It was shown that although the first inoculation of even a small amount of endotoxin during intravenous epinephrine infusion precipitates shock, by inhibiting the epinephrine removing capacity, after repeated endotoxin pretreatment a marked resistance to epinephrine infusion can be induced by virtue of a pronounced adaptation of the epinephrine removing capacity. This enhancement of the epinephrine removing capacity in the endotoxin-tolerant state was observed even in the absence of glucocorticoid which is also able to induce it. It was discussed that some of the effects of glucocorticoid can be realized in the adaptation to endotoxin conditioning. This would shed a new light upon the problem of cross-resistance of endotoxin-tolerant animals to other stresses not concerned with bacterial endotoxin.

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1. Reflex inhibition of cold shivering due to mechanical pressure applied on the face on the rabbit and its primary afferent pathway in the central nervous system was studied to clarify the mechanism of the “skin pressure reflex.”
2. Mechanical pressure on the eye-ball and the ear-root was greatly effective in inhibiting cold shivering.
3. The spinal trigeminal tract is the afferent pathway of the reflex inhibition of shivering by pressure on the face, that was proved by the tractotomy of the trigeminal nerve in the spinal cord.
4. The trigeminal fibers entering directly to the main sensory nucleus is not associated with the reflex inhibition. Small fibers of the spinal trigeminal tract, considered as GII or GIII fibers from the result parameter of electrical stimulation of the tract, might play an important role in conducting the impulses evoked by pressure applied to the face.
5. Phylogenetical aspects of the spinal cord and the anatomical, functional characteristics of the peripheral nerve were discussed in relation to the mechanism of the “skin pressure reflex.”

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1. Investigations on the inhibitory neuromuscular junction of crayfish stretch receptor muscles were performed electrophysiologically and electron microscopically.
2. Fast receptor muscles responded to direct stimulation with a transient depolarization which exhibited the property of a propagated action potential, but did not show any overshoot. On the other hand, slow muscles did not generate an action potential but showed excitatory junction potentials of 10-30mV in amplitude. EJPs of fast receptor muscles were summated by repetitive stimulation until all-or-nothing spikes were generated.
3. When a nerve bundle was carefully isolated and one of the isolated filaments were stimulated, inhibitory junction potentials could be obtained from fast stretch receptor muscles by the microelectrode inserted near the receptor neuron. They had a reversal potential approximately at-60mV. Inhibitory junction potentials completely inhibited excitatory junction potentials and spikes when inhibitory nerves were stimulated at high frequency of 100c/s for several seconds.
4. Application of GABA of 10^-4-10^-5M showed similar effects to stimulation of inhibitory nerves. It's effect was due to the increase of postsynaptic membrane conductance.
5. Two different types of synapses were identified electron microscopically at fast stretch receptor muscles. The one contained spherical synaptic vesicles, the other ellipsoidal ones. The latter was observed within the limit of the vicinity of the neuron soma. From UCHIZONO'S (1965, 1966) previous studies and the present electrophysiological experiments, it was concluded that the latter was the terminal of inhibitory neuromuscular junctions.

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In an attempt to know the role of serotonin in fatty acid metabolism of brown adipose tissue, lipolytic action in vitro of this amine was examined in the interscapular brown as well as epididymal and mesenteric white adipose tissues of the rat. It was found that the addition of serotonin in a final concentration of 5×10^-4M caused a small, though signifcatnt, increment in FFA release from mesenteric adipose tissue, whereas in brown and epididymal adipose tissues serotonin had no effect. This pattern of serotonin effect was not affected at all by the presence of safrazine, a potent monoamine oxidase inhibitor.
However, in the presence of theophylline which blocks phosphodiesterase and prevents the degradation of cyclic AMP, a marked increase of FFA release due to serotonin was observed in all adipose tissues studied, the response being the greatest in brown adipose tissue. It is noteworthy that this action of serotonin was dose-dependent in the dosage range from 5×10^-7 to 5×10^-5 M with a maximum response at the latter concentration. Furthermore, the increment of FFA release by serotonin was found to be accompanied by a similar increase in oxygen consumption in brown adipose tissue. It is inferred that serotonin may participate in the thermogenesis through acceleration of a process involving lipolysis and reesterification cycle in brown adipose tissue.

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Brain stem lesions and stimulation effects upon prefrontal electrical activity in relation to limbic evoked potentials and after-discharges were studied in 20 squirrel monkeys. The studies were performed under phencyclidine hydrochloride (Sernylan) anesthesia.
After-discharges elicited from the amygdala and hippocampus propagated to the prefrontal cortex following the lesion in the field H of Forel, whereas the septal stimulation elicited a self-sustained prefrontal after-discharge and a limbic after-discharge. Evoked potentials in the prefrontal cortex with the stimulation of the septum, amygdala, and hippocampus were attenuated by the conditioning stimuli in the field H of Forel.
It was concluded that the lesion in the field H of Forel increased the excitability of prefrontal cortex to limbic stimulation and after-discharges.

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Cold pressor response was examined on several groups of sub jects, including 2 groups of the Ainu in Hokkaido.
1. The rise of systolic blood pressure in response to cold water immersion of a hand was more pronounced in sub jects who were born on the main island, as compared with that in those born on Hokkaido.
2. The cold pressor response of the Ainu was considerably great in comparison with that of the Japanese, although the Ainu and hybrids of Ainu-breed were self-confident of their strong resistance to cold. Accordingly, existence of ethnic difference in the response was suggested.
3. Fish factory workers as well as fishermen showed only small rise of the blood pressure in response to local cooling. The response of farmers and nurses in the coldest districts in Hokkaido was greater than that of the above fish port groups, and Japanese and Ainu-hybrid farmers in warmer districts showed also high response in the winter.
4. In the Ainu the rise of blood pressure in summer was higher than in winter. Seasonal changes in the response were negligible in hospital nurses. These findings, together with the categories 1 and 3, were interpreted possibly due to their living conditions and experiences to cold.
5. Repeated immersions of the same hand in cold water caused a diminution of blood pressure rise.
6. A highly significant correlation was demonstrated between the cold pressor response and pressor effect of norepinephrine.
7. The cold pressor response was diminished after treatment with hexamethonium bromide.
8. Cold water immersion of a hand caused a rapid transient increase in the plasma level of FFA. The increase in plasma FFA was less marked in the Ainu, as compared with the changes in the Japanese.
9. The rise of blood pressure in response to local cooling was not paralleled by the increase in plasma FFA level.

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1. A plasminogen activator was demonstrated in mammalian bile by the unheated calcium-rich fibrin plate and heated fibrin plate tests.
2. Active fraction, which was free of bile salts, was obtained from bile after gel filtration using Sephadex G-75. Some enzymatic activities of this fraction, which we termed bilokinase (BK), were studied using fibrin, casein and TAMe as substrates.
3. Our results suggest that bilokinase itself is a protease capable of caseinolysis, but only slight fibrinolysis and no TAMe hydrolysis. The activating activity of bilokinase is demonstrable by fibrinolysis and caseinolysis, but not by TAMe hydrolysis. Such activating activity is inhibited by trans-AMCHA, and easily inactivated by heating or pH manipulation.

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Employing a Nembutal anesthesia, a cat was decerebrated, a quantitative study was performed on the distribution and overlapping of the evoked potentials obtained from the utricular, trigeminal and radial nerve stimulation in the cerebellar anterior lobe.
1. The waveform of evoked potentials obtained from the utricular, trigeminal nerve stimulation were the same in nature as that of radial nerve stimulation, i.e., the deflection consisted of the first slow positive, the second marked fast positive and the last slow negative deflection. The distribution of the utricular evoked potentials was localized at the ipsilateral margin of the anterior lobe but the trigeminal nerve representation spread along the folium in the cerebellar anterior lobe, contrasted with the longitudinal arrangement of the radial nerve representation.
2. The recovery process of the evoked potentials obtained by double shock stimulation of each nerve showed a smooth identical curve which recovered almost 100% by one sec, 85% by 0.3 sec. and 50% by 0.1 sec. but the second stimulation was invalid by 0.03 sec.
3. The recovery process of evoked potentials obtained by different nerve stimulation in six group of combinations showed the wavy periodical fluctuation which seemed to be due to the reverberating circuit of the cerebellum. This recovery ratio had a linear relationship to the negative components of the preceding potentials whose size was parallel to the synchronous firing of the Purkinje cells.
4. The mode of overlapping of activity due to occlusion of representations elicited by simultaneous double shock stimulation to different nerves, was different at the six points of the lateral portion of the cerebellar anterior lobe. It was demonstrated that the overlapping ratio of the simultaneous triple shocks could be anticipated from the result of overlapping in double shock stimulation.
5. It was found that the reduction ratio of the potentials, obtained from simultaneous stimulation of the different nerves, was not proportional to the amplitude of individual evoked potentials, but the ratio of the unaffected area of the major representation in double shock stimulation to the original extent of the representation, i.e., the residual ratio was a function of the potential height in a hyperbolic fashion.
6. The varying ratio of occlusion with lapse of time was followed and it was observed that the extent of the occluded area fluctuated with waxing and waning phases when activity produced from different kinds of nerve inputs interfered each other.

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Plasma lipid profiles in the winter were studied in 128 male subjects. They were Japanese sub jects born on the main island, those born on Hokkaido, and Ainu.
Appreciable differences were not detected among these three groups in the concentrations of total lipids, triglycerides, phospholipids, total and free cholesterol, and esterifled fatty acids in the plasma, although average values of total cholesterol and phospholipids were considerably low, as compared with values reported by American or European investigators.
Highly significant differences were observed in the plasma levels of FFA; the lowest values were obtained in the Ainu who were considered to be well adapted to cold, while the highest in sub jects born on the main island and not adapted to cold.
The results suggest that FFA mobilization is related in some way to the thermoregulation in the cold and the development of cold acclimatization.

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Non-anesthetized ovariectomized cats were employed for recording hypothalamic unit activity. The discharge pattern of the neurones which responded to blood LH or oxytocin were analyzed from statistical view-point.
1. The pulse train of neuronal activity was analyzed into discharge interval histogram. In addition the statistical dependency between mean discharge interval and standard deviation was calculated. In three fourths of the hypothalamic neurones the discharge activity showed exponential or gamma type distribution of discharge interval and the rest showed either normal, Poisson or unclassified distribution. In the control condition the coefficient of regression was between 0.9 and 1.4 and the linearity was good. Although no essential difference existed in the distribution of inter-spike interval between estrus and anestrus, an increase in the discharge rate was observed in anterior hypothalamic neurones and a decrease in LH neurones.
2. Both at estrus and anestrus LH administration caused mean discharge interval of the anterior hypothalamic neurones to decrease and of the VMH neurones to increase. The change in discharge interval by LH at anestrus was accompanied by an increase in standard deviation and the same mean-SD relationship was kept as before administration.
On the other hand LH administration at estrus resulted in deviation of mean-SD relation from the regression line of the control condition. The latter type of change could be observed in a few neurones of unclassified distribution in the VMH and AHA.
3. By oxytocin administration at anestrus the discharge rate of AHA and LHA neurones increased and of VMH neurones decreased. On the contrary at estrus oxytocin injection caused discharge rate of lateral hypothalamic neurones to decrease and of ventromedial hypothalamic neurones to increase. In the majority of these cases, the change could be plotted on an extension of mean-SD regression line obtained before administration. But there were a few neurones which showed a deviation downward from the control regression line. This type of change was observed only in neurones of unclassified distribution.
Discussion was made on the mechanisms underlying the changes in hypothalamic neuronal activity induced by administration of LH and oxytocin.

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The effects of negative pressure to the lower body (LBNP) which can well simulate the effects of positive acceleration on the cerebral blood flow and temperature were studied in 24 unanesthetized rabbits. Cerebral blood flow measured by the doubled heated thermoelectric flow probes increased during the application of lesser LBNP (-10-20 mm Hg). The increase of the flow was especially prominent in the animals not repeatedly exposed to greater negative pressure, and indicated the participation of some intrinsic regulatory mechanisms of increasing blood flow against the diminution of carotid arterial blood pressure. Cardiac acceleration with no change in brain temperature was also a characteristic feature under exposure to lesser LBNP.
When the animals were subjected to greater stress of LBNP (-50-80 mm Hg), cerebral blood flow decreased with rather complicated changes in brain temperature. Cardiac acceleration progressed, but in some cases a relative bradycardia appeared by the end of the 1 minute of application. With the release of LBNP, cerebral blood flow increased, but the increase was not prominent, despite of a marked overshoot of carotid arterial pressure.
A marked bradycardia with irregular cardiac rhythm, which might be a sign of cardiac decompensation developed by repeated exposures to greater LBNP. Cerebral blood flow decreased markedly under exposures to LBNP after which it increased profoundly. Brain temperature fell approximately by 0.3°C. after the release of negative pressure. The increase of cerebral blood flow after the release of negative pressure is probably due to passive dilatation of cerebral vessels after direct inhibition of neurogenic casoconstrictor center in which developed some irreversible functional destruction by the repeated exposure to greater LBNP.
Brain temperature was rather closely but inversely related to the changes in cerebral blood flow in many cases. It seems, therefore, very likely that in such circumstances the cerebral tissues may be cooled by the arterial blood passing through the vascular trees of the brain, and in this way this investigation could throw a little light on the central mechanism of temperature regulation. The mechanism of the epileptiform seizures frequently observed during and after exposures to positive acceleration may be interpreted by the changes in cerebral hemodynamics as described in this paper.

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