1. A structure (muscle fascicle) resembling a false-tendon was occasionally found (in 12 of 23 animals) in the right atrium of the monkey, Macaca irus, at a geographical location corespond, ing to the usual site of the specialized conduction system of the atrium, a subject that has long been studied by this author. This structure generated action potentials preceded by a slow diastolic depolarizations. The cells constituting this structure differed, both optic-microscopically and electron microscopically, from ordinary atrium muscle cells in that the cells were small in size, irregular in arrangement and with in nuclei, a histological feature that makes this structure appear more or less like nodal tissues. 2. Investigation of serial sections made to-wards too directions, that is, upward to the sinus node and downward to the A-V node from this structure, showed that this structure was in continuity with muscle bundles of similar nature towards both directions. 3. Investigation on the hearts of 62 rabbits by means of microelectrodes showed that, when a shift of pacemaker from the heed to the tail of the sinus node has been previously produced by the application of acetylcholine to the sinus node, section of the systema septoangularis post. resulted in a complete dissociation between sinus node and A-V node. 4. The location of the tip of microelectrode was verified my effecting electrophoretic migration of cobalt hydrochloride solution, both for the head of the sinus node (usual site of the pacemaker) and for the tail of the sinus node (site of a pacemaker after the application of acetylcholine).

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Atrial fibrillation was initiated in a large possibility by either vagal stimulation or epinephrine injection during vagal stimulation after infusions of 2 per cent sodium lactate, 2 per cent sodium bicarbonate and 1/10N sodium-2-phosphate in closed chest dogs. The incidence of atrial fibrillation produced from 40 to 120 minutes after infusion was more frequently than that of an immediate termination of the infusion. After infusions of these solutions, serum sodium and potassium concentration increased, but serum calcium concentration decreased. Occurrence of atrial fibrillation was observed in a few cases after infusions of 1.4 per cent and 0.9 per cent sodium chloride, and was not observed after infusion of 1/10N sodium-1-phosphate at all. After infusions of these solutions, the concentration of electrolytes in serum as mentioned above did not change.

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The diagnostic value of ventricular premature beats in myocardial infarction has been studied by several authors. The specific morphology which permits the diagnosis of infarction is generally considered to be QR pattern. The qR pattern, however, was included in this group of "infarction ventricular premature contraciron" by some authors In the presentstudy, theoccurrenceof QR and qR patterns in various leads of routine electrocardiograms was examined separately and their diagnostic significance was discussed.

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1) It has been revealed that glycine, threonine, and histidine have their own Tm. Experimentally an analysis is made of the titration curve of the aminoacids after loading of amino-acid-mixture and 1-histidine loading to patients with renal diseases and to normal subjects. A reabsorption ratio is decreased in renal disease cases in a range up to the load area of Tm. 2) An increase of loaded amounts of amino-acids resulted in a gentle continuous slope but never "shoulder" on the titration curve. This "shoulder" phenomenon observed on the glucose titration curve is considered to be due to the presence of the nephron population. It is therefore, not referable to aminoacids. Assuming that the transfer reaction proceeds as follows : A+B<ruluhar>AB<roarra6gt;B+A where A is transferred material B is carrier AB is complex, then, equation, K(x-y)(c-y)=y, can be introduced where x corresponds to loaded amount, c the number of carriers, y a transferred amount and K equilibrium constant. If K is of a finite value in the reaction of the first degree, one can not expect "shoulder" phenomenon in the titration curve. 3) A deformed titration curve in cases of diseased kidney suggests the presence of a decrease of c (carrier) and also of an apparent decrease of K. Although the decrease of K can be expected from transfer enzyme abnormalities in cases of congenital aminoaciduria, it is hard to expect its occurrence in non-specific renal lesions. 4) On the basis of the present data, a new classification is proposed of aminoaciduria. Renal aminoaciduria in a narrow sence is due to abnormalities of the transfer reaction system, manifested by a decrease of c (carrier) and K (equilibrium constant), characterized by a decrease of Tm and reabsorption ratio. In aminoaciduria of hepatic coma cases which has been, formerly grouped in overflow type, abnormalities are pointed out in the transfer reaction system as well as increase of plasma aminoacids. A new term of "overload amino aciduria" is proposed for cases with a filtered load below Tm. Phenylketonuria is considered to be a typical overload aminoaciduria.

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1) An introduction was made of a theoretical model in consideration of several factors involved in the structural specificity of nephron. A stoichiometric analysis of aminoacid transfer mechanism in tubular cells was tried by a mathematical treatment. Urinary amino-acid excretion was formulated as follows : ln <CAA>/<GFR>=A- B/V 2) appropriateness of an equation induced by a theoretical model was tested by observing changes of urinary aminoacid excretion due to changes of a minute urine volume and proven to be valid. The normal kidneys of dogs and human beings were put on mannitol and water diuresis and urinary aminoacid excretion rate was measured. Changes of urinary aminoacid may be expressed as In <CAA>/<GFR>-=ln a - B/V with a high statistical reliance. 3) A deformed histidine titration curve suggesting a decrease of equilibrium constant k of transfer reaction in the diseased kidney proved to be the same as that of the normal kidney following correction of some factors on the basis of the theoretical formula. Reduction in reabsorption ratio and reaction constant resulted from an increased urine volume per nephron. 4) In the aminoaciduria in a narrow sense e. g. Fanconi syndrome, evaluation of changes only in the active transfer system becomes possible by correcting other factors by inducing such a theoretical formula. It is believed that this formula can be used as the basis of in-vivo stoichiometric treatment of the transfer mechanism.

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1) Tubular transport of sulfonamide compound occurs in a bidirectional manner; that is, both unconjugated and acetylated sulfonamide compound are secreted in the proximal segment and reabsorbed in the distal segment of the kidneys. The site of sulfonamide compound secretion is approximately identical with that of PSP or PAH secretion and the site of reabsorption lies between the sites of Na reabsorption and K secretion. 2) It is suggested that sulfonamide compounds are actively secreted in the proximal segment, and that for distal reabsorption an active transport and a partly diffusion mechanism are involved.

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Spironolactone, a potent aldosterone-blocking agent, was administered to 34 subjects including 4 patients with primary aldosteronism, and changes in plasma renin activity and electrolytes were followed up. Plasma renin activity was found to elevate during the medication in all subjects except 4, who were suffering from primary aldosteronism. In the latter subjects there was no increase in the renin activity. A possibility was suggested with regard to the differential diagnosis of primary aldosteronism from other mimicking hypertensions using this spironolactone test.

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The metal chelating action of the S=0 part of sulfamyl part was assumed on the basis of studies of the electronic state of the sulfamyl part of thiazide diuretics because of its similarity to the phosp'nate part p of ATP. The diuretic activity and inhibitory effect of thiazide on carbonic anhydrase may be explained as resulting from Mg⁺+ and Zn⁺+ chelating. ROBLlN'S model explaining the inhibitory effect of the sulfamyl part on carbonic anhydrase activity did not seem adequate from the viewpoint of quantum-chemistry.

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I. Clinical Observations 1. The "IJ value, "JM value and "JM/"IJ ratio have been measured as the quantitative expression of ultralow-frequency displacement ballistocardiograms in 259 hypertensive pa-tients and in 124 healthy persons. 2. In cases with arterial hypertension including three cases of polycythemia rubra vera, were observed the ascending dominant waves with a remarkably small "IJ and a tall "JM. 3. In normal adults, "JM/ "IJ ratio was proved to be 2.2-2.3 in all ages, however, a tendency to decrease was observed in "IJ, and "JM values. 4. In experimental hypertension (induced by noradrenaline injection) too, there was seen a decrease of "IJ value and an increase of "JM/ "IJ ratio. Among the hypertensive cases with an exceptronally low "JM/"IJ ratio, a dilatation of the ascending aorta and aortic arch was detected in most cases. 5. The main factor increasing "JM/"IJ ratio was a decrease of "IJ, which was especially influenced by arteriosclerosis and by an increase of systolic blood pressure. 6. No definite correlation was noted, among ECG, serum cholesterol level and eye-ground findings. 7. An obvious positive correlation was observed between the "JM/"IJ ratio and the low-/ high-frequency component ratio in the harmonic analysis of the pulse waves. 8. On the ultralow frequency ballistocardiogram, was noticed a largezr headward deflection in displacement of the body in each heart beat. The damping of this displacement might be considered to be a precipitating factor of the cerebral vascular lesions. II. Model Experiments 1. An experimental ultralow-frequency ballistocardiograph was designed and constructed. The apparatus consisted of the hammock-shaped bed, weighing 1.2 Kg and the natural frequency of the system being 0.23 cps, the damping being 4.1 per cent of the critical value, when the bed was loaded with 8Kg weight. 2. In order to search for the component of displacement wave and factors influencing the waves, a hydraulic circulatory model, was constructed, consisting from a glass flask as the heart and a rubber tube as the aorta. 3. Displacement wave was proved to be influenced by cardiac force, features of the blood vessel wall and blood pressure etc., and an especially close relationship was noticed between the shape of displacement wave and the elasticity of the aorta. 4. The ascending aorta and the aortic arch were proved to be the very parts which affected the displacement curves.

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Much has been discussed on the significance of catecholamine in disease conditions. But its relation to the autonomic nervous system in the area of cardioangiology is extremely important, from the observation of sympathicotonic aspect of the nervous system in reference to cardiac failure. Studies on these relationship serve to contribute to further clarification of the pathophysiology of cardiac failure. Previously, the author had studied 239 cases of cardiac failure complicated from the acquired valvular diseases and hypertensives. Determination of the urinary catecholamine in 24 hour urine were made and obtained the following results. 1) In grade II-IV of cardiac failures, urinary excretion of adrenaline and noradrenaline was found to be increased above the normal. 2) Adrenaline and noradrenaline have in-creased in an order of I, II, III of cardiac failure grade and up to 111 grade which was the highest. On the contrary in grade IV, slight decrease was shown but still higher than the normal level. This urinary excretion pattern of catecholamine in cardiac failure has well been recognized in each case. 3) Increase of adrenaline showed with relatively steadly pace, while noradrenaline excretion ranged rather widely. 4) Degree of increase in adrenaline and noradrenaline was due to severity of the disease rather than primary disease which complicated the failing heart. 5) The excretion ratio of adrenaline/aoradrenaline increased in degree with the progress of cardiac failure I, II, III, but in grade IV the value was below the normal. 6) The stage ofsympathico-adrenal activity as indicated by the increased urinary cate-cholamine in cardiac failure is presumably result of the regulatory mechanism. Hence, it is assumed that increased urinary catecholamine in cardiac failure may be advantageous for cardiac failure to improve, as previously re-ported. (The Journal of Japanese Society of Internal Medicine 53 : 413, 1964). Present studies were made (1) to make clear the pathophysiological significance of the sympathico-adrenal activity in cardiac failure by rapid digitalization on the patients suffering from acquired valvular heart diseases and of hypertension, and by observing the urinary excretion of active catechols referring to the clinical features with its relation to time before during and after rapid digitalization treatment. (2) To observe urinary excretion of active catechols with pilocarpine administration and upon response of the sympathetic nerve center in the failing heart. (3) To pursue the effect of decreased syrnpathico-adrenal activity on the cardiac failure, and by estimating active urinary catechols upon the administration of reserpine.

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Much has been discussed on the significance of catecholamine in disease conditions. But its relation to the autonomic nervous system in the area of cardioangiology is extremely important, from the observation of sympathicotonic aspect of the nervous system in reference to cardiac failure. Studies on these relationship serve to contribute to further clarification of the pathophysiology of cardiac failure. Previously, the author had studied 239 cases of cardiac failure complicated from the acquired valvular diseases and hypertensives. Determination of the urinary catecholamine in 24 hour urine were made and obtained the following results. 1) In grade II-IV of cardiac failures, urinary excretion of adrenaline and noradrenaline was found to be increased above the normal. 2) Adrenaline and noradrenaline have in-creased in an order of I, II, III of cardiac failure grade and up to 111 grade which was the highest. On the contrary in grade IV, slight decrease was shown but still higher than the normal level. This urinary excretion pattern of catecholamine in cardiac failure has well been recognized in each case. 3) Increase of adrenaline showed with relatively steadly pace, while noradrenaline excretion ranged rather widely. 4) Degree of increase in adrenaline and noradrenaline was due to severity of the disease rather than primary disease which complicated the failing heart. 5) The excretion ratio of adrenaline/aoradrenaline increased in degree with the progress of cardiac failure I, II, III, but in grade IV the value was below the normal. 6) The stage ofsympathico-adrenal activity as indicated by the increased urinary cate-cholamine in cardiac failure is presumably result of the regulatory mechanism. Hence, it is assumed that increased urinary catecholamine in cardiac failure may be advantageous for cardiac failure to improve, as previously re-ported. (The Journal of Japanese Society of Internal Medicine 53 : 413, 1964). Present studies were made (1) to make clear the pathophysiological significance of the sympathico-adrenal activity in cardiac failure by rapid digitalization on the patients suffering from acquired valvular heart diseases and of hypertension, and by observing the urinary excretion of active catechols referring to the clinical features with its relation to time before during and after rapid digitalization treatment. (2) To observe urinary excretion of active catechols with pilocarpine administration and upon response of the sympathetic nerve center in the failing heart. (3) To pursue the effect of decreased syrnpathico-adrenal activity on the cardiac failure, and by estimating active urinary catechols upon the administration of reserpine.

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Previously N.KATUNUMA et al. discovered that GOT from pig liver consist of two types of isozyme, the one being localized in cell supernatant fraction (GOTs) and the other in mitochondria (GOTM). Subsequently they succeeded in purifying the isozyme to almost single protein. Using the technique of column chromatographic separation, the author could elucidate the mechanism of the leakage of the GOT-isozvme from the heart muscles into serum in the case of experimental myocardial infarction. Method s In dogs, experimental myocardial infarction was produced by ligation of the circumflex branch of the left coronarv arterv, and a few to several dogs were killed at a certain period of time after the occlusion (24 hr, 2 day, 3 day, 4 day, 5 day, 7 day, 10 day, 14 day after operation) and the direct ECG was recorded respectively, before slaughter. Then, the removed heart was separated into the infarcted and non-infarcted portions, and the GOT ac-tivity in the heart muscles obtained from each portion was measured. In order to separate the GOT-isozyrne quantitatively, HUZlNO-KATUNUMA'S method was used, and the GOT activity was expressed by a modified method of FRIEDMANN-HAUGEN. Results 1. GOT-isozyme in heart muscles. 1) The ratio of the total activity of GOTS to that of GOTM in normal heart muscles was about 4 to 1 on the average of 2 dogs. 2) At 24 hours after the occlusion, the ratio of the total activitv of GOTS to that of GOTM in the non-infarcted portion was about 4 to 1 on the average of 5 dogs, while in the infarcted portion, it was about 1.2 to 1. Namely, the total activity of GOTS in the infarcted portion was decreased to about 2S per cent of that in the non-infarcted portion. On the contrary, any significant change of the total activitv of GOT_M in the infarcted portion could not be observed compared with that of the non-infarcted portion. 3) At 2 days, 3 clays and 4 clays after the occlusion in 2 dogs respectively, no change of the total activity of GOT_M could be observed between the infarcted portion and non-infarctecl portlon, just like at 24 hours after the occlusion. As for the total activity of GOTs, the rates of decrease were 71.8 and 72.1 per cent after 2 days, 74.8 and 77.7 per cent after 3 days, 73.9 and 77.5 per cent after 4 days respectively in the infarcted portion compared with that in the non-infarcted portion.

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