Bittar - Böcker

As a result of the key advances made more than 30 years ago, specifically the ability to isolate islets of Langerhans from the pancreas, the ability to measure insulin accurately by immunoasay, and the development of microchemical techniques for studying cells and their components, many research volumes, symposium reports, and original papers have been produced. This explosion of interest has probably had at least three stimuli:

1. the inherent scientific interest in understanding secretion of the pancreatic �-cell2. the �-cells relevance to a very common disease3. the availability of funding from specific sources related to diabetes research, for instance, Juvenile Diabetes Foundation International and the British Diabetic Association.

As a result of all this activity, detailed scientific literature including research reviews are readily available.

Surprisingly enough, there are relatively few attempts to summarize this great bulk of knowledge in a way that is accessible to the newcomer to this field and this book is intended to bridge this gap.

Volume 1 of the series Fundamentals of Medical Cell Biology is devoted to evolutionary biology. This is presented in two parts: in the first, the structure and dynamics of RNA, DNA, and protein are dealt with. The second part is concerned with the origins and cellular basis of life.

Volume 1 of the series Fundamentals of Medical Cell Biology is devoted to evolutionary biology. This is presented in two parts: in the first, the structure and dynamics of RNA, DNA, and protein are dealt with. The second part is concerned with the origins and cellular basis of life.

The purpose of this volume is to provide a synopsis of present knowledge of the structure, organisation, and function of cellular organelles with an emphasis on the examination of important but unsolved problems, and the directions in which molecular and cell biology are moving. Though designed primarily to meet the needs of the first-year medical student, particularly in schools where the traditional curriculum has been partly or wholly replaced by a multi-disciplinary core curriculum, the mass of information made available here should prove useful to students of biochemistry, physiology, biology, bioengineering, dentistry, and nursing.It is not yet possible to give a complete account of the relations between the organelles of two compartments and of the mechanisms by which some degree of order is maintained in the cell as a whole. However, a new breed of scientists, known as molecular cell biologists, have already contributed in some measure to our understanding of several biological phenomena notably interorganelle communication. Take, for example, intracellular membrane transport: it can now be expressed in terms of the sorting, targeting, and transport of protein from the endoplasmic reticulum to another compartment. This volume contains the first ten chapters on the subject of organelles. The remaining four are in Volume 3, to which sections on organelle disorders and the extracellular matrix have been added.

This volume is in two parts. The first contains the remaining chapters on cellular organelles and several chapters relating to organelle disorders. An account of mitochondriopathis is given in the chapter on the mitochondrion rather than in a separate one. The subject matter of this part of the volume shows quite clearly that the interdisciplinary approach to the study of organelles has shed considerable light on the nature of the mechanisms underlying the etiology and pathobiology of many of these disorders. As an example, mutations in the genes encoding integral membrane proteins are found to lead to disturbances in peroxisome assembly. It is also interesting and significant that mistargeting of protein is now thought to be another cause. It will be revealing to see whether mistargeting is the result of mutations in the genes encoding chaperones.The second part of the volume is concerned with the extracellular matrix. It sets out to show that a vast body of new knowledge of the extracellular matrix is available to us. Take for example the integrin family of cell adhesion receptors. It turns out that integrins play a key role not only in adhesion but also in coupling signals to the nucleus via the cytoskeleton. As for fibronectins, they seem to link the matrix with the cytoskeleton by interacting with integrins.Collagen molecules are dealt with in the last two chapters. The boundaries of collagen in disease are defined by drawing a clear line of demarcation between systemic connective tissue disorders (e.g., scleroderma), better known as autoimmune diseases, and the heritable, and the heritable diseases such as osteogenesis imperfect and the Marfan syndrome. This classification takes into account a second group of acquired disorders of collagen forming tissues in which regional fibrosis is the hallmark. Liver cirrhosis and pulmonary fibrosis are prime examples.The decision to place Volumes 2 and 3 before those dealing with cell chemistry was not easily made. It was based on the view that most students will have had an undergraduate course in biochemistry of cell biology or both courses, and that they could go to Volumes 4-7 in which the subject of cell chemistry is covered, and then return to Volumes 2 and 3.

This is the first of a 4-volume module that is an introduction to the study of cell chemistry and physiology. It is not intended to be encyclopedic in nature but rather a general survey of the subject with an emphasis on those topics that are central to an understanding of cell biology and those that are certain to become of increasing importance in the teaching of modern medicine.We have followed what appeared to as to be the logical divisions of the subject beginning with proteins. Allewell and her colleagues stress the point that proteins fold spontaneously to form complex three-dimensional structures and that some of them unfold with the help of proteins called chaperones. Michaelis-Menten kinetics are shown by Nelsestuen to describe the behaviour of enzymes in the test tube. The formalism is particularly useful in the search for agents of therapeutic value, as exemplified by methotrexate. Uptake by mammalian cells of substrates and their metabolic conversions are discussed by van der Vusse and Reneman. However, both Welch and Savageau expound the view that the cell is not simply a bagful of enzymes. The biologist is urged by Savageau to abandon Michaelis-Menten formalism and apply the Power Law. The biologist is also told that the approach to arriving at a theory of metabolic control would have to be one of successive approximations requiring the use of the computer. Information gained from comparative biochemistry is shown by Storey and Brooks to have shed new light on mechanisms of metabolic rate depression and freeze tolerance, and to be applicable to organ transplantation technology. We are reminded that enzyme adaptation is partly the result of the presence of a hydrating shell of vicinal water that stabilises conformation of the enzyme. Vicinal water, according to Drost-Hausen and Singleton, lies adjacent to most solids and protein interfaces. The kinks or breaks observed in the slope of the Arrhenius plot are attributed to structural changes in vicinal water. Regulation of cell volume is shown by Hempling to involve regulation of cell water. It could be that the osmo-receptor or volume detection system is a protein that links the cytoskeleton to specific K and C1 channels. Additionally, it is interesting that aquaporins, which are water channel-forming membrane proteins, are now known to exist in both renal and extra-renal tissues. One of the renal porins is affected by vasopressin. We then pass on to protein synthesis (Rattan) and other important topics including protein glycosylation (Hounsell), methylation (Clarke), ADP-ribosylation (Pearson) and prenylation (Gelb). Among the four types of lipids attached to membrane proteins are the prenyl groups. Ford and Gross in their chapter on lipobiology drive home the point that there is an accumulation of acyl carnitine and lysophospholipids during myocardial infarction.

This volume illustrates the extent to which the traditional distinction between biochemical and physiological processes is being obliterated by molecular biology. It can hardly be doubted that the revolution in cell and molecular biology is leading to core knowledge that provides an outline of the integrative and reductionist approach. We view this as the beginning of a new era, that of the integration of learning.As in the preceding volumes, the choice of topics has been deliberate not only because of the need to keep the volume within reasonable bounds but also because of the need to avoid information over-load. Several relevant topics are dealt with in other modules; for example, the role of G proteins in transmembrane signalling is covered in the Membranes and Cell Signalling module (i.e., Volume 7). Omissions are of course inevitable but they are minor. A case in point is the subject of phosphatases, the treatment of which does not take into account calcineurin. One of the key functions of this Ca2+ -activated protein phosphatase that is also regulated by calmodulin is to desphosphorylate voltage-dependent Ca2+ channels. The mere recognition of such omissions before or after consulting textbooks and journals should be a spur to a more complete discussion by the student of the subject in a small group teaching setting.

This volume is intended to complete the Cell Chemistry and physiology module. It is about how the traditional boundaries of cell chemistry and physiology are being erased by molecular biology. We do not think it necessary to elaborate on this theme, particularly since the body of core knowledge found in this volume brings us a stage closer to answering the question, "what makes cell biology into a new discipline?"The first part of the volume deals with the chemistry of actin and myosin and is followed by chapters on cell motility, ATP synthesis in muscle, and contraction in smooth and skeletal muscle. Here the reader is immediately made aware of the contributions molecular biology is making to our understanding of the molecular mechanisms underlying muscle contraction. It is perhaps enough to point out that Huxley's concept of the cross-bridge cycle and generation of force can now be explained in molecular terms. Topics such as muscle fatigue and muscle disorders, as well as malignant hyperthermia are bound to arouse active learning in the student and set the stage for problem-based learning.Most medical students look askance at thermobiology. We think this is a mistake; hence, we have included a section dealing with this subject. This brings us to the chapter on the heat shock response, which at the very outset makes clear that many stressors besides heat are known to result in heat shock gene expression. Many of the heat shock proteins occur in unstressed cells and some of them behave as chaperones. These proteins also reach high levels in a wide range of diseases including neurodegenerative disorders. Whether certain diseases are the result of mutations in the heat shock genes is not yet known. As will be appreciated, much of the work done in this field involved the use of cultured cells. Animal cells in culture are the subject of the last chapter.