The changes of metabolic activity of the skeletal muscle at various concentrations of caffeine were observed in connection with the mechanical change of the muscle.
1. At high concentrations of caffeine, mechanical change of the muscle was detected but the change of the oxygen consumption was not recognized. At low concentrations of caffeine, on the other hand, the quite opposite results were obtained, i. e. the oxygen consumption was increased but no mechanical change was observed.
2. In the K-depolarized muscle, 5mM caffeine increased the oxygen consumption of the muscle as in the case of the normal muscle.
3. Caffeine did not stimulate the respiration of the muscle homogenates and the muscle mitochondria.
4. Lactic acid content of caffeinized muscle increased with the increase of the concentrations of caffeine.
5. In the IAA-poisoned muscle, caffeine exhibited the increasing effect of the oxygen consumption as observed in the normal muscle.
6. The content of various phosphate compounds, CrP, ATP and ADP, decreased with the increase of the concentration of caffeine. On the other hand, inorganic phosphate (Pi) increased with the increase of the concentration of caffeine, in the range of concentration less than 5mM and decreased with the increase of the concentration of caffeine, in the range of concentration over 5mM.
Based on these results, it was suggested that, through a certain mechanism, various metabolic processes were stimulated by low concentrations of caffeine without any mechanical change.

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The correlations between electroencephalographic sleep level and some circulatory activities, i. e. the heart rate, blood pressure, pulse interval, velocity and amplitude of pulse wave during sleep were investigated on twenty healthy male students. The respiration, GSR, eye and body movement were recorded polygraphically. Most of these functions showed the distinct patterns in the lighter and deeper sleep stages, but there could not always be found a close parallelism with the depth of sleep especially in 1-5 stage, various functions showed particular patterns.

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In order to clarify the mechanism of E-C coupling process of the muscle, electrical and mechanical responses to the electrical stimulation and the relationship between their changes and the muscle weight were investigated in Ringer solution made hypertonic by the addition of glycerol or of the other several substances.
1. For about sixty minutes, for which the observation was made, features of resting and action potentials from single muscle fibres in 420mM glycerol Ringer solution were almost the same as those in normal Ringer solution.
2. The mechanical twitch responses of sartorius muscle immersed in glycerol Ringer solution were at first diminished and then restored with time elapsed. The most prominent restoration occurred in 420mM glycerol Ringer solution, and the maximum restored twitch tension of a single fibre, which attained to 50-60 minutes after exchanging the bathing solution for glycerol one, was 60-70 percent of that in normal Ringer solution.
3. In 420mM glycerol Ringer solution, the weight of sartorius muscle dropped to 74-82 percent of that in normal Ringer solution within a few minutes, and then the dropped value kept constant for about an hour.
4. The similar mechanical phenomenon was observed in rectus abdominis muscle but not in heart ventricle. It was also found in partially depolarized sartorius muscle stimulated by A. C. electric field.
5. The restoration of the mechanical twitch response did not occur in sartorius muscles under the condition of Ringer solutions made hypertonic by the addition of excess NaCl, mannitol, glucose, monoacetin and sucrose respectively, and the observable change was only a gradual diminution of mechanical twitch response. In the case of urea Ringer solution, however, the restoration appeared, though the grade was considerably less than that in glycerol.
6. From these results, the mechanism of the peculiar effect of glycerol was discussed in connection with the excitation-contraction coupling process of muscle.

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After isotonic hydrochloric acid was infused intravenously into 30 normal, 10 adrenalectomized and 5 DCA administered adrenalectomized dogs, changes of acid-base balance in the blood and urine were observed and the urinary acidification as well as of ammonia secretion was investigated.
The results obtained are summarized as follows:
1. Urinary output of titratable acidity and ammonia increased after the acid infusion and bore an inverse correlation with the blood pH. Acid urine formation was less remarkable in adrenalectomized dogs, while it was restored after the administration of DCA.
2. A positive correlation was found between plasma potassium concentration and urinary titratable acidity. The amount of titratable acidity is, however, lower in adrenalectomized dogs than normal dogs at the same plasma potassium concentration, while it is higher in DCA administered dogs.
3. It follows that the mineralcorticoid from the adrenal glands can play an importantant role in acid urine formation, probably by promoting an ion exchange mechanism of H⁺ for Na⁺ across the cell membrane of the renal tubule in acidosis. The fact that the acid urine can also be produced even in the adrenalectomized dog, though to a lesser extent, indicates that the urinary acidification can be initiated by the other factor than the mineralcorticoid. The direct effect of acidosis was suggested as the other factor, which may influence the H⁺ ion secretion mechanism of tubular cell in association with either K⁺ deficiency or pH decrease in the cells.
4. Urinary ammonia bears a clear inverse correlation with urinary pH, and an appreciable depression in urinary output of ammonia appeared in adrenalectomized dog, and this fact can be explained as due to the decrease of Na⁺-NH₄⁺ exchange in adrenalectomized dog. The predominance of the ion exchange theory over the capture-by-diffusion theory in mammals for the urinary ammonia excretion was discussed.
5. About the renal glutaminase and carbonic anhydrase activity, no difference could be found between normal and adrenalectomized dogs, suggesting no difference in the ability of production of acid and ammonia within the renal tubular cell in two kinds of animals.
6. It follows that a disturbance of Na⁺-H⁺ and Na⁺-NH₄⁺ ion exchange mechanism in the renal tubule in adrenalectomized dogs would result in a failure of adaptive increase of urinary output of acid and ammonia in acute acidosis.
7. It is confirmed with dog experiments that the increase of urinary ammonia in prolonged acidosis is due to an adaptive increase of renal glutaminase.

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1. Method was described for isolating and recording extracellularly a functionally single unit activity from the coccygeal lymph-heart of toad in spontaneous activity.
2. The single unit activity produced for an individual systole of the organ was composed of 3 to 5, most frequently, of 4 simple components, which were slow junctional potentials in nature, successively superposing on preceding ones, but without initiating any muscle impulse.
3. The component, the junctional potential which was able to be produced by stimulation to the root, was analo ous to the intracellular record obtained in the previous report, and also similar to s. j. p.in the skeletal muscle.
4. Conduction rate was determined on the nerve fibers which were responsible to the single unit activity. And at the level of the XIth ventral root, the rates ranged from 6 to 14m/sec which might fall in the boundary between those of the large-and small-nerve fibers in the skeletal muscle.
5. Mechanogram of the systoles of the organ was recorded with a calibrated mechano-transducer, simultaneously with the electrical activity. Each of the systoles showed a dome-like configuration of about 0.5sec and 0.3sec in duration at the levels of 10% and 50% of their maximum height. Complete relaxation took about 0.3sec after cessation of nerve volleys.
These findings were discussed especially in terms of the properties of the slow-muscle system in skeletal musculature in toad.

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The tendency to acidosis due to excess urinary Na loss over Cl after adrenalectomy has been studied in relation to the development of adrenal crisis in dogs. The lowering of the serum pCO₂ in the course of respiratory compensation for the bicarbonate wastage was found to play more important role than the derangement in Na and K metabolism. Increased susceptibility to acapnic central depression in the absence of glucocorticoids seemed to determine the course of the crisis, beginning with anorexia and ending in circulatory collapse. Infusion of NaHCO₃ but not NaCl solution could promptly ameliorated the anorexia in its early stage. The terminal bradycardia in the form of A-v block was found to be due to the result of autonomic unbalance rather than hyperkalemia and could be recovered by epinephrine or atropine without changes in the serum K level. It might be due to the sympathetic failure in the course of central depression and the animal succumbed to collapse before marked acidosis could appear.

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In order to clarify the mechanism of the excitation-contraction coupling of the cardiac muscle, the effect of caffeine on the cardiac ventricular strip of the frog was studied under various conditions and following results were obtained.
1. In normal Ringer solution, caffeine (5-50mM) did not cause the contracture of the strip.
Under the same condition, however, caffeine affected the automaticity and the contractility of the strip; a contractility increased at the low concentration (about 5-10mM of caffeine) and decreased at the high concentration (about 20-50mM), and the alternations of automaticity occurred arhythmia and arrest of pulsation. Even in the case of the arrest of pulsation, the mechanical responses to the electrical stimuli were observed.
2. The high concentration of caffeine (50mM) caused decrease of both resting potential and duration of plateau of the action potential, but these changes were recovered in the normal Ringer solution. This indicates that the effects of caffeine are perfectly reversible.
3. By the prolonged immersion in the high concentration of caffeine, the contraction by electrical stimuli was limited to a localized area.
4. One of the conditions for inducing caffeine-contracture is the deficiency of sodium in the bathing solution, that is, the contracture occurred in the Ringer solutions of which sodium was replaced by KCl, choline chloride or nonelectrolytes (sucrose, glucose and glycerine). The other condition indispensable for inducing the contracture was the existence of calcium which could be removed by the application of chelating agent. The treatment by Ca-free medium was not sufficient enough to remove the calcium from the cell.
5. The grade of the contracture was dependent on the concentration of calcium and sodium contained in the Ringer solution; at the constant concentration of sodium, the grade was higher in the higher concentration of calcium; at the constant concentration of calcium, the grade was lower in the higher concen tration of sodium.
From these results, the mechanism of the excitation-contraction coupling and the affected site by caffeine were discussed in comparison with the case of the skeletal muscle.

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As an approach to understanding of the peripheral effector mechanisms of the galvanic skin reflex (GSR), impedance changes were measured at the palm and dorsum of hand on 17 healthy male adults with special reference to COLE'S circuit. The measurement was conducted with sinusoidal current of nine different frequencies ranging from 30 to 10, 000c/s and with low frequency square pulses.
1. At each frequency of sinusoidal currents, resting impedance of the skin was measured with the result that impedance locus for each frequency was found to occur fairly well on a circular arc as was expected from the assumption that COLE'S circuit is suitable as equivalent to impedance of the skin.
2. By means of Lissajous' figures, changes in resistance, in reactance and in absolute value of impedance were measured at each frequency of the sinusoidal currents. It was found that resistance of the skin decreased at lower frequencies and increased at higher frequencies, whereas reactance always decreased irrespective of frequency. In spite of this variation in resistance change, the absolute value of impedance always decreased, although to a progressively lesser extent with increase in frequency.
3. On the basis of these experimental results and of the results obtained by analyzing the traces of the impedance loci during the GSR, it was suggested that impedance change of the skin during the GSR may be only due to decrease of the leakage resistance R₂ of COLE'S circuit.
4. In the experiment with square pulses, initial resistance, initial capacitance and residual resistance were measured from the polarization curves during the GSR. Residual resistance decreased markedly without any appreciable change either in initial resistance or in initial capacitance. These results are in agreement with those obtained by the use of sinusoidal currents.

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The effects of the sympathomimetic amines (adrenaline and noradrenaline) upon the transmembrane potential of both atrial and ventricular fibers of the toad were studied. Transmembrane potentials were recorded by glass-pipette microelectrode.
1. In the atrial fibers, these amines increased the resting potential at an early stage. An increase was also observed on the overshoot and duration of the action potential. At the same time a slowing of the terminal phase of depolarization and a slowing of the initial phase of repolarization was observed in some cases.
At a later stage, these changes were replaced by a marked shortening of the action potential duration especially after a longer exposure to higher concentrations of the amines. This shortening of the action potential duration at the later stage was occasionally followed by fibrillation or flutter. All these later effects were abolished by atropine. This suggests that a liberation of acetylcholine or some allied substance from the atrium in an amount sufficient to mask the effects of adrenaline occurs.
2. Similar changes were observed in the ventricular fiber as a result of the administration of sympathomimetic amines.
3. Premedication of the animal with reserpine sensitized both atrium and ventricle to the sympathominetic amines.
4. Acetylcholine and sympathominetic amines are antagonistic and counteract each other in their effect on the duration of the action potential.
5. The effect of adrenaline on the atrial membrane potential was not essentially altered by changing the cationic concentrations of the external fluid.
6. The mode of action of adrenaline on the membrane potential is discussed on the basis of the results obtained.

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