the Xenopus myogenic factor XMyoD. Here we show that it also contains protein that interacts with an anti-E12 antiserum, suggesting that XE12 and XMyoD proteins, or very similar ones, are present in EMF1. We have addressed the functional role of XE12 in muscle gene transcription in Xenopus embryos by injecting in vitro synthesized RNA into the two cell embryo. Overexpression of XE12 and XMyoD augments by greater than 10-fold the ectopic activation of the endogenous cardiac actin gene that can be produced by XMyoD alone. Our DNA binding results strongly suggest that this effect is mediated through a direct interaction of the XE12-XMyoD complex with specific sites in the cardiac actin promoter. We suggest that XE12 is functionally important in muscle gene activation in embryonic development.

Amino Acid Sequence