186 BioEssays Vol. 5, No. 4

Fibrosis: ’Friend and Foe‘ Fibrosis. Edited by D. EVERED and J. WHELAN. Symposium on Fibrosis held at the Ciba Foundation, London, October, 1984. Pitman, 1985. Pp. 256. €27.95. By Gillian Murphy To those of us who look on with envy as the experts assemble at the Ciba Foundation to discuss yet another aspect of biomedical science, the emer- gence of the published proceedings is always something of a relief to our frustrations. The Symposium on Fibro- sis¶ held at the Ciba Foundation in 1984, is no exception. A group of 14 distinguished reviewers and other expert discussants attempted to identify a unifying mechanism for the diverse disease conditions that lead to the accumulation of fibrous tissue, as well as reviewing possible models and thera- pies for these diseases. Under the chairmanship of Allen Bailey, they assessed our understanding of the basic regulatory mechanisms for the synthe- sis, assembly and degradation of the major structural element of connective tissue, collagen. The formation of con- nective tissue is part of the normal healing process after injury but in some cases an abnormal and excessive depo- sition of matrix can occur. Fibrotic dis- orders can affect nearly all organs and tissues and include such major health problems as rheumatoid arthritis, atherosclerosis and pulmonary and liver fibrosis. The chairman’s strategy, to analyse the problem at a basic scientific level, has resulted in a useful treatise on the biology of connective tissue, and collagen in particular, as well as an overview of current thinking about fibrotic diseases.

The first half of the book considers the biochemistry of collagen and its biosyn- thesis. To define a triggering mechanism for collagen synthesis, we need to start at the gene level. Benoit de Crombrugghe et al. described current knowledge of the collagen genes’ structure, their pro- moters and other regulatory elements controlling expression, and consider strategies for the therapeutic control of synthesis. The extensive co-translational and post-translational modifications to the collagen molecule also present suitable targets for pharmacological intervention (Kivirikko and Majamaa). Current ideas on potential antifibrotic agents acting at all levels of collagen turnover are extensively discussed by the participants. Trelstad and Birke

describe their elegant model of extra- cellular compartmentation of the fibro- blast for the assembly of collagen fibres during matrix deposition and rearrange- ment, and extend this to a mechanism of collagen degradation. The precise structure of collagen fibres from X-ray diffraction analysis suggests that the fibres in fibrotic lesions are similar to those in normal connective tissue (Miller et a / ) . However, the ability of the fibrils to stabilize by cross-linking in mature fibrotic lesions is of paramount importance, since they become less susceptible to enzyme attack and hence turnover (Bailey and Light). Knowledge of the regulatory mechanisms of colla- gen degradation is still at an early stage, but a failure to degrade the excesses of collagen synthesized in fibrosis contri- butes to the disease and may present a potential control point in the future design of therapeutic approaches (Krane).

Central to the metabolism of connec- tive tissue is the fibroblast, a cell specialized for establishing, maintaining and repairing the matrix structure. Fibroblast behaviour is largely deter- mined by complex interactions with other cell types, and this is considered in the second half of the book. The nature of the intercellular messengers probably varies according to the tissue and its physiology or pathology, hence the contributors concentrate on their ob- servations within a particular model or disease condition. Hunt et al. describe the cooperation between macrophages, fibroblasts and endothelial cells in models of wound healing. Their point that this field is ‘ drowning in acronyms symbolizing uncharacterized small pro- teins which facilitate cell division or behaviour’ is well made, however! Some specific examples of chemo- attractants and cytokines are discussed in further chapters, and it seems evi- dent that these play a role in the initiation and progression of fibrotic disease. However, more detailed analy- sis of the individual effectors and their mode of action will be needed before any semblance of order is seen in the plethora of observations that have been made. Of particular importance are the immune factors regulating fibrosis; the contribution of lymphocytes to the control of fibroblast growth and matrix production is analyzed by Wahl. Inhibi- tors produced by both monocytes and lymphocytes could be important in regulating inflammation-dependent fi- brosis, and it may be the absence of

such cells in mature lesions that permits collagen deposition to become progres- sive and irreversible.

The book will be of interest to both connective-tissue biologists and clini- cians as an overview of current research on collagen, particularly in relation to the physiology and pathology of fibrosis. This is evidently a multi-factorial disease and the discussion of the roles of genetic, immunological and biochemical factors and their inter-relationships is particularly good, thanks to the multi- disciplinary nature of the forum. Such an honest appraisal of the usefulness of various approaches, or their deficiencies, is of importance to those looking for an insight into the problems of fib1 research.

GILLIAN M U R P H Y is at the Strangeways Research Laboratory, Worts Causeway, Cambridge CBl 9RN, UK.

The Cell Cycle: A Superior Overview The Biology of Cell Reproduction. By RENATO BASERGA. Harvard University Press, 1985. Pp. 251. E19.95. By J. M. Mitchison This is an excellent book. It is a worthy successor to Prescott’s Reproduction of Eurkaryotic Cells published 10 years ago, and it iscertainly the best up-to-date book on the cell cycle. It is almost entirely concerned with mammalian cells, with an occasional discussion of yeast, but this is a field of major interest and of rapid advance. There is no question that this book should be studied by research workers in this area and by senior-level undergraduates. It also gives a superior overview of the mammalian cell field which will be of great value to those working with prokaryotes and lower eukaryotes.

The major part of the book covers the cell cycles of mammalian cells with accounts of macromolecular events, control points and cell-cycle genes. But the coverage is wider than the cell cycle in the strict sense since there are chapters concerned with tissue growth, oncogenes, growth factors and the control of proliferation.

There is a lot of information including a number of very useful tables about particular points. But this is neither the papers in-book’sclothing of conference