Living organisms exhibit specific responses when confronted with sudden changes in their environmental conditions. The ability of the cells to acclimate to their new environment is the integral driving force for adaptive modification of the cells. Such adaptation involves a number of cellular and biochemical alteration including metabolic homeostasis and reprogramming of gene expression. Changes in metabolic pathways are generally short-lived and reversible, while the consequences of gene expression are a long-term process and may lead to permanent alternation in the pattern of adaptive responses.
The heart possesses remarkable ability to adapt itself against any stressful situation by increasing resistance to the adverse consequences. Stress composes the foundation of many degenerative heart diseases including atherosclerosis, spasm, thrombosis, cardiomyopathy, and congestive heart failure. Based on the concept that excessive stress may play a crucial role in the pathogenesis of ischemic heart disease, attempts were made to design methods for preventing of myocardial injury. Creation of stress reactions by repeated ischemia and reperfusion or subjecting the hearts to heat or oxidative stress enables them to meet the future stress challenge. Repeated stress exposures adapt the heart to withstand more severe stress reactions probably by upregulating the cellular defense and direct accumulation of intracellular mediators, which presumably constitute the material basis of increased adaptation to stress. Thus, the powerful cardioprotective effect of adaptation is likely to originate at the cellular and molecular levels that compose fundamental processes in the prophylaxis of such diseases.
Volume six of the Advances in Organ Biology series contains state-of-the-art reviews on myocardial preservation and cellular adaptation from the leading authorities in this subject.

This fourth volume in the series on biochemistry looks at foundations in modern biochemistry. Topics covered include: the genetic solution; the genetic basis of development; DNA repair; evolution in an RNA world; nitrogen fixation; solute channels; viruses; biochemistry in retrospect and propspect.

Retinoids have received considerable attention in recent years and due cognizance has been given to their versatility as biological response modifiers, as evidenced by the virtually explosive growth of literature in this field in the past few years. This volume has been designed to give a current state-of-the-art picture of retinoids. The perceived potential of retinoids in the treatment of certain disease stated has initiated attempts at identifying and synthesizing new retinoid derivatives with definable and selective effects on aberrant biological phenomena. Appropriately, therefore, we begin with the chemistry of retinoids and their derivatives together with discussions of their biological activity. Major advances have been made in understanding the mechanisms by which retinoids modulate physiological and phenotypic traits of cells. The transduction of retinoid signaling by the mediation of nuclear receptors of the steroid/thyroid receptor superfamily has now been studied extensively and the cloning and defining the characteristics of these receptors has been a focus of discussion in this volume. Retinoids also markedly modulate the transduction of extracellular signals such as those imparted by growth factors and hormones, and thus actively influence and control cellular proliferative patterns. Retinoids can alter epidermal growth factor receptor expression (Kawaguchi et al., 1994), responsiveness to thyroid hormone (Esfandiari et al., 1994; Pallet et al., 1994), inhibit the proliferative responses of hematopoietic progenitor cells to granulocyte colony stimulating factor (Smeland et al., 1994), and modulate secretion on interleukins by leukaemic cells (Balitrand et al., 1994), among other things. This has obvious implications for pharmacological manipulation of deregulated growth (Dickens and Colletta, 1993; Mulshine et al., 1993). Apoptosis is another component in the regulation of growth control. Apoptotic cell death is influenced by several agents and retinoids may function by interfering with apoptotic pathways of regulation of growth control and quite legitimately, therefore, the importance of this aspect of retinoid function has been duly recognized here.

Lipobiology is a rapidly evolving interdisciplinary field which incorporates critical aspects of lipid and lipoprotein chemistry into the disciplines of cell biology and physiology. This series focuses on salient aspects of the role of lipids in metabolic regulation and cellular activation.

The Editors invited selected authors who had participated in or observed the explosive development of biochemistry and molecular biology particularly in the second half of this century to record their personal recollections of the times and circumstances in which they did their work. The authors were given a completely free rein with respect to both content and style and the editors have made no attempt to impose any sort of uniformity in the chapters. Each reflects the flavour of the personality of the author.

The contributors to this volume encompass a wide variety of experiences in many different countries and in very different fields of biochemistry. Some have worked close to the laboratory bench throughout their scientific life and are continuing to do so. Others have been closely engaged in organisational matters, both nationally and internationally. All mention incidents in their own career or have observed those in others that will be of interest to future historians who will record and assess the period in which our contributors lived and worked. It was an extremely exciting time for life sciences.

The contributors to this text, who are all biochemists who worked during the 1950s and 60s, describe what appears to them to be the conceptually significant developments in biochemistry since the mid 1950s and how these were achieved. Their aim is to make their subjects intelligible to other scientists not expert in their field.

This volume deals with some of the multiple systems that growth factors and cytokines affect. The role of growth factors and cytokines on foetal development, in the immune and haemopoietic systems as well as in the skeletal and reproductive systems are covered. Various cancers are examined in a number of the chapters. This is the third and concluding volume of the treatise on growth factors and cytokines in health and disease.

It should not come as too much of a surprise that biological membranes are considerably more complex than lipid bilayers. This has been made quite clear by the fluid-mosaic model which considers the cell membrane as a two-dimensional solution of a mosaic of integral membrane proteins and glycoproteins firmly embedded in a fluid lipid bilayer matrix. Such a model has several virtues, chief among which is that it allows membrane components to diffuse in the plane of the membrane and orient asymmetrically across the membrane. The model is also remarkable since it provokes the right sort of questions. Two such examples are: Does membrane fluidity influence enzyme activity? Does cholesterol regulate fluidity? However, it does not go far enough. As it turns out, there is now another version of this model, the so-called post-fluid mosaic model which incorporates two concepts, namely the existence in the membrane of discrete domains in which specific lipid-lipid, lipid-protein and protein-protein interactions occur and ordered regions that are in motion but remain separate from less ordered regions. We must admit that both are intriguing problems and of importance in guiding our thinking as to what the next model might be.
We have chosen not to include the subject of membrane transport in the present volume. This obviously represents a break with convention. However, the intention is to have the topic covered subsequent volumes relating to organ systems. It would be right to regard this as an attempt to strengthen the integrated approach to the teaching of medicine.

Volume 6 of Biomembranes covers transmembrane receptors and channels. A particularly important role for the membrane is that of passing messages between a cell and its environment. Part I of this volume covers receptors for hormones and growth factors. Here, as in so many other areas of cell biology, the application of the methods of molecular biology have led to the recognition of a number of families of receptors. Typically, such receptors contain an extracellular ligand binding domain, a transmembrane domain, and an intracellular catalytic domain whose activation, as a result of ligand binding, leads to generation of second messengers within the cell and stimulation of a range of cytosolic enzymes. An alternative signaling strategy, exploited in particular in the nervous system, is to use ion channels to allow controlled movement of monovalent (Na+, K+) or divalent (Ca2+) cations in or out of the cell, resulting in changes in membrane potential or alterations in the intracellular concentration of Ca2+. Part II of this volume is concerned with these ion channels and with other, often simpler, ion channel systems whose study can throw light on channel mechanism.

This is the fourth volume in the series, aimed at those wishing to stay abreast of developments in the mechanisms and synthetic applications of 1,3-dipolar cycloaddition reactions.

The aim of this text is to provide reviews and monographs on topics involving molecular similarity, ranging from the fundamental physical properties underlying molecular behaviour to applications in industrially important fields such as pharmaceutical drug design and molecular engineering. The editors hope that this series will encourage new ideas and approaches, help to systematize the rapidly accumulating new chemical information, and make chemistry better understood and better applied.

Volume 4 of Biomembranes covers endocytosis, exocytosis and related processes. A major role of the plasma membrane is as a permeability barrier, keeping the inside of the cell inside and the outside, outside. Mechanisms must then exist to allow movement of material between the cell and its environment. One mechanism for export from the cell is by exocytosis, a process in which the membranes of secretory vesicles fuse with the plasma membrane releasing the contents of the vesicle into the extracellular medium. The process has been studied in particular depth for the release of neurotransmitters at the synapse. Import into the cell is possible by the process of receptor-mediated endocytosis in which selected plasma membrane proteins are internalizes; when these proteins are receptors for macromolecules, the result is uptake of the macromolecule. Transferring, the low-density lipoprotein, and asialoglycoproteins are all taken up into cells in this way. Phagocytosis, the ingestion of cells and cell fragments by neutrophils and macrophages, also involves receptors - on the phagocytic membrane - of which the best studied are those for the Fc domain of IgG, for the third component of complement, and for the mannose/fructose carbohydrates. Protection of a host against infection can also be achieved by damaging the integrity of the plasma membrane of the invading organism. This is the strategy evolved by the cytotoxic T lymphocytes, which produce a pore-forming toxin, perforin. Volume 4 of Biomembranes explores the structures and mechanisms involved in these biologically and medically important processes.

Volume 5 of Biomembranes covers an important group of membrane proteins, the ATPases. The P-type ATPases couple the hydrolysis of ATP to the movement of ions across a membrane and are characterized by the formation of a phosphoyrlated intermediate. Included are the plasma membrane and muscle sarcoplasmic reticulum Ca2+ -ATPases, the (Na+ -K+) -ATPase, the gastric (H+ -K+) -ATPase, the plasma membrane H+ -ATPase of fungi and plants, the Mg2+ - transport ATPase, the Salmonella typhimurium, and the K+ -ATPase of Escherichia coli, KdpB. The other important classes of ATPase in eukaryotic systems are the vacuolar H+ -ATPases and the F0F1 ATP synthase, and, in bacteria, the anion-translocating ATPases, responsible for resistance to arsenicals and antimonials, and the (Na+ -Mg2+) -ATPase of Acholeplasma. Finally, eukaryotic systems contain a variety of ectonucleotidases important, for example, in hydrolysis of extracellular ATP released as a cotransmitter from cholinergic and adrenergic nerve terminals. Volume 5 of Biomembranes explores structure-function relationships for these mebrane-bound ATPases.

This series presents reviews covering all aspects of haemodynamics and haemorheology. Topics covered include the complexities of microcirculation, the rheology of blood and blood vessels, and the mechanics of blood flow in arteries and veins. The contributions aim to reflect the advances being made in experimental techniques and instrumentation for laboratory and clinical measurements and in numerical and mathematical modelling. Emphasis is placed on the scientific and engineering principles involved, but particular attention is also given to the clinical significance of this area of research. Topics covered by this volume include viscoelastic properties of blood and blood analogues; blood flow through narrow tubes; and numerical modelling of blood flow.

Lipobiology is an interdisciplinary field which incorporates critical aspects of lipid and lipoprotein chemistry into the disciplines of cell biology and physiology. During the last decade, advances in our understanding of the structure and function of lipids, biological membranes and lipid-derived second messengers have underscored the importance of lipids in the regulation of cellular function. This series focuses on salient aspects of the role of lipids in metabolic regulation and cellular activation, with emphasis on emerging concepts and technologies. One goal of this series is to formulate cohesive criteria upon which a foundation for the evaluation of recent work can be based and future directions of research identified.

This volume covers such quantum leaps in the field of biochemistry as the coding properties of DNA and the central dogma, manipulating DNA, extranuclear DNA, protein synthesis and the ribosome, and cell cycles.

The quantity of information available about membrane proteins is now too large for any one person to be familiar with anything but a very small part of the primary literature. A series of volumes concentrating on molecular aspects of biological membranes therefore seems timely. The hope is that, when complete, these volumes will provide a convenient introduction to the study of a wide range of membrane functions.
Application of the techniques of molecular biology has provided the sequences of a very large number of membrane proteins, and has led to the discovery of superfamilies of membrane proteins of related structure. The classic example of the superfamily is the seven helix receptor superfamily, all related in structure to bacteriorhodpsin, and named after the seven trans-membrane a-helices identified in bacteriorhodpsin. This volume explores the structures and functions of this super family.

This series provides a variety of different discussions on topics within the field of growth factors and cytokines in health and disease.

Volume 3 of Biomembranes covers receptors of cell adhesion and cellular recognition. Proteins in the plasma membrane of cells are heavily involved in processes of cell adhesion, but such proteins were not actually isolated and characterized until the mid-1970s. Since then, application of the methods of molecular biology has led to the recognition of four major classes of cell adhesion molecule (CAMs), the immunoglobulin super family, the cadherins, the integrins, and the selecting. A convenient system in which to study the importance of cell adhesion is in blood platelets where aggregation eventually leads to thrombus formation in a process involving a range of surface glycoproteins. Interaction with the extracellular matrix is exemplified by CD44, the receptor for hyaluronan, and a complex carbohydrate that is a major component of the extracellular matrix surrounding migrating and proliferating cells. Membrane-associated mucins have a variety of effects on cell adhesion. The super family of immunoglobulin related proteins also include the T cell receptors and the major histocompatibility complex (MHC), which, together with the receptors for immunoglobulins (the Fc receptors), are of fundamental importance in the processes of immunity. Volume 3 of Biomembranes explores the structures and functions of the molecules involved in these important functions of the cell.

This volume deals with aspects of the cytoskeleton in different cell types and also describe examples of changes in the cytoskeleton which occur during various pathological states. These studies bring the exciting area of cytoskeleton research into the domain of medical science.

This is the third volume in a series on membrane protein transfer. Membrane protein transport underlies the topological disposition of many proteins within cells and it is this disposition that allows for the co-ordination of the central cellular processes, such as metabolism.

The second volume in a series which aims to focus on advances in computational biology. This volume discusses such topics as: statistical analysis of protein sequences; progress in large-scale sequence analysis; and the architecture of loops in proteins.

The Genetical Theory of Natural Selection by R.A. Fisher (1930) dictated that sexual dimorphisms may depend upon a single medelian factor. This could be true for some species but his suggestion could not take off the ground as gender in Drosophila is determined by the number of X chromosomes. Technical advances in molecular biology have revived the initial thinking of Fisher and dictate that TDF or SRY genes in humans or Tdy in mice are sex determining genes. The fortuitous findings of XX males and XY female, which are generally termed sex reversal phenomenon, are quite bewildering traits that have caused much amazement concerning the pairing mechanism(s) of the pseudoautosomal regions of human X and Y chromosomes at meiosis. These findings have opened new avenues to explore further the genetic basis of sex determination at the single gene level.
The aim of the fourth volume, titled Genetics of Sex Determination is to reflect on the latest advances and future investigative directions, encompassing 10 chapters. Commissioned several distinguished scientists, all pre-eminent authorities in each field to shed their thoughts concisely but epitomise their chapters with an extended bibliography. Obviously, during the past 60 years, the metoric advances are voluminous and to cover every account of genes, chromosomes, and sex in a single volume format would be a herculean task. Therefore, a few specific topics are chosen, which may be of great interest to scientists and clinicians. The seasoned scientists who love to inquire about the role of genes in sex determination should find the original work of these notable contributors very enlightening. This volume is intended for advanced students who want to keep abreast as well as for those who indulge in the search for genes of sex determination.

This is the second volume in a series on membrane protein transfer. Membrane protein transport underlies the topological disposition of many proteins within cells and it is this disposition that allows for the co-ordination of the central cellular processes, such as metabolism.

It is now clear from a wide range of research that cytoplasm is not merely a buffered solution of proteins and enzymes but contains a series of complex filamentous structures. The cytoskeleton is the collective term given to these filaments. There is a considerable amount of data available on the protein composition of the major filament systems (microfilaments, microtubules, and intermediate filaments) but we are still comparatively ignorant about the role of the cytoskeleton in cell physiology. However such major cytoplasmic components (actin and tubulin, the monomeric constituents of microfilaments and microtubules, are major cell proteins) must have important roles to play in cell function, and investigations into the functional role of the cytoskeleton currently represent a major area of cell biological research.
In recent years rapid advances in molecular biology have begun to influence research on the cytoskeleton. This trend is sure to continue and the techniques of molecular biology and genetics are set to make major contributions to our understanding of the cytoskeleton, as illustrated in this volume by several reviews; the use of transfection techniques by Ben-Ze'ev, the power of Drosophila genetics is described by Fyrberg and the major advances made in the inesin field using molecular approaches as described by Cyr et al. The chapters by Fyrberg and Cyr et al. also illustrate two other areas where major advances in our understanding of the cytoskeleton is occuring; the great array of different motor proteins involved in intracellular movements and the study of the cytoskeleton in developmental biology.
Overall, Volume 12 in this series illuminates our increasing knowledge of the important roles of the cytoskeleton in cell function, particularly how it is central to metabolic organization, intracellular transport, interactions with matrix, and nerve function. Our knowledge of the cytoskeleton is now reaching a stage where it is clear that abnormalities in the organization of the cytoskeleton can lead to important clinical manifestations of disease; an example of how such research is now impinging on medical science is presented in the final chapter by Lane on keratin diseases.