S. Papa – författare

Understanding the function and diseases of the nervous system with a view to treating problems effectively has long been a major concern of neurobiologists and clinicians. The recent rapid development of molecular biology investigatory techniques has facilitated major advances in this field and the aim of this book is to provide an up-to-date review of recent findings on neurological disorders with particular emphasis on how an understanding of molecular processes can contribute to an understanding of the aetiology and mechanisms of disease causation. An examination of normal function provides the basis for a discussion of dysfunction including the affects of pharmacological agents and toxic insults. The broad-ranging coverage includes: cell membranes and ionmotive systems; molecular biology of receptors; ion channels; metabolic aspects; magnetic resonance, spectroscopic and positron emission tomographic studies of neurological disorders; regulation of cerebral microcirculation; brain ischaemia and its treatment; and neurotoxicity and xenobiotic agents.Deriving from an international meeting held in Sasano, Bari, Italy in September 1989, which included a workshop on mitochondrial encephalomyopthies, and written by an international team of experts, this topical book provides a good combination of molecular and clinical information and a strong indication of the areas in which further research is needed. It should be a vital reference source for biochemists, molecular biologists, neurobiologists, pharmacologists and neurologists. This book should be of interest to research workers in biochemistry, molecular biology, neurobiology, pharmacology and clinicians in neurology and psychiatry.

The topics contained in this book represent timely and currently exciting areas of research focused on mitochondria. It forms a comprehensive and up-to-date record of present knowledge at the molecular level of many important mitochondrial processes. Major achievements as well as new openings in the field have been stressed in many of the contributions to the book. Thus, it represents a valuable source and reference book, comprising the most recent results in this area. The topics treated should attract the attention of scientists from various fields, who are interested in bioenergetics, molecular biology and pathology of mitochondria.

This volume is based on the proceedings of an International Symposium on "Cytochrome Systems: Molecular Biology and Bioenergetics" that was held at Selva di Fasano near Bari, Italy, between April 7 and 11,1987. It contains papers covering the subjects discussed at the Symposium, contributed both by participants of the meeting and by some invited speakers who were not able to attend. The aim of the Symposium was to bring together experts in various rese­ arch strategies currently being applied to the study of cytochrome systems, including molecular genetics, protein chemistry, enzymology of electron transfer and protonmotive activity in energy-transducing biological mem­ branes. Because of the high degree of complexity of cytochrome systems and the increasing sophistication in recent years of the different experimen­ tal approaches, there has been a growing specialization - sometimes even a tendency to "over-specialization" - among scientists working in this field. This in itself seemed to justify a meeting where representatives of various disciplines could exchange their results and discuss their conclusions. In addition, and perhaps even more importantly, it was felt that meetings of this kind provide an opportunity for a "cross-fertilization" of approaches and ideas among representatives of various fields of science. The present meeting proved to be an ample illustration of the success of such an inter­ action.

This volume is based on the proceedings of an International Symposium on "Cytochrome Systems: Molecular Biology and Bioenergetics" that was held at Selva di Fasano near Bari, Italy, between April 7 and 11,1987. It contains papers covering the subjects discussed at the Symposium, contributed both by participants of the meeting and by some invited speakers who were not able to attend. The aim of the Symposium was to bring together experts in various rese­ arch strategies currently being applied to the study of cytochrome systems, including molecular genetics, protein chemistry, enzymology of electron transfer and protonmotive activity in energy-transducing biological mem­ branes. Because of the high degree of complexity of cytochrome systems and the increasing sophistication in recent years of the different experimen­ tal approaches, there has been a growing specialization - sometimes even a tendency to "over-specialization" - among scientists working in this field. This in itself seemed to justify a meeting where representatives of various disciplines could exchange their results and discuss their conclusions. In addition, and perhaps even more importantly, it was felt that meetings of this kind provide an opportunity for a "cross-fertilization" of approaches and ideas among representatives of various fields of science. The present meeting proved to be an ample illustration of the success of such an inter­ action.

One of the most obvious and fundamental properties of living things is their ability to utilize the potential energy in their environment for their own ends. It is not surprising therefore that the mechanism of this biotransformation of energy-bioenergetics-has long exercised the minds of the leading scientists of their day-from Lavoisier's recognition that respiration is fundamentally the same as combustion, Priestley's discovery of photosynthesis, and Spallan- zani's thesis that respiration is an intracellular process. Until about 30 years ago, the field of bioenergetics was the center of biochemistry, attracting many of the great biochemists of the century, such as Warburg, Keilin, Meyerhof, Engelhardt, Krebs, Lipmann, and Calvin. After the main pathways of intermediary metabolism and electron transfer were estab- lished, however, further progress in elucidating the mechanistic details was slow.This slowdown was due to the absence of sufficient knowledge of the structure of the catalysts involved, even after the innovative proposal by Mitchell on the fundamental role of the translocation of protons across mem- branes, which revolutionized the way in which the mechanism of energy transduction was envisaged and for which he was awarded the Nobel Prize for chemistry in 1978. Competition from other fields of biochemistry in which progress was more spectacular has caused funding difficulties for those work- ing in bioenergetics.

The Expert Committee on Biomaterials and Biotechnology for the European and the North American Region was founded by the General Assembly of UNESCO at its 21st Session, in 1981. The Committee comprises a Coordinating Group and four working Groups, defined in the following scientific areas: Group I Proteins: source, structure and function. Group II Nucl~ic acids: the hereditary materials. Group III Im~une materials and mechanisms. Membranes and transport in biosystems. Group IV In fulfilment of one of the objectives of the Committee, which have been adopted by the General Assembly of UNESCO in 1981, namely the intensification of the exchange of scientific information on biomaterials and biotechnology, working Group IV organized an international workshop on Ion Interactions in Energy Transport Systems, which was convened in Athens, Greece, from 8 to 12 April, 1985. Scientific papers presented at that workshop make up the chapters presented in this volume. The present volume focusses on natural and artificial membranes that are involved in energy transduction. Several chapters are devoted to membranes and membrane components that convert and utilize light, such as the thylakoid membrane of oxygenic photosynthetic organisms (eukaryotic and prokaryotic), the chromatophore membrane of nonoxygenic photosynthetic bacteria and the purple membrane of the halophilic bacteria. Other systems examined include the mitochondrial membranes and their adenine nucleotide carrier, the plasma membrane of animal cells, and lipid bilayer vesicles, either reconstituted or not, with enzymes.

The Expert Committee on Biomaterials and Biotechnology for the European and the North American Region was founded by the General Assembly of UNESCO at its 21st Session, in 1981. The Committee comprises a Coordinating Group and four working Groups, defined in the following scientific areas: Group I Proteins: source, structure and function. Group II Nucl~ic acids: the hereditary materials. Group III Im~une materials and mechanisms. Membranes and transport in biosystems. Group IV In fulfilment of one of the objectives of the Committee, which have been adopted by the General Assembly of UNESCO in 1981, namely the intensification of the exchange of scientific information on biomaterials and biotechnology, working Group IV organized an international workshop on Ion Interactions in Energy Transport Systems, which was convened in Athens, Greece, from 8 to 12 April, 1985. Scientific papers presented at that workshop make up the chapters presented in this volume. The present volume focusses on natural and artificial membranes that are involved in energy transduction. Several chapters are devoted to membranes and membrane components that convert and utilize light, such as the thylakoid membrane of oxygenic photosynthetic organisms (eukaryotic and prokaryotic), the chromatophore membrane of nonoxygenic photosynthetic bacteria and the purple membrane of the halophilic bacteria. Other systems examined include the mitochondrial membranes and their adenine nucleotide carrier, the plasma membrane of animal cells, and lipid bilayer vesicles, either reconstituted or not, with enzymes.

Rapid progress has been made in our understanding of the molecular mechanisms of cell growth and oncogenesis during the past decade. This book comprises recent results on the regulation of cell growth in normal and neoplastic tissues by growth factors including hormones, and by the activation and inactivation of oncogenes and tumor suppressor genes, respectively. Special attention has been given to the presentation of the frequently neglected close correlation between changes in signal transduction and metabolism pathways during oncogenesis.

Rapid progress has been made in our understanding of the molecular mechanisms of cell growth and oncogenesis during the past decade. This book comprises recent results on the regulation of cell growth in normal and neoplastic tissues by growth factors including hormones, and by the activation and inactivation of oncogenes and tumor suppressor genes, respectively. Special attention has been given to the presentation of the frequently neglected close correlation between changes in signal transduction and metabolism pathways during oncogenesis.

This book consists of a series of reviews on selected topics within the rapidly and vastly expanding field of membrane biology. Its aim is to highlight the most significant and important advances that have been made in recent years in understanding the structure, dynamics, and functions of cell membranes. The progress that is being made in research in this field is due to the application of integrated experimental ap- proaches, utilizing sophisticated and novel techniques in molecular biology, cell biology, biophysics and biochemistry. Due to the advances made, many problems have been or are being solved at the molecular level. With the help of an Editorial Advisory Board consisting of Jean-Pierre Changeux (Paris), Paolo Comoglio (Torino), Rainer Jaenicke (Regens- burg), Sten Orrenius (Stockholm), Lorenzo Pinna (Padova), Konrad Sandhoff (Bonn), and Gottfried Schatz (Basel), we have selected a number of topics in areas in which progress has been particularly rapid, and have invited internationally acknowledged experts in the field to review these topics.The areas covered in this monograph are: 1) Signal transduction; 2) Membrane traffic: Proteins and lipids; 3) Bioenergetics: Energy transfer and membrane transport; 4) Cellular ion homeostasis; 5) Growth factors and adhesion molecules; 6) Structural analysis of mem- brane proteins; and 7) Membranes and disease.

Rapid progress has been made in our understanding of the molecular mechanisms of cell growth and oncogenesis during the past decade. This book comprises recent results on the regulation of cell growth in normal and neoplastic tissues by growth factors including hormones, and by the activation and inactivation of oncogenes and tumor suppressor genes, respectively. Special attention has been given to the presentation of the frequently neglected close correlation between changes in signal transduction and metabolism pathways during oncogenesis.

cytochemical techniques (ICC) which provide a useful adjunct to investigations by immunoblotting. A particular advantage of a cytochemical approach to the investiga­ tion of mitochondrial disorders is that it allows the mosaic distribution of certain of these defects to be detected, whereas the tissue homogeniza­ tion involved in conventional enzyme assays or immunoblotting precludes this. A further advantage of MEA or ICC is that only small amounts of tissue are needed, which is important since many of the affected patients are infants or small children. The main aim of this communica­ tion is to outline ways in which these techniques can be used in the diagnosis and further investigation of mitochondrial disorders. Reference will be made not only to those situations in which MEA and ICC offer advantages over standard enzyme asays and immunoblotting but also to contexts in which the reverse applies. 4. 2 MATERIALS AND METHODS Muscle biopsies for cytochemical investigation were snap-frozen using isopentane cooled to - 150°C in liquid nitrogen. Samples were stored in heat-sealed polythene packets in the vapour phase of liquid nitrogen containers. 4. 2. 1 Microphotometric enzyme assays Frozen sections 8 Jlm thick were cut using a Reichert-J ung Frigocut cryostat microtome equipped with motor-driven cutting action to maintain maximal reproducibility of section thickness. Sections were picked up on microscope slides and air-dried for 15 min at room temperature.