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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.

Molecular and Cell Endocrinology

There is a need in small group teaching for a readable module that provides a balanced treatment of the four main areas of medical microbiology-bacteriology, mycology, virology and parasistology. It need not be encyclopedic in scope nor didactic, but it should emphasise principles and concepts. Any existing gaps in this type of presentation are, of course, left for the student to fill.Some subject material has been excluded. An example is a chapter on laboratory procedures including PCR for rapid bacterial and viral diagnosis. The discussion of bacterial sexually transmitted diseases does not cover goncoccal infections. This is not a serious matter because the tutor can assign the topic to the students. Moreover, we have reluctantly omitted a separate chapter on anaerobic bacteria. The subject of nosocomial pathogens is touched upon but not in sufficient detail (e.g., control). These bacteria (e.g., S. aureus, E. coli and pseudomonas) are found in hospitals and are resistant to disinfectants and antibiotics. A new but serious problem is the emergence of resistance to antiviral agents.Without question, molecular biology owes more to the study of viruses than bacteria. The fact remains, however, that effective therapy against most viral diseases is not yet available. Perhaps one of the most dramatic examples of this situation is the fight against the AIDS virus and the search for a vaccine. The public health challenge of AIDS remains formidable in spite of the recent encouraging results obtained with protease inhibitor therapy. At the moment at least six receptors for HIV are known to be present in human cells. One of them is the CCR5 receptor in the absence of which cells fail to get infected with the virus. Drugs that can interrupt CCR5 binding sites on the virus envelope are being vigorously sought. Thus, Volume 9B gives a large place to HIV disease.The last group of chapters highlight several features of microbiology which are also of clinical importance and heuristic value. The chapter on fever of unknown origin provides fertile soil for problem based learning.

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.

We have now reached the mid-point of our editorial task of putting together the compendium, Principles of Medical Biology, which is supposed to be composed of twenty-five modules. The present single-volume module on reproductive endocrinology and biology is in more than one respect a continuation of Module 10 (in two volumes) dealing with molecular and cellular endocrinology. In addition, it intersects, as it should, with various parts of obstetrics and gynaecology, both of which are abetted by technology. One has only to recall that the practical benefits of ultrasound in perinatal medicine and in vitro fertilisation are the outcome of the technological revolution in biomedicine. Whether we are approaching a new era in reproductive biology following the invention of animal cloning is still hard to tell. For some people, it remains an article of faith that cloning of the human being is highly probable. For others, asexual reproduction is anathema. It should surely be obvious to us all that somatic cell nuclear transfer technology (SCNTT) is going to be at its strongest in dealing with husbandry. Whether this and several social forces will alter our modern outlook, there can be little doubt.As in diverse clinical and basic research, so in obstetrics, animals are used as a model. The data thus obtained is extrapolated, if valid, to the mother and foetus. The success of this approach is exemplified in studies carried out on sheep as a model. On the whole, it is also quite apparent that progress in the field of reproductive biology is to a large extent ascribable to the discovery in other disciplines of new hormones, as well as the introduction of new tools and recent improvements in laboratory methods including measurement of hormones.

Molecular and Cellular Pharmacology

The purpose of this module is to provide a survey of the rapidly expanding field of developmental biology and to introduce it to the student in a unifying way. In medical schools where courses in biochemistry, physiology, and pharmacology are already considerably intersecting, there is not surprisingly a rising demand in modern medical education for books emphasizing the interdisciplinary approach. In recent years, developmental biology has become a very vibrant and exciting field. The adoption of the interdisciplinary approach in this field has yielded enormous information about how DNA is able to produce a living organism from a fertilized egg. The discovery of'master'genes in Drosophila that control spatial organization and share a segment of DNA, the so-called homeobox, and the discovery in C. elegans of genes controlling the timing of branching off of cell lineages are today recognized as milestones in molecular developmental biology.Because of space limitations and because of the information explosion, we have continued to pursue the policy of selecting broad topics but not in every case. This time, for example, though guided by the principle that a close connection exists between genes, adhesion, and morphogenesis, we opted to include certain topics such as cadherin - an adhesion molecule - rather than have the whole subject of adhesion dealth with in a single chapter. Substrate-adhering molecules (e.g., fibronectnin) are touched upon in Chapter 5. In a similar manner, only one type of junction is discussed at length. Chapters 8, 9, and 10 border on the extraordinary, for they are together absorbingly interesting. The last chapter makes things more pragmatic. The attention of the reader is drawn to the fact that several previous volumes of the compendium impinge on the present one. Chapters 25 and 26 in Volume 7B, in particular, have much to say on the subjects of extracellular matrix adhesion and intercellular communication.

As this volume demonstrates, immunobiology is a young science which is undergoing explosive growth. Judged by results, it is already an elaborate discipline which cuts across every other area in biomedical research and even has its own vocabolary (e.g., the'veto'effect). Rather than inculcate the habit of superficial learning by having the student go through a maze of details, we have sought to gather together sixteen essays that range from T-cells to psyhoneuroimmunology. This is keeping with the growing understanding that the student is expected to read and think far more for herself/himself.Next to nothing is known about innate immunity. However, recent evidence suggests that collectins might bridge the gap between innate immunity and specific clonal immune responses. Collectins are soluble effector proteins that include serum mannose-binding protein, and lung surfactants A and D. They are considered to be ante-antibodies.