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Unlimited poweR of GenetiC
EngineerinG
Inventor’s
mouth.
Consequences of my research.
Introduction.
Mysteries in
genetic sciences.
What is
coronary artery disease?
Misconceptions in cardio-vascular
sciences.
Foundation
on which building of Baruah Applied Human.
Revolution in medical sciences rocked by
Dr.D.R. Baruah,FRCSGlas.
Unfolding the
mysteries in human genetic sciences.
Mysteries in
human genetic sciences.
How does the
mutation expresses in particular disease form?
Selection of
patients for gene analysis
Eradication of
heart disease & rarest of the rare diseases- Human genetic studies
through sequencing of m-RNA.
Signal
Transduction plays a major role during pre-bypass and post-bypass
events.
How bypass
surgery triggers signal transduction & phenotypically expressed.
Mutation
Selection of
genes causing heart & other diseases.
Hypoxia,
reactive oxygen species, intracellular calcium & Baruah syndrome.
Re-sequencing
of the following genes to identify the mysteries.
First time on
this planet– Genovac.
Baruah applied
human genetic engineering- a choice of treatment for Cancer.
TGA-A New
Method of Treatment of Complex Congenital Heart Disease.
Endocardial Cushion defect.
Genetic
Engineering–To cure the rarest of the rare autoimmune.
First time on
the Planet–Manifestation of Baruah Syndrome–Moyamoya
The rarest of
the rare genetic disorder–Takayasu.
Isolated
congenital Right Ventricular Hypertrophy.
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Applied Human Genetic Engineering - Vol.II |
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Signal transduction plays a major role
during pre-bypass and post-bypass
events
Bypass surgery is a genetically
criminal surgical procedure, injurious to heart &
health, leading to patient’s premature death. Bypass
surgery is the beginning of endless problems. I made
these statements in 1982. Till today, these statements
are unquestionable, undisputable and undebatable and
will remain in future.
It was suggested that change of life
style and food habits are the main causes which increase
the blood lipids and deposits within the arterial wall
causing luminal blockages which ultimately obstructs the
forward blood flow.
Our genetic research has proven that
these theories are baseless, here I would like to stress
the points from the findings of our genetic research
that causes of coronary artery disease before bypass
surgery, stenting or angioplasty surgery and after
bypass surgery are not similar.
Signal transduction has major &
pivotal role to play in these two dangerous situations.
External stimuli triggers the signal transduction to
trigger the whole affair. Signal transduction is a
process where external or extracellular stimuli (in form
of molecules) binds with the receptors present on cell
membrane to form a complex which triggers the
intermolecular ordered reactions to cause normal
cellular function. In this reaction, a non-mistaken
protein which is synthesized in endoplasmic reticulum
plays an important role to carry out normal cellular
function. If the external stimuli is incorrect or
mistaken one, which binds the receptors forming a new
mistaken complex and ultimately triggers the mistaken
intermolecular reactions, which ultimately synthesiszed
a protein with errors in endoplasmic reticulum and
delivers to target sites to cause abnormal mistaken
cellular function and ultimately express within
milliseconds, minutes, hours, days and years in disease
forms like ionic changes takes place within
milliseconds, protein and lipids changes takes place
within hours, days & entire bad external stimuli
ultimately brings the errors in metabolic pathways and
finally genotypically expressed which is already ordered
or triggered by mistaken signal transduction and
ultimately, phenotypically expressed in incurable
disease of particular type.
Entire ultimate functional
responsibility is held by m-RNA., which was ordered by
DNA, but actual work is done by m-RNA. It is like this-
DNA can be described as Chief of Army and RNA is
brigadier in battlefield, where brigadier only knows how
to win the battle by using his own tactics to save his
army and at the same time to defeat the enemy. It does
not necessary that he should strictly follow the order.
But generally he follows the order, but occasionally not
-depending upon the situation.
But in genetics, DNA has ordered
through m-RNA the mutations in gene to express in
disease forms. However, in the process of translation,
m-RNA ignores the new command of DNA (that is a minor
genotypic expression) and follows the routine procedure.
It means m-RNA does not want the mistaken amino acid to
synthesize so that there won’t be any ill effect and
thereby, clinically, it is not expressed in form of
disease and hence it is called as silent mutation.
However, this silent mutation can be
active when it finds favourable condition in another
generation and expressed in disease form. Favourable
condition means, interacting with other genes which
ultimately expressed in disease form. This is an active
mutation expressed clinically as a disease.
During our genetic experimentation we
found a man of 65, suffered from triple vesseled
coronary artery bypass surgery and four years later, his
symptoms recurred due to blockages of grafts and
extensive increase of blockages within the native
arteries resulting inadequate ventricular performance
required implantation of permanent pacemaker. Inspite of
having permanent pace maker, his ventricular function
has further deteriorated and cliniclly, he became
breathless on minimal exertion and unwell. We have
carried out his genomic sequences of genes and found
mutations in gene AGPAT1 and we engineered his mutated
genes with Baruah biological molecules using intravenous
route. Twenty four hours later, there was a demutations,
which continued to be unchanged. Eight days after
injection of our biological molecules, his soft plaques
from common and internal carotid arteries were
disappeared and so is the excess wall thickness of
carotid arteries and clinically, he became symptomless. Out of our surprise, he has a silent
mutation of gene responsible for cancer and but
clinically he did not have cancer. However, his twelve
years old neice, sister’s daughter is suffering from
malignant brain tumour ependymoma. (Ependymoma was
treated by surgery and radiotherapy in another hospital,
but she developed metastatic lesion in spinal chord
during treatment and primary tumour did not regress). We
have treated with our biological molecules and four
months later, ependymoma completely disappeared.
I DESCRIBE THE CORONARY ARTERY
OCCLUSION IN TWO FORMS BASED ON ITS CAUSES, which is never been thought in the
past and it is absolutely on the basis of acquired
genetical involvement and changes:
Primary
occlusion or blockages
Secondary occlusion or blockages
Primary occlusions-
This is due to
mutation of genes and its interaction with other genes.
This is normally due to stimulation of signal
transduction by external stimulus such as change of
mental status and stress. According to our genetic
research findings, it occurs at the age between 13 –16
during the period of adolescent and puberty when
physiology is changed with hormonal imbalance, change of
physiology with association of mistaken signal
transduction results mutations, dictate type & severity
of signal transduction. This is governed by external
stimulus leads to mutations of that responsible genes,
brings the errors in metabolic pathways, thereby,
synthesizing mistaken amino acids, which expressed in
diseased form.
Our experimental studies have shown
that change of mental status and stress are extremely
high at that period and we observed that it changes the
cellular morphology of the cells (from discoid to
echinoid shape, which is reversible.) These changes
occur at innumerable times during the period of
adolescent & puberty and these repetitions of changing
the cellular morphology triggers the genomic mutations
and expressed in diseased form in later date.
Repetitions of cellular morphological alterations which
are triggered by mistaken signal transduction cause
mutation of particular gene. For example, uv radiation
or diet bring measurable changes at cell membrane level,
which triggers signal transduction at intermolecular
level to bring changes at genomic level and expressed
finally phenotypically in diseased form.
Signal transduction may be small, but
intracellular effect could be larger leads to dangerous
and incurable diseases which are expressed in later
date. Change of metabolic pathways due to mutations
causing the blockages or occlusion of entire arterial
tree by depositing the subcellular calcium, lipids and
cellular debris obstructing forward blood flow. In the
reality, high blood lipids is not the dangerous
situation, but high level of intracellular calcium is
more dangerous.. This all happens during primary
occlusion.
Secondary occlusion-
I describe secondary occlusion is
caused by coronary artery bypass surgery, stenting and
angioplasty. These surgical procedures-releases number
of factors acting as external stimulus binds with plasma
membrane receptors stimulates the signal transduction
which triggers the mutation brings the errors in
metabolic pathways causing the occlusion. The process of
occlusion is the same as primary, but the triggering
stimulant is different. Bypass surgery becomes stimulant
to trigger the signal transduction immediately after the
surgery done. During the surgical procedure, oxygen
consumption to the heart becomes almost zero because of
heart is kept arrested during the procedure and coronary
perfusion is stopped by clamping the aorta above the
coronary orifices.At the end of the perfusion, coronary
arteries are reperfused by declamping the aorta.
Reperfusion of the myocardium is very dangerous at
genetic level which triggers the secondary coronary
artery occlusive disease which started in the operation
theatre before the patient comes out to ICU.
Reactive oxygen species is the major
triggering factor. Usually 5% of consumed oxygen
generates reactive oxygen species. In case of man-made
ischemic reperfusion which occurs at the end of bypass
surgery, reactive oxygen species are generated in higher
quantity which damages the cell membrane . This triggers
the accumulation of excessive lipids and eventually,
grafted conduits are blocked rapidly. In addition, lipid
deposits became rapid and more aggressive because of
same reason. It has been understood by us that premature
death is earlier in coronary artery diseased patients
those who undergo coronary artery bypass surgery than
those who are without bypass surgery. Therefore, I
stated that bypass surgery is not only mismatch surgical
procedure, but it is a surgically criminal act.
The production of large amount of
reactive oxygen species during reperfusion after bypass
surgery causes injury to myocardium leading to cell
death. It has been shown that reactive oxygen is
increased in first five minutes after reperfusion, which
causes reperfusion injury.
In healthy individuals, effect of
reactive oxygen species is nullified by several
enzymatic & non-enzymatic pathways such as superoxide
dismutases, catalase, glutathione peroxidase enzymes.
Non-enzymatic pathways include intracellular
antioxidants such as Vitamin E, C & beta-carotene,
ubiquinone, lipoic acid, urate etc. These free oxygen
radical causes mutagenesis of DNA by inducing strand
breaks, purine oxidation, protein-DNA cross linking,
which directly affects gene expression, denaturation of
proteins forming non-functional proteins. It also
affects ion channels, membrane ion pumps such as
calcium,sodium and potassium channels, sodium/calcium
exchanger which are critical for normal cardiac
excitation-contraction. It also alters activity of
sarcoplasmic reticulum calcium-triphosphatase and
reduces myofilament calcium sensitivity, both of which
are important factors in myocardial contractility.
Similar problem occurs during
stenting and balloon angioplasty, where coronary artery
perfusion is stopped.At that time, the demand for oxygen
by the myocardial cells is greater than which is not
getting because the procedure itself obstructs the
forward coronary artery blood flow even for milliseconds
and at the same time, work load of the myocardium
continues to be more during that procedure. Those events
become larger stimulus for generating reactive oxygen
species in larger quantities which triggers mutations
directly at DNA level. Due to momentary deperfusion, not
acceptable by beating ventricles with increase of
reactive oxygen species, 1-2% death due to sudden
cardiac arrest is inevitable.
 Pacemaker
is a larger stimulus for signal transduction
:
I describe implantation of Pacemaker
as symptomatic treatment of bradycardia which is harmful
to heart as it works like a whipping a tired horse to
run faster & faster till he drops dead prematurely.
Pacemaker implantation is a larger stimulus for signal
transduction, causes mutation at DNA level and affects
directly myocardium contributing to further failure and
eventually working like cardiomyopathy of dilated type,
where life is impossible to sustain further, which leads
to premature death. Permanent pacemaker is not the
treatment for removing bradycardia where after
implantation the programmer increase the amplitude to
achieve better ejection, but it never does. Therefore,
permanent pacemaker is not a life saving device, but it
is a life threatening device.
 Cancer is taking the second place for
premature death next to heart disease:
Every scientist knew that it is due
to mutation at DNA level but the causes of mutations are
not clearly understood. Many theories have been
postulated. But none of the theories are working till
now for actual cause and its permanent remedy. Some of
the genes are identified causing some types of cancers
and some are yet to identify. Gene therapy is not
encouraging procedure due to its inherent drawbacks and
at the same, it has never been successful in the past.
Therefore, practice of gene therapy is obsolete.
In recent years stem cell therapy is
known to be playing a larger role in the treatment of
cancer. However, I suspect that the fate of stem cell
therapy will not be same as the fate of gene therapy.
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Copyright© DR Dhani Ram Baruah Heart City2007
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