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WILLIAM FREDERICK KOCH, PH. D., M.D
NEOPLASTIC AND VIRAL PARASITISM Their Basic Chemistry And Its Clinical Reversal NEOPLASTIC AND VIRAL PARASITISM THEIR BASIC CHEMISTRY AND ITS CLINICAL REVERSAL By WILLIAM FREDERICK KOCH, PH. D., M.D. Copyright by Wm. F. Koch, Ph.D., M. D.
The research that is being offered now was started 50 years ago with the writer’s discovery that complete parathyroidectomy resulted in the production of fatally toxic quantities of guanidine and methyl guanidine in the tissues and their excretion in the urine. (1) Three years later Paton of Glasgow fully confirmed this finding. (2) We wish to show now that the data gathered from this study led to a clinically useful concept about energy production in the tissue cell and its transfer to the functioning elements to support contraction, secretion, conduction and cell division. The atomic exchanges and the electronic displacements that take part appear to follow a pattern of construction and activity which one identifies in the normal functioning mechanism and also in the natural pathogens and which accounts for the properties of viral parasitism. This pattern also guides the construction of the agent used to reverse the pathogenesis and correct the parasitism in viral and neoplastic diseases — a sort of a Least Common Denominator. The facts and conclusions were assembled at first as a Postulate but, now that they are confirmed by their clinical utility, they form the basis for a new Therapy. This research did not follow the usual lines of thought that govern current therapeutics, for it is based on the properties of the free radical, the double bond and the Carbonyl and azomethine groups. Such matters have not interested medicine heretofore, though they are the fundamental chemistry of the great industries including the plastic industry. But now (June, 1961) that Szent Gyorgyi suggested that future cancer research might do well to learn if the “lone electron” (free radical) played a part, a general interest in the science that is basic to our Thesis has been created and we are, therefore, obligated to make this disclosure. This report should stimulate or interest biologists and physicians to broaden their approach when meeting their unsolved problems.
First let us consider what complete parathyroidectomy revealed as a guide to this study. In addition to the guanidine bases, excessive amounts of lactic add, phosphate and calcium were eliminated in the urine in spite of forced ventilation of the lungs. It was, therefore, apparent that fermentation supplanted oxidation as a source of energy for function. The autopsies showed extensive ante-mortem dotting of the blood in the large veins and in the tissues and a hemorrhagic glomerulitis and hepatitis. After kidney and liver functions were destroyed, the convulsions were more severe and soon proved fatal.
We attribute the high toxicity of the guanidine structure to its activated amine group as conjugated with the imide group by which it was relieved of a quota of inactivating electrons. The reaction we are most interested in here is the ability of an activated amine group to condense with a Carbonyl group to form an azomethine double bond, which physiologically serves as an “avenue of electrons” or bridge for energy transmission, in our opinion, and is readily formed or split by hydrolysis at physiological levels. Pathologically, the bond is stable against hydrolysis at physiological levels and, hence, interferes with important Carbonyl functions. Though it has attracted little attention in biology it is present, once or more often, in most of the vital molecules in tissue chemistry and recently is assigned a place by Braunstein and Kritzman in the co-factoring of transaminations by pyridoxal phosphate. Its remarkable properties have fulfilled the requirements of our Concept, long before it was considered in biochemical processes. It is now known that guanidine destroys the Pasteur Effect. This is what happened in the parathyroidectomized dogs and our Thesis claims that the Pasteur Effect is governed by the Carbonyl group that initiates oxidations for energy production. (3) This group we designate the Functional Carbonyl Group of energy production, the FCG, which is inactivated by condensing with guanidine, whereby energy production is blocked. On the other hand, the amine group of creatine, methyl guanidine, acetic acid, is also activated by conjugation with the imide group of the guanidine fraction, but because of the influence of such substituents as methyl and acetic acid, its condensations with Carbonyl are very liable to hydrolysis, so it is not toxic and can serve important physiological functions. We assign it an accessory place in carrying out the Pasteur Effect. The ante-mortem clots in the large veins showed that fermentation and the Krebs Cycle oxidations progressing in the tissue fluids were not sufficient to charge the surfaces of the blood and tissue colloids for good dispersion, so the blood jelled in consequence. It must be recalled that an ante-mortem clot is not a true fibrinous clot, but a jelly-like change due to lack of electric charges on the colloidal surfaces and indicates a defect in the energy production by the oxidation mechanism, aside from energy carried by ATP. Jelling of the blood in the coronary or cerebral vessels blocks the circulation in the early part of an apoplectic stroke or coronary occlusion attack not caused by direct embolism. In such instances, the oxidations within the functional elements that provide the energy for good dispersion of the colloids are blocked. In the parathyroid studies, guanidine was the blocking toxin and its injection in toxic doses produced all the changes that follow parathyroidectomy, including ante-mortem clots. Because of the properties of the activated amine group and the evidence that the tissue oxidations were blocked, we concluded, that the functional oxidations are initiated by dehydrogenation accomplished by highly activated Carbonyl groups of the functional mechanism — the Functional Carbonyl Group (FCG). The activation, we concluded from additional observations, was due to its conjugation with electron contributing double bonds of an ethylenic linkage, which would lose this power by making additions with free atoms or radicals. Because of clinical encounters, it was necessary to assume that a Functional Carbonyl Group received the energy produced by the oxidations initiated by the FCG of energy production, for if this FCG of energy acceptance was blocked bycondensing with a firmly binding amine, the functional elements would be under energy starvation and function would be blocked just as much as if energy were not produced. So we Postulated that if the energy evolved at the FCG of energy production could pass via an azomethine bridge into the mobile electrons of an amine rich in double bonds and this amine could split off from the FCG at physiological levels, it could carry its energy to the FCG of energy acceptance and release it for function. For clinical purposes this is all we needed to assume to explain the two possible types of functional block — that is due to failure to produce energy, and that is due to failure to pass the energy into the functional units. The blocking would be by firm azomethine condensation, or by an addition of a free radical to the activating double bonds of either FCG, as previously stared.
After 1930 when Lohmann exposed the function of creatine phosphate (4) and Lundsgaard showed its relation to muscle contraction, it was easy to fill in our Thesis as follows, especially after Englehardt (5) demonstrated in 1939 that ATP (adenosin triphosphate) gave up its energy to support the contraction of muscle fibrillae. We assumed that the FCG of energy production dehydrogenated fuel or pathogens that entered its field. As soon as the acquired hydrogen atom was removed by some cofactor, the FCG condensed with the amine group of creatine to pass energy into its mobile electrons, until it was sufficiently activated to split the azomethine bond by adding to phosphoric acid and thus liberate the FCG to start another cycle of oxidation. It is now accepted theory that creatine phosphate passes its energy on to ADP (adenosin diphosphate) to form ATP and the latter hands it over to the functional elements for work and growth. We then sharpened our Thesis by considering the exposed amine group of the adenine unit of ATP (which is activated by conjugation with a series of 4 sets of conjugated double bonds) as the group that condenses with the FCG of energy acceptance to pass the energy into the functioning elements.
One and the same FCG could perform both functions in rapidly alternating succession and thus account for the undulations estimated to run at some 30,000 per second when an impulse is conducted along a nerve fiber. We will discuss them as separate entities, however.
FCG blockage explained the ante-mortem coagulation of the blood in the parathyroid experiments. It explains the jelling of the blood in the early phase of an apoplectic stroke or coronary attack, for in both the administration of a Carbonyl group of high oxidation potential corrects the jelling of the blood so it flows freely and thus prevents the degeneration of the vessel wall that would lead to true thrombosis and infarction. Case histories will be given as examples, both of the block to energy production, as in coronary occlusion, and of the blockage in energy acceptance, as in exophthalmic goiter, even after the pathogen has integrated with the functional mechanisms concerned, the FCG systems of energy production, and the mechanisms of energy acceptance. When the normal tissue’s FCG has failed to dehydrogenate an amine pathogen, as when its O/R potential was too low, the firmly binding amine group must block FCG function. If because of anoxia the free radical formed in the pathogen, by its dehydrogenation at the hands of the FCG, has no oxygen to combine with it then adds to the activating double bond conjugated with the FCG and blocks its function. Therefore, the absence of adequate molecular oxygen is able to prevent the free radical, so formed, from becoming a peroxide free radical to be further burned. It would add to the activating ethylenic linkage of the FCG and thus block FCG function. Therefore, two circumstances are basic to the pathogenesis (a) the presence of a firmly binding amine structure and (b) the presence of anoxia; either, can block the FCG function to produce disease, or prevent the use of ATP for tissue cell development. The restoration of the growth process in hindered children of many classes and the reconstruction of tissues destroyed by cancer or by diabetic gangrene, demonstrate that restored FCG function can again use ATP not only for the primary cell functions, but for growth as well. Case histories will illustrate. The relation of the FCG to gene structure and function is thus opened for study. The destructive effects of irradiation on function and structure are another study in which we have collected important data, which must be reported some day in the interest of radiologists who have sustained injury, and of atom fission chemists who have been diseased through professional exposures.
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