DR. BARUAH HEART CITY

                                                                                                   

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                 ACITY OF HUMAN GENOME A INSITUTE OF APPLIED HUMAN GENETIC ENGINEERING CITY OF KNOWLEDGE NOT MADE OF BRICKS & MORTAR

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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

UNFOLDING THE MYSTERIES OF GENETIC SCIENCES IN INCURABLE DISEASES LIKE CORONARY ARTERY DISEASES, CANCER, & RAREST OF THE RARE DISEASES LIKE MOYAMOYA, SLE, TAKAYASU ETC.

 

 

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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