Molecular Medicine for Clinicians

Stevens Wendy, Nanthakumarn Chetty, Ramsay Michèle, Barry Mendelow, Pascale Willem, Tracey Wiggill, Natalie Whalley, Marco Weinberg, Sarah Walters, Ahmed Wadee, Gwynneth Stevens, Himla Soodyall, Mieneke Smit van Dixhoorn, Lesley Scott, Barry Schoub, Nerina Savage, Natela Rekhviashvili, Wolfgang Prinz, Michael Pepper, Alan Paterson, Maria Papathanasopoulos, Lillian Ouko, Andries Oelofse, Grant Napier, Marion Munster, Elizabeth Mayne, Lombard Zané, Anthony Lane, Amanda Krause, Hendrik Koornhof, Penny Keene, Nicole Holland, Tabitha Haw, Kate Hammond, Nerine Gregersen, Debbie Glencross, Lindsay Earlam, Adriano Duse, Chrisna Durandt, Nigel Crowther, Leandra Cronjé, Theresa Coetzer, Gerrit Coetzee, Arnold Christianson, Alexio Capovilla, Jacqueline Brown, Sahle Asfaha, Silke Arndt, Arbuthnot Patrick

Description

The insights following the wake of the Human Genome project are radically influencing our understanding of the molecular basis of life, health and disease. The improved accuracy and precision of clinical diagnostics is also beginning to have an impact on therapeutics in a fundamental way. This book is suitable for undergraduate medical students, as part of their basic sciences training, but is also relevant to interested under- and postgraduate science and engineering students. It serves as an introductory text for medical registrars in virtually all specialties, and is also of value to the General Practitioner wishing to keep up to date, especially in view of the growing, internet-assisted public knowledge of the field. There is a special focus on the application of molecular medicine in Africa and in developing countries elsewhere.
Foreword
Acknowledgements
Chapter 1 Introduction
Barry V Mendelow and Penny Keene
KEYNOTE ESSAY 1: Defining Who We Are: DNA in Forensics, Genealogy and
Human Origins
Himla Soodyall
SECTION 1 PRINCIPLES OF CELLULAR AND 13
MOLECULAR BIOLOGY
Chapter 2 Digital Concepts in Molecular Medicine
Barry V Mendelow
Chapter 3 The Anatomy and Physiology of the Genome
Marc S Weinberg, Natalie A Whalley and Michèle Ramsay
Chapter 4 Molecular Cell Biology
Natalie A Whalley, Sarah Walters and Kate Hammond
Chapter 5 Genetic Variation
Silke Arndt and Anthony B Lane
Chapter 6 Genes in Development
Lillian A Ouko and Michèle Ramsay
Chapter 7 Tools of Molecular Medicine
(a) Nucleic Acid Methods
Natela Rekhviashvili and Gwynneth Stevens
(b) Protein Methods
Alexio Capovilla
(c) Cellular Phenotyping and Flow Cytometry
Lesley E Scott and Debbie K Glencross
(d) Molecular Cytogenetics
Pascale Willem and Jacqueline Brown
KEYNOTE ESSAY 2: The Human Genome
Michèle Ramsay
SECTION 2 MOLECULAR PATHOLOGY
Chapter 8 Genomes and the Environment:
An Overview of Molecular Pathology
Barry V Mendelow
Chapter 9 Genetics, Genomics, Health and Disease: General Considerations
Arnold L Christianson
Chapter 10 Chromosome Disorders
Sarah Walters and Nerine E Gregersen
Chapter 11 Mendelian Inheritance
Anthony B Lane
Chapter 12 Unusual Molecular Processes that Impact on Disease
Tabitha Haw and Amanda Krause
Chapter 13 Population Genetics
Anthony B Lane and Himla Soodyall
Chapter 14 Complex Multifactorial Inheritance
Zané Lombard
Molecular Medicine
Chapter 15 Molecular Basis for Phenotypic Variation
Nerine E Gregersen and Amanda Krause
Chapter 16 Medical Genetics
Nerine E Gregersen and Amanda Krause
KEYNOTE ESSAY 3: Human Cloning: Should We Go There?
Barry V Mendelow
Chapter 17 Neoplasia: General Considerations
Alan C Paterson and Leandra Cronjé
Chapter 18 Oncogenes
Natalie A Whalley and Kate Hammond
Chapter 19 Mammalian DNA Repair
Alexio Capovilla
Chapter 20 Tumour Suppressor Genes and Inherited Susceptibility to Cancer
Kate Hammond
Chapter 21 Carcinoma
Alan C Paterson and Leandra Cronjé
Chapter 22 Leukaemias and Lymphomas
Tracey M Wiggill, Nicole S Holland, Pascale Willem and Lindsay Earlam
Chapter 23 Molecular Approaches to the Diagnosis, Prognostication and Monitoring of Cancer
Wendy Stevens
KEYNOTE ESSAY 4: Microbes, Molecules, Maladies and Man
Adriano G Duse
Chapter 24 Molecular Basis of Infectious Diseases: General Considerations
Wendy Stevens
Chapter 25 Immunology
Wolfgang Prinz, Mieneke Smit van Dixhoorn, Elizabeth Mayne and
Ahmed A Wadee
Chapter 26 Human Immunodeficiency Virus
Wendy Stevens and Maria A Papathanasopoulos
Chapter 27 Tuberculosis
Gerrit Coetzee and Hendrik J Koornhof
Chapter 28 Malaria
Theresa L Coetzer
Chapter 29 Influenza
Barry D Schoub
Chapter 30 Oncogenic Viruses
Patrick Arbuthnot
Chapter 31 Vaccines and Immunisation
Maria A Papathanasopoulos
KEYNOTE ESSAY 5: Drugs and the 21st Century
Nicole Holland
SECTION 3 MOLECULAR THERAPEUTICS
Chapter 32 Targets for Molecular Therapy: The Biology of Haemostasis
Marion Münster and Nanthakumarn Chetty
Chapter 33 Cellular Targets of Antiplatelet Agents
Nanthakumarn Chetty and Marion Münster
Chapter 34 Rational Drug Design
Grant B Napier
Chapter 35 Chronic Myeloid Leukaemia
Nerina Savage
Chapter 36 Gene Therapy
Marc S Weinberg and Patrick Arbuthnot
Chapter 37 Diabetes Mellitus
Nigel J Crowther
Chapter 38 Pharmacogenetics
Chrisna Durandt, Sahle M Asfaha and Michael S Pepper
Chapter 39 Basic Molecular Biology of Blood Groups
Wolfgang Prinz
KEYNOTE ESSAY 6: Molecular Research Case Study:
Developing Novel RNA Interference-based Therapy
Patrick Arbuthnot and Marc S Weinberg
SECTION 4 RESEARCH AND THE CONTINUING EVOLUTION
OF MOLECULAR MEDICINE
Chapter 40 Approaches to Research in Molecular Medicine
Michèle Ramsay
Chapter 41 Bioinformatics and Molecular Medicine
Andries J Oelofse and Michèle Ramsay
Chapter 42 Personalised Medicine: Dream or Reality?
Wendy Stevens
GLOSSARY
CONTRIBUTORS’ BIOGRAPHIES
SOURCE MATERIAL AND RECOMMENDED READING
PERMISSIONS AND CREDITS
INDEX

Sujets

• Molecular Biology
• Life Sciences
• Sciences et techniques
• Biology
• 454 Life Sciences
• Science

Informations

• Publié par: WITS University Press
• Date de parution: 01 janvier 2008
• Nombre de lectures: 0
• EAN13: 9781776142378
• Langue: English
• Poids de l'ouvrage: 8 Mo

Extrait

Molecular Medicine for clinicians
MOLECULAR MEDICINE for clinicians
Edited by:
B Mendelow, MB BCh, PhD, FCPath (Haematology), FRSSAf, MASSAf; M Ramsay, PhD; N Chetty, PhD; and W Stevens, MB BCh, MMed (Haematology), FCPath (Haematology)
Wits University Press
1 Jan Smuts Avenue
Johannesburg
South Africa
http://witspress.wits.ac.za
This book was supported by the South African National Health Laboratory Service (NHLS).
Text: School of Pathology, University of the Witwatersrand, Johannesburg, 2009
Graphic artwork: Marc S. Weinberg, 2008, unless otherwise indicated, 2009
Photographs: Institutes and individuals indicated, 2009
Copyright information for graphics, photographs and illustrations adapted and reproduced begins on page 495.
First published 2009
ISBN 978-1-86814-465-5
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the express permission, in writing, of both the copyright holder and the publishers.
Cover photographs:
Fibroblast cell, Dr Gopal Murti/Science Photo Library
Stethoscope, Angel Rodriguez/iStockphoto
FISH chromosomes, Pascale Willem
Cover design by Hothouse South Africa
Layout and design by Hothouse South Africa
Printed and bound by Paarl Print, Paarl, South Africa
TABLE OF CONTENTS
Foreword
Acknowledgements
Chapter 1 Introduction
Barry V Mendelow and Penny Keene
KEYNOTE ESSAY 1: Defining Who We Are: DNA in Forensics, Genealogy and Human Origins
Himla Soodyall
SECTION 1 PRINCIPLES OF CELLULAR AND MOLECULAR BIOLOGY
Chapter 2 Digital Concepts in Molecular Medicine
Barry V Mendelow
Chapter 3 The Anatomy and Physiology of the Genome
Marc S Weinberg, Natalie A Whalley and Michèle Ramsay
Chapter 4 Molecular Cell Biology
Natalie A Whalley, Sarah Walters and Kate Hammond
Chapter 5 Genetic Variation
Silke Arndt and Anthony B Lane
Chapter 6 Genes in Development
Lillian A Ouko and Michèle Ramsay
Chapter 7 Tools of Molecular Medicine
(a) Nucleic Acid Methods
Natela Rekhviashvili and Gwynneth Stevens
(b) Protein Methods
Alexio Capovilla
(c) Cellular Phenotyping and Flow Cytometry
Lesley E Scott and Debbie K Glencross
(d) Molecular Cytogenetics
Pascale Willem and Jacqueline Brown
KEYNOTE ESSAY 2: The Human Genome
Michèle Ramsay
SECTION 2 MOLECULAR PATHOLOGY
Chapter 8 Genomes and the Environment: An Overview of Molecular Pathology
Barry V Mendelow
Chapter 9 Genetics, Genomics, Health and Disease: General Considerations
Arnold L Christianson
Chapter 10 Chromosome Disorders
Sarah Walters and Nerine E Gregersen
Chapter 11 Mendelian Inheritance
Anthony B Lane
Chapter 12 Unusual Molecular Processes that Impact on Disease
Tabitha Haw and Amanda Krause
Chapter 13 Population Genetics
Anthony B Lane and Himla Soodyall
Chapter 14 Complex Multifactorial Inheritance
Zané Lombard
Chapter 15 Molecular Basis for Phenotypic Variation
Nerine E Gregersen and Amanda Krause
Chapter 16 Medical Genetics
Nerine E Gregersen and Amanda Krause
KEYNOTE ESSAY 3: Human Cloning: Should We Go There?
Barry V Mendelow
Chapter 17 Neoplasia: General Considerations
Alan C Paterson and Leandra Cronjé
Chapter 18 Oncogenes
Natalie A Whalley and Kate Hammond
Chapter 19 Mammalian DNA Repair
Alexio Capovilla
Chapter 20 Tumour Suppressor Genes and Inherited Susceptibility to Cancer
Kate Hammond
Chapter 21 Carcinoma
Alan C Paterson and Leandra Cronjé
Chapter 22 Leukaemias and Lymphomas
Tracey M Wiggill, Nicole S Holland, Pascale Willem and Lindsay Earlam
Chapter 23 Molecular Approaches to the Diagnosis, Prognostication and Monitoring of Cancer
Wendy Stevens
KEYNOTE ESSAY 4: Microbes, Molecules, Maladies and Man
Adriano G Duse
Chapter 24 Molecular Basis of Infectious Diseases: General Considerations
Wendy Stevens
Chapter 25 Immunology
Wolfgang Prinz, Mieneke Smit van Dixhoorn, Elizabeth Mayne and Ahmed A Wadee
Chapter 26 Human Immunodeficiency Virus
Wendy Stevens and Maria A Papathanasopoulos
Chapter 27 Tuberculosis
Gerrit Coetzee and Hendrik J Koornhof
Chapter 28 Malaria
Theresa L Coetzer
Chapter 29 Influenza
Barry D Schoub
Chapter 30 Oncogenic Viruses
Patrick Arbuthnot
Chapter 31 Vaccines and Immunisation
Maria A Papathanasopoulos
KEYNOTE ESSAY 5: Drugs and the 21st Century
Nicole Holland
SECTION 3 MOLECULAR THERAPEUTICS
Chapter 32 Targets for Molecular Therapy: The Biology of Haemostasis
Marion Münster and Nanthakumarn Chetty
Chapter 33 Cellular Targets of Antiplatelet Agents
Nanthakumarn Chetty and Marion Münster
Chapter 34 Rational Drug Design
Grant B Napier
Chapter 35 Chronic Myeloid Leukaemia
Nerina Savage
Chapter 36 Gene Therapy
Marc S Weinberg and Patrick Arbuthnot
Chapter 37 Diabetes Mellitus
Nigel J Crowther
Chapter 38 Pharmacogenetics
Chrisna Durandt, Sahle M Asfaha and Michael S Pepper
Chapter 39 Basic Molecular Biology of Blood Groups
Wolfgang Prinz
KEYNOTE ESSAY 6: Molecular Research Case Study: Developing Novel RNA Interference-based Therapy
Patrick Arbuthnot and Marc S Weinberg
SECTION 4 RESEARCH AND THE CONTINUING EVOLUTION OF MOLECULAR MEDICINE
Chapter 40 Approaches to Research in Molecular Medicine
Michèle Ramsay
Chapter 41 Bioinformatics and Molecular Medicine
Andries J Oelofse and Michèle Ramsay
Chapter 42 Personalised Medicine: Dream or Reality?
Wendy Stevens
GLOSSARY
CONTRIBUTORS’ BIOGRAPHIES
SOURCE MATERIAL AND RECOMMENDED READING
PERMISSIONS AND CREDITS
INDEX
Foreword
By Wieland Gevers
Emeritus Professor of Medical Biochemistry, University of Cape Town and former President, South African Society for Biochemistry and Molecular Biology.
Many people find it difficult to understand the idea of molecules (invisible to the eye, and usually detectable only by the use of complicated machines) being responsible for problems such as heart failure and mental disorders. We have evolved to trust what we can actively see, touch, smell, hear and taste; in the same way we like to understand what is going on, in our own bodies and in those of others, on the basis of direct sensory experience, developing an integrated picture facilitated by memorised information and the application of logical thinking against a background of varying amounts of emotional overdrive. That for millennia has been the basis of medicine as an art.
Molecules in contrast present all sorts of obstacles to our normal ways of addressing health issues. Compare physical anatomy with molecular structure - in the first, we can dissect cadavers with scalpels and tweezers, and see the structures and their relationships with the naked eye; in the second, the dissection requires a combination of specialised variants of optical and electron microscopy, stains and probes, and ultimately (in the present omic era) genomics, transcriptomics and proteomics, and the analysis of an endless complexity of dynamic interactions between the constituent molecules of the tissues in question.
But the shift to molecular thinking can be made quite easily, if one learns to let one s imagination habitually enter the world below one s sensory thresholds. Everything that goes wrong (and right) macroscopically is ultimately determined by what goes on sub-microscopically, and everything that happens sub-microscopically is determined by what is happening at the molecular level. The explanatory potential is accordingly usually amplified by orders of magnitude as you go down to this degree of molecular magnification. How would it be possible to discover that a host of cardiac disorders of uncertain cause are in fact caused by specific mutations in genes for proteins involved in muscular contraction and its regulation, if all we knew was what we could see, touch and feel? How would it be possible to trace the events in HIV-infected persons that are the prime causes of the phenomena observed clinically? How would it be possible to understand the workings of the immune system or the brain?
Molecular medicine therefore opens up a new world of structure and function, normal and abnormal, that can perhaps best be seen in the illustrations of textbooks such as this one, created by the integration, to temporary consensus, of knowledge laboriously harvested in countless laboratories, by countless eyes straining to see more and more of the invisible world of the molecules. Because our molecular knowledge about health and disease is still increasing by leaps and bounds, it takes considerable courage to write a textbook on molecular medicine, even when there is a good prospect of many future revised editions. Like learning to ride a bicycle, the habit of thinking in molecular terms has to be learnt, but fortunately only once; a textbook that presents a new kind of picture of the human body - of its time, unavoidably, but embedded in molecular thinking and doing - will be invaluable for many readers and students because the critical jump can be made, for ever, to a highly productive and exciting way of engaging with health and disease.
I am sure that this book will enrich the understanding and professional competence of many students and clinicians, opening gates to research careers and to improved health care at both individual and population levels. As an educational tool, it has the potential to be associated with life-changing Damascus experiences for teachers and students alike, a macroscopic catalyst for sub-microscopic and molecular insights into the human condition.
Acknowledgements
The editors would like to acknowledge their appreciation to Mr John Robertson, Chief Executive Officer of the South African National Health Laboratory Service (NHLS), for the NHLS s generous donation towards the publication costs of this textbook. His vision and commitment to the strategic expansion of knowledge in the field of molecular diagnostics have been inspiring, e