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CELL, GENE AND MOLECULAR
THERAPY:
NEW CONCEPTS

No part of this digital document may be reproduced, stored in a retrieval system or transmitted in any form or
by any means. The publisher has taken reasonable care in the preparation of this digital document, but makes no
expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No
liability is assumed for incidental or consequential damages in connection with or arising out of information
contained herein. This digital document is sold with the clear understanding that the publisher is not engaged in
rendering legal, medical or any other professional services.
CELL, GENE AND MOLECULAR
THERAPY:
NEW CONCEPTS

VIROJ WIWANITKIT

Nova Biomedical Books


New York
Copyright © 2009 by Nova Science Publishers, Inc.

All rights reserved. No part of this book may be reproduced, stored in a retrieval system or
transmitted in any form or by any means: electronic, electrostatic, magnetic, tape, mechanical
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Telephone 631-231-7269; Fax 631-231-8175
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NOTICE TO THE READER


The Publisher has taken reasonable care in the preparation of this book, but makes no expressed
or implied warranty of any kind and assumes no responsibility for any errors or omissions. No
liability is assumed for incidental or consequential damages in connection with or arising out of
information contained in this book. The Publisher shall not be liable for any special,
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and copyright is claimed for those parts to the extent applicable to compilations of such works.

Independent verification should be sought for any data, advice or recommendations contained in
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to persons or property arising from any methods, products, instructions, ideas or otherwise
contained in this publication.

This publication is designed to provide accurate and authoritative information with regard to the
subject matter covered herein. It is sold with the clear understanding that the Publisher is not
engaged in rendering legal or any other professional services. If legal or any other expert
assistance is required, the services of a competent person should be sought. FROM A
DECLARATION OF PARTICIPANTS JOINTLY ADOPTED BY A COMMITTEE OF THE
AMERICAN BAR ASSOCIATION AND A COMMITTEE OF PUBLISHERS.

LIBRARY OF CONGRESS CATALOGING-IN-PUBLICATION DATA

Viroj Wiwanitkit.
Cell, gene, and molecular therapy : new concepts / Viroj Wiwanitkit.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-60741-682-1 (E-Book)
1. Therapeutics, Experimental. 2. Cellular therapy. 3. Immunotherapy. 4. Gene therapy. I. Title.
[DNLM: 1. Therapeutics. WB 300 V821c 2009]
RM111.V57 2009
615.8'95--dc22
2008047192

Published by Nova Science Publishers, Inc. Ô New York


CONTENTS

Preface vii
Chapter I Basic Principle of Medical Treatment 1
Chapter II Nanotherapy 13
Chapter III Quantum Therapy as Well as Photon Therapy 31
Chapter IV Tissue Engineering and Medical Biopolymer Application 43
Chapter V Transplantation in Medicine 55
Chapter VI Advent in Radiotherapy, Radiointervention and Radiosurgery 69
Chapter VII Stem Cell Therapy 83
Chapter VIII Advent in Transfusion Medicine 95
Chapter IX Phototherapy 109
Chapter X Gene Transfer and Gene Therapy 121
Chapter XI Immunotherapy 133
Chapter XII Therapeutic Vaccination 147
Chapter XIII Chaperone 159
Index 165
PREFACE

Treatment is the heart of medicine. For patient, the main aim of visiting to the physician
is to get the best therapy. Therapy has a long history. At the present, advanced biotechnology
help improve the medical treatment. Apart from the classical treatment, there are many new
emerging means of medical treatment. In this book, the concept of new therapeutic channels,
cell, gene and molecular concepts will be focused. Interesting details on concepts for these
modern therapies can be found in this book and this book can be the reference resource for
the physician, medical personnel and health care worker for update the knowledge of
treatment.
Chapter I - Health is the best wealth. Everyone requires good health to maintain his/her
daily life. In general, everyone will be healthy if there is no external or internal insult to
disturb his/her normal physiological function. There are several possible insults that can bring
problem to one’s health. The insult can be biological, chemical or physical. Examples of
biological insults are pathogen, germ, parasite, organic substances and etc. Examples of
chemical insults are chemical substances and toxins. Examples of physical insults are
electrical power, mechanical power, radioactive power and etc.
For developing an overt abnormality, there will be a classical process. Molecular or
submolecular changes will accumulate to form a biochemical change. Biochemical changes
will accumulate to form a physiological change. Physiological changes will accumulate to
form an anatomical change. Anatomical changes will accumulate to form overt abnormality.
This step by step process is the core concept in medicine. This concept is also applicable to
the concept of advanced bioinformatics. To study on a disease, probing to a wide range on its
pathogenesis can be done by modern bioinformatics concept. From gene to protein to
expression can be manipulated. Geneomics makes use of genome data to explain genomic
phenomenon. Proteomics makes uses of proteome data to explain proteomic phenomenon.
There are also other “omics” sciences that can be used. The other omics sciences are
transcriptomics, metabolomics, cytomics and etc. If readers feel interested on these new
omics sciences, suggestion is made for reading textbook on bioinformatics science.
Focusing on the work “disease”, it covers a wide range of disorders. Disease is usually
used for describing any overt abnormalities. Disease usually means any conditions that need
proper medical management or treatment. It should be noted that some abnormalities,
especially for those in molecular level change, will not be called disease. Healthy in general
viii Viroj Wiwanitkit

means no disease. However, as previously mentioned, molecular level abnormalities can be


existed and this brings the stage of pre-disease or risk. The current concept in medicine
moves to prevention rather than treatment. In preventive medicine, finding for risk is
necessary and proper management on identified risk must be done.
The study of the relation of man to his/her environment in developing countries
emphasizes the inevitable need for societies to know the true causes of infection,
malnutrition, and poverty. The requirement is for improvement in the quality of human life in
less developed nations, a recommendation easy to prescribe but hard to accomplish. The
present focus includes the relation between economic and other factors in health
development. This interpretation has been selected for the acceptance of a disciplinary
approach in the commissioning of papers might have the unintended effect of excluding some
key areas of study, which makes use of the consideration of crucial interrelationships
between disciplines. Nutrition as a discipline evolved out of medical and bio-chemical
concept on the relation between food and health. Until the 1950s nutrient deficiencies
dominated the nutritional track of analysis. From this moment attention was further led to
nutritional consequences of the welfare state. The interrelation between health, nutrition and
welfare is complex.
Chapter II - Nanotechnology is a modern technology covering to management,
construction, synthesis of devices in atomic or molecular level that has its the size between, 1
and 100 nanometers. The nanodevice has its special function in physical, chemical and
biological aspect that can be adapted for usage. Nanotechnology is the application of
knowledge on nanoscience. Nanoscience is a modern science covering on the natural fact of
nanolevel conditions. Nanoscience focuses on three main scientific areas: physical, chemical
and biological sciences. The main fundamental knowledge for the beginner in nanoscience is
what nanolevel is. “Nano” is a modern scientific work describing for the 10-9 level. The
nanolevel is minuteder or fewer than microlevel (micro = 10-6). Nanotechnologies can assist
practitioner diagnosis at the single-cell and molecule levels, and some can be adapted in
current molecular diagnostic methods, such as biochips. Nanoparticles, such as gold
nanoparticles, silver nanoparticles and quantum dots, are the most broadly used, but various
other nanotechnological devices for manipulation at the nanoscale as well as nanobiosensors
are also promising for potential clinical applications. In conclusion, nanotechnologies will
expand the borders of current molecular diagnostics and assist in point-of-care diagnostics,
integration of diagnostics with therapeutics, and modern construction of personalized
medicine. Jain mentioned for the emerging role of advances in biochip and microarray
technologies in the modern construction of personalized medicine. Jain proposed that
biochips such as GeneChip, CYP450, electrochemical biochips, protein biochips,
microfluidic biochips and nanotechnology-based biochips played a significant role in
molecular diagnostics, and their application in point-of-care diagnosis is expected to facilitate
the modern construction of personalized medicine. Although the potential diagnostic
applications are wildly expanded, the most important current applications are limited in the
areas of biomarker discomuch, cancer diagnosis, and determination of infectious pathogens.
Chapter III - Quantum is a physical term that implies the smallest discrete amount of
some physical property that a system can have. Quantum theory, the branch of physics which
is based on quantization, started in 1900 when Planck published his theory explaining the
Preface ix

emission spectrum of black bodies. The bippoasesic of radiation as well as matter is the heart
of the quantum theory. In physics, quantum mechanics is the learning of the relationship
between energy or radiation as well as matter, in particular that between valence shell
electrons as well as photons. Bohr’s theory is the root for the generation of the present
quantum physics. Bohr's atomic theory is broadly viewed as remarkable, both for its accuracy
in predicting the observed optical transitions of one-electron atoms as well as for its failure to
fully correspond with current electronic structure theory. However, what is not routinely
appreciated is that Bohr's classical semiclassical conception differed significantly from the
Bohr-Sommerfeld theory as well as offers an alternative semiclassical approximation scheme
with remarkable attributes. It is routinely believed that the old quantum theory, as presented
by Bohr in 1913, fails when adapted to few electron systems, such as the H(2) molecule.
Bohr's classical method did not impose action quantization constraints but rather obtained
these as predictions by simply matching photon as well as classical orbital frequencies. The
discovery of the efficacy-quantum by Planck as well as further work of Borh was the
fundamental contributing root to Einstein's hypothesis of lightquanta. With the mentioned
fundamental theories, Einstein could explain the external light-electrical effect. The work of
Einstein is the root of the modern ppoasese of science. As a case study, there was a long track
from the concept of stimulated emission as the fundamental idea of laser technical work by
Albert Einstein in 1917 to the practical use of the laser are present. It is also the fundamental
for the modern science, quantum mechanics. Quantum mechanics is a fundamental branch of
physics with wide applications in both experimental as well as theoretical physics. The
quantum theory is the theoretical basis of modern physics that can be valuable in explaining
the nature as well as behavior of matter as well as energy on the atomic as well as subatomic
level. Conrad said that biological cells had greater information processing efficiency than the
programmable computers used to model them. Conrad also suggested that systems in which
quantum features played a prominent work are more powerful than classical physical-
dynamical analogs.
Quantum medicine is the modern kind of medicine. Naturally, all things, chemicals,
plants, animals as well as human beings are composed of various tissues, organs, cells,
molecules, as well as atoms. The combinations of atoms lead to molecules. The combinations
of molecules lead to cells. The combinations of cells results in tissues. The combinations of
tissues lead to organs. The combinations of organs lead to human beings. Fundamentally, an
atom consists of electron as well as nuclei which intern quantum as well as neutron. Electron
poses negative charge, proton poses positive charge as well as neutron poses neutral charge.
Normally human beings cannot see the atom. In addition, the compositions of atom are
beyond human reach. But according to the modern elementary particle theory, elementary
particle is considered to have immense size as well as types, as well as it poases property as
energy field which rotates as well as vibrates itself. With the advent in nanoscience, those
very tiny compositions can be studied.
Quantum determination method is the determination technique, which tests the energy
composed of magnetic energy generated by quantum as well as electron movement.
Improvements in quantum chemical techniques have led to increased applications to
biological problems, including the generation of potential energy functions for molecular
mechanics as well as modeling of the reactive chemistry in enzyme active sites, with
x Viroj Wiwanitkit

particularly interesting progress being constructed for metal-containing systems. The three
items to be considered in quantum determination method are (a) use of quantum mechanical
electronic structure techniques such as molecular orbital theory as well as density functional
theory, usually in conjunction with molecular mechanics; (b) treating vibrational motions
quantum mechanically, either in an instantaneous harmonic approximation, or by path
integrals, or by a three-dimensional wave function coupled to classical nuclear motion; (c)
incorporation of multidimensional tunneling approximations into reaction rate calculations.
Orbital theory is the fundamental knowledge for quantum chemistry. Molecular orbital
analytical work is the fundamental technique for study of quantum mechanical electronic
structure. To assist molecular orbital analytical work, there are several modern computation
instruments for performing this analytical aim. As a case study, AOMix is a modern user-
friendly software for the molecular orbital analytical work. It calculates the molecular orbital
compositions in terms of the constituent chemical parts in the molecule or atom. AOMix
automatically processes output files of multiple quantum-chemical packages. AOMix also
permits to deeply review chemical structure making use of overlap populations (total as well
as per molecular orbital), valence indices, 2-center (Mayer, Lowdin, Wiberg, as well as bond-
order symmetry components) as well as 3- as well as 4-center bond orders, charge
decomposition orbital, CDA (total, per molecular orbital, per symmetry type), as well as
condensed Fukui functions. Conventional quantum chemistry techniques are either too
expensive to apply to large systems or too approximate for the results to be reliable, as well
as they fail to satisfy this requirement. A variety of different approaches is being developed
with the aim of achieving this goal: local correlation techniques; divide-as well as-conquer
techniques; linear-scaling density functional techniques based on the fast multiple as well as
other approximations; effective potential techniques; as well as hybrid techniques.
The influence as well as application of quantum determination on medical field is named
“quantum medicine”. Quantum medicine is one of the most promising tracks of modern
contemporary medicine. It is based on the use of aimful effects of low-dosage
electromagnetic radiation or quantum in treatment, diagnosis, prophylaxis, as well as
rehabilitation of patients.
Chapter IV – Engineering is a specific science that focuses mainly on the physical aspect.
There are man fields of engineering at present. For example, electrical engineering is a
specific branch of engineering dealing with electricity. However, due to the concept of
convergence of science, engineering becomes emerged with biological science. Application
of engineering in biological science helps jump across the inter-science barrier and brings
new advent to the world population. For example, merging between computational
engineering and genetics biology brings new science called genomics [1-3], which is the
modern blooming science at present. Nanoengineering plus medicine forms nanomedicine
which is another present new hope of the world for global health development.
Application of engineering on biology helps explain and manipulate difficult biological
question. This can be applied in medicine, which is a branch of biological science. Special
forms of medical applications can be seen. One of the most famous application is medical
engineering. This involves medical instrumentation as well as other applied engineering for
medicine. As mentioned, the usefulness of application of engineering in medicine is very
much. It helps from diagnosis, treatment and prevention. In this book, the author focuses
Preface xi

content on treatment, therefore, treatment will be focused and applied engineering for
treatment in medicine will be mentioned. An important therapeutic application is tissue
engineering and medical biopolymer science. The application is useful for reconstructive
medicine. Specifically, medical biopolymers are presently used in dentistry and orthopedics.
With these applications, it can help manage previously untreatable diseases and conditions.
Further details will be further discussed.
Chapter V - When an organ lost, it is necessary to get medical management. Organ lost
usually means lost of function. In severe case, organ lost ends up with death. There is no
method to recover in the past and this has been continuously searched for the solution.
Transplantation is a new concept using the replacement of the lost organs by the new ones.
New ones means new organ from the others. Therefore, it means transferring of one's organ
to another. This is ethical concern and new concept in medicine. Indeed, organ
transplantation has long history. More than 50 years are recorded. Learning of history of
transplantation is necessary to allow us to appreciate the great potential offered by current
biomedical science and engineering for future developments in the therapies of this more than
natural practice. At present, embryonic stem cells are used in the studies of the differentiation
of various cells or tissues for transplantation therapy, because of their pluripotential property
to differentiate into almost all types of cells in the body.
Chapter VI - Radioactive substance is classified as a new group of elements that human
beings knew for about 1 century. After the discovery of Curie Family, radioactive substance
becomes on focused interested of global scientist. There are many researches on radioactive
substance. Application of radioactive substance for usage is continuously proposed. At
present, radioactive substances can be used in industry as well as medicine. The main focus
of radioactive use in medicine is for treatment of tumor. Also it is applied for diagnosis as
radioassay.
Parallel to radioactive substance, rays are also focused for its application in medicine.
After the discovery of X-ray, the application in medicine is a big jump of medical world.
With use of X-ray, physician can visualize the internal structure of human being and used it
for diagnosis. This is the history of development of a famous medical science, radiology. At
present, radiology is a necessary medical science that helps both diagnose and treat of
patients. Radiology unit is a basic unit for all hospital. Basically, three basic main branches of
radiology are described as radiodiagnosis, radiotherapy and nuclear medicine. Radiodiagnosis
focuses mainly on diagnosis of disorders by usage of several means of imaging technology in
medicine. Radiotherapy focuses mainly on treatment and will be mainly detailed and
discussed in this chapter. Finally, nuclear medicine focuses mainly on both diagnosis and
treatment based on usage of radioactive substances. Important details of nuclear medicine
based treatment will also be detailed and discussed in this chapter.
Chapter VII - "God made the sun. God made the moon. God made the star." These
sentences are basic principle for Christian. Living things in the worlds started for many
million years ago. Nobody can tell the exact starting point of time for life. Life is complex.
Generation of living thing is a very complicated process and no present high technology can
work this. Natural makes life. This can be said that god made life. Due to Buddhism, life can
be generated if there are fulfill criteria. as a) father and mother have sexual intercourse, b) the
time is proper and c) there must be specific superstitious spirit for this condition. This is the
xii Viroj Wiwanitkit

fact. There must be gametes from both mother and father for fertilization. In human,
beginning of new lie is widely studied. After fertilization, development process in utero is
continuous. Embryonic generation is a developmental process for all human beings.
Everyone in this world had to pass this step before birth. Further process as passing from
embryo to fetus is the next step in utero. Birth is the finalized process for in utero processes
and this is the starting point of human status.
Considering the embryonic period, the generation of cell and tissue is the main hallmark
activity. Of several processes, first sign of life, movement, can be seen at the third month
after fertilization. For cell and tissue growth, basic promoter as stem cell is required. Stem
cell is the basic cell generator of other cells and tissues. This is also the important step in
development for starting of complete life. Stem cell has its main function during in utero
period. However, some stem cell is still existed and functional in full term human life. This
can be seen in bone marrow, which is the source of generation of blood cell in circulation. It
is accepted that blood cell must be generated all times thorough the life of human beings.
Harvesting stem cell for medical use is the present focus. It can be important and applied for
treatment process of some previously untreatable diseases. Stem cell technology could also
be a significant helpful tool for an understanding on early human developmental process and
screening potential candidates for new drug search.
Chapter VIII - There are many basic case groups to receive extensive blood transfusions
including the cases in intensive care unit, thalassemic cases, acute blood lost cases as well as
traumatic cases. Approximately four-fifth get multiple transfusions. At present donor
exposure is an issue because transfusion risk is still apparent. Gived blood should be applied
for the treatment of cases as well as poses well asled with the same serious respect as well as
ethical stas well asards as with which it was gived by the donor. Directed donor or
purcposesed system should not be encouraged. Anonymous donation should be applied. As a
rule blood msut be given as a gift with no reimbursement as well as should be applied to an
unknown case with the intention to help as well as not to harm. Donation shall be easy as
well as secure for the donor. Therefore, blood shall be poses well asled with respect as well
as should be applied with the intension to treat cases as previouly stated. Promotion of the
blood donation is the topic. Owing to a recent study, the principal obstacle for blood donation
is fear owing to poor knowledge.
Gived blood have to be applied for treatment of case directly or indirectly. Direct help to
the case might be transfusion of single units or transfusion of units from a batch, platelets or
plasma outcomes. Indirect help to the case include using of a few tubes for laboratory
controls or many units for stas well asards with the intention to help cases to set normal
values for a new test which is useful for laboratory medicine. Use of gived blood for other
aims than transfusion have to be no specific information when blood is applied as laboratory
quality controls but information for other kinds of use as well as assure for no identification
at the pposese of informed consent with identification of donor is needed.
Chapter IX - Light is a basic thing that human beings know. Light is mainly from the
sun. Electricity can also provide light. Therapy by light is also a medical concept. Since light
poses energy therefore it might be used for treatment. In this chapter, the author will present
the topic on phototherapy. Main kinds of application, photodynamic therapy and classical
phototherapy for newborn will be discussed.
Preface xiii

Chapter X - At the starting point of this century genetics arose out of developmental
history as the science of the reasonable understanding of development. The concept of the
difference between the possibility for a trait and the trait proper, between the genotype and
the phenotype, was clear only during the first decade of the century. After Spemann's epochal
discovery, who already rewarded with the Nobel Prize in 1935, of the organizer and the
beginning of the experimental analysis of developmental fields, little or no progress was
derived until the last few years when a new emerging revolution appeared in developmental
biology. The classical point of view prevailed into the 1930s, and conceived the gene as an
indivisible single item of genetic transmission, recombination, mutation, and function. The
discovery of intragenic recombination in the early 1940s and the setting of DNA as the
physical basis of inheritance resulted in the neoclassical concept of the gene, which prevailed
until the 1970s.
In the past, studying of the gene is not easy but very difficult. Genetic laboratory seems
to be a complex and mysterious field. The discoveries of DNA technology, beginning in the
early 1970s, have resulted in the second revolution in the concept of the gene in which none
of the classical or neoclassical criteria for the definition of the gene hold extremely true.
These are several new findings concerning gene repetition and overlapping, movable genes,
complex promoters, multiple polyadenylation sites, polyprotein genes, editing of the primary
transcript, pseudogenes and gene nesting. Introduction of Southern, Northern and dot blotting
and DNA sequencing later in the 1970s considerably improved the diagnostic capabilities.
Nevertheless, it was the new finding of the polymerase chain reaction (PCR) in 1985 that
resulted in an exponential blooming in molecular biology and the introduction of practicable
nucleic acid tests in the routine laboratory. Blooming of molecular biology leads to several
simplified techniques for genetic studying. Finding amino acid sequence of a gene can be
easily done by basic sequencing technique.
Chapter XI – The word immunity is a basic medical word describing a specific system of
human beings. Immunity is a specific system dealing with the defensive mechanism.
Everyday, human body has to expose to several alien foreign bodies and some of these alien
foreign bodies are harmful and needs proper management. Immunity plays important roles for
this overall process. Considering defensive mechanism of human beings, there are 2 main
parts immunity and non-immunity portions. Non-immunity portion is a non specific process
and usually firstly act to any alien foreign bodies. Examples of non specific process are
mucous barrier and several reflexes. Considering immunity, it is a specific process. The
hallmarks of immunity consists of memory and specificity, therefore, the first exposure
cannot generate immunity. The immunity process can be divided into two main parts:
humoral mediated immunity and cellular mediated immunity. Humoral medicated immunity
makes use of humoral substance, antibody for action. Whereas cellular mediated immunity
makes use of cells, blood cells, for action. Of several cells in blood stream, lymphocyte, T
cell, B cell and nonTnonB cell, are mentioned for cellular mediated immunity. These main
kinds of lymphocytes take important role in cellular immune process. T cell takes role for
generation of cytokine whereas B cell takes roles in antibody generation process.
As mentioned, immunity plays main roles in defensive mechanism. When a foreign body
enters into human body and pass non specific immune defensive mechanism process, it will
be further reacted by immunity. Destruction of foreign body can be seen via antibody system
xiv Viroj Wiwanitkit

with help of compliment or via cell mediated immunity process with help of cytokine. With
complete full function of immunity, pathogens or foreign bodies can be successfully
destroyed. However, in some cases, those aliens can conquer immune system process and this
will result in pathological conditions or diseases. Good examples are infections. With
complete perfect immunity, human will be helpful. However, extremely high immunity
process or hypersensitivity can be problematic. On the other hand, extremely low immunity
process of immunity or immunodeficiency can also be problematic.
Chapter XII – Vaccine is a specific important tool in medicine. Due to the principle of
immunity, human beings require immune to defend any alien foreign bodies. However,
immunity cannot be functional if there is no previous exposure. This means it has to be a
memory before immune generation or the human beings must experience previous foreign
bodies’ invasion. However, in some cases, immunity is slightly generated and cannot fight
with external invasion of align foreign bodies and this brings mortality and morbidity.
Therefore, simulating the invasion of align foreign bodies to prepare for real invasion is
needed and very useful. This is the concept of vaccination. Vaccination is defined as a
primary prevention. Vaccine can prevent before real existence. Vaccine is a mode of
simulating interaction as previously described.
Vaccination is classified as an active immunization. This means tit makes uses of human
beings physiological process to create immune by itself. There are several vaccine at present.
Recommendation for vaccination might be different in different settings. Expanded Program
on Immunization (EPI) is the basic public health one in all countries. With use of vaccine,
controls of many infectious diseases are feasible. Pox is an example of infectious disease that
can be controlled by vaccine. This infection is already got rid of by succeed in global
vaccination. The presently widely used vaccine include rabies vaccine, measles vaccine,
rubella vaccine, Japanese encephalitis vaccine, hepatitis B vaccine, hepatitis A vaccine,
influenza vaccine, varicella vaccine, pneumococcal vaccine, pertussis vaccine, diphtheria
vaccine, BCG and toxiod. However, at present, there are attempts to develop more vaccines
for real clinical usage/. This is the aim of preventive medicine. In addition, there are attempts
to develop vaccine for expanded usefulness. This is the origin of therapeutic vaccine. This is
the new trend to use vaccine as treatment tool. This is classified as immunotherapy. The
details of this new way of immunotherapy will be further detailed and discussed in this
chapter. To produce a therapeutic vaccine, it might be a basic knowledge on biotechnology
and immunology. More details on this item can be seen in this chapter.
Chapter XIII - Terminology, chaperone means an adult who takes care of one or more
unmarried men or women during social occasions. But this is not the medical specific
meaning. In medicine, chaperone therapy is a new concept. Helping or assisting on other
molecules is also the ways that chaperone acts. This term is primarily used in molecular
biology. “How do chaperones operate in cells?” is a big scientific question. Saibil said that
recent advances were giving an improved understanding of the nature of chaperone
interactions with their non-native substrate proteins.
Burston and Clarke said that chaperones could be broadly defined as proteins which
interact with non-native states of other protein molecules and this activity was significant in
the folding of newly synthesized polypeptides and the assembly of multisubunit structures;
the maintenance of proteins in unfolded states fit for translocation across membranes; and the
Preface xv

stabilization of inactive appearances of proteins which are switched on by cellular signals;


and the stabilization of proteins unfolded during cellular stress. Hartl said that different types
of molecular chaperones, such as the members of the Hsp70 and Hsp60 families of heat-
shock proteins, participate in a coordinated pathway of cellular protein folding.
Basically, Hsp70 proteins are central components of the cellular network of molecular
chaperones and folding catalysts and these proteins could help a large variety of protein
folding actions in the cell by transient relation to their substrate binding domain with short
hydrophobic peptide segments within their substrate proteins. Hsp90 is another molecular
chaperone related to the folding of signal-transducing proteins, such as steroid hormone
receptors and protein kinases. Hsp90 contributes to several discrete subcomplexes, each
having distinct groups of co-chaperones that function in folding pathways. Wegele et al. said
that the chaperones Hsp70 and Hsp90 might have a function in the folding and maturation of
key regulatory proteins, like steroid hormone receptors, transcription factors, and kinases,
some of which were related to cancer progression. They noted that Hsp70 and Hsp90
construct a multichaperone complex, in which both are jointed by a third protein called Hop
and such connection of and the interplay between the two chaperone machineries was of
significant importance for cell viability. Callebaut et al. noted that domain III, common to the
hsp60s and hsp70s was also found in the hsp90s and adopts a beta-alpha-beta Rossmann-
folded structure which was enrolled in the NAD-binding domain of dehydrogenases. They
noted that the hsp molecules could act as unfoldases by disrupting secondary structures
through redox reactions on the main polypeptidic chain with which these molecules interact.
Chapter I

BASIC PRINCIPLE OF MEDICAL TREATMENT

HEALTHY AND DISEASE

A. General Concept

Health is the best wealth. Everyone requires good health to maintain his/her daily life. In
general, everyone will be healthy if there is no external or internal insult to disturb his/her
normal physiological function. There are several possible insults that can bring problem to
one’s health. The insult can be biological, chemical or physical. Examples of biological
insults are pathogen, germ, parasite, organic substances and etc. Examples of chemical insults
are chemical substances and toxins. Examples of physical insults are electrical power,
mechanical power, radioactive power and etc.
For developing an overt abnormality, there will be a classical process. Molecular or
submolecular changes will accumulate to form a biochemical change. Biochemical changes
will accumulate to form a physiological change. Physiological changes will accumulate to
form an anatomical change. Anatomical changes will accumulate to form overt abnormality.
This step by step process is the core concept in medicine. This concept is also applicable to
the concept of advanced bioinformatics. To study on a disease, probing to a wide range on its
pathogenesis can be done by modern bioinformatics concept. From gene to protein to
expression can be manipulated. Geneomics makes use of genome data to explain genomic
phenomenon. Proteomics makes uses of proteome data to explain proteomic phenomenon.
There are also other “omics” sciences that can be used. The other omics sciences are
transcriptomics, metabolomics, cytomics and etc. If readers feel interested on these new
omics sciences, suggestion is made for reading textbook on bioinformatics science.
Focusing on the work “disease”, it covers a wide range of disorders. Disease is usually
used for describing any overt abnormalities. Disease usually means any conditions that need
proper medical management or treatment. It should be noted that some abnormalities,
especially for those in molecular level change, will not be called disease. Healthy in general
means no disease. However, as previously mentioned, molecular level abnormalities can be
existed and this brings the stage of pre-disease or risk. The current concept in medicine
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