1) Environmental factors on surface of earth and moon are very different: almost no atmosphere, no barometric pressure, no oxygen, neither water nor moisture, perhaps CO, CO₂, and H₂SO₄ (volcanic). Surface temperature changing from 390 to -160°C, radiation much more intensive than on earth (unfiltered) und surpassing limits of earth's spectrum on both sides.
2) Many vitally important functions will be impaired: respiration, metabolism, blood circulation, absence of all accoustic influences (deaf-muteness), all movements are very excessive, uncontrollable, atactic. Danger of massive respiratory and intestinal haemorrhages.
3) Residence (entering and landing) of unprotected men on moon will be fatal. The following preliminary investigations are indispensable:
a) Climatic-chamber tests with all sorts of living beings, subjecting them to conditions equal or similar to those on moon so as to state maxima and minima of man's tolerance.
b) Collecting data and samples from moon's surface to be examined in our laboratories.
c) Placing several kinds of mammals on moon-surface, observing them living and, perhaps, dying (necropsy).
d) First landing of man: to be equipped with
aa) flexible rubber-tubing for air, water, and food from the flying machine
bb) diving-bell suit with all its accessories.
Both these experiments dangerous. Hard manual labour impossible, therefore no agriculture and mining.

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This paper summarizes the studies concerned with the effects of high body temperature induced by thermal bath, hot environment and artificial fever in humans on water and electrolyte metabolism, which is an essential regulatory mechanism in the living body for the maintenance of its internal environment, i. e. homeostasis. Also, some related changes in circulatory and adrenocortical functions were discussed.
I. Thermal bath (plain water and hot spring)
15 healthy men and experimental animals were studied and series of comparative measurements before and after each bathing for 10 minutes at temperature from 40 to 43°C have been performed. A rise in mouth temperature of 1.8°C was observed.
1) Immediately after bathing no changes were observed in body weight and total body water (TBW). This suggests, that water loss (sweat secretion and urine) probably equals percutaneous absorption of water.
2) Extracellular fluid (ECF) and plasma volume (PV) increased by 2.0% and 5.5% respectively; henmtocrit was lowered. while total blood water as well as plasma water both increased and blood cell water decreased. This result was inferred to a shift of water from intra- to extracellular fluid.
3) The minute volume of urine voided after bathing showed a transient increase, whereas it immediately decreased thereafter and became also less than at the pre-bathing level.
4) Plasma Na concentration was lowered after bathing, while K and Cl concentration remained unchanged. Na content of the blood corpuscle showed a rise, K content was lowered and Na/K ratio was increased.
5) Reabsorption of Na, Cl as well as excretion of K in the urine increased slightly after bathing. The same tendency was also observed in bathing after an intravenous hypertonic sodium chloride solution had been previously loaded.
6) As for tissue electrolytes Na increased after bathing, while K decreased in the skeletal muscle of rats.
7) The permeability of Na²⁴ across the capillary wall increased during and immediately after bathing, in dogs.
8) The increases in adrenocortical activity were observed during bathing, in humans, and rats, and these are considered to play a major role in the whole processes of general adaptation of the living organism to bathing. Also the antidiuretic substance decreased during bathing.
II. Hot environment
Water and electrolyte metabolism was studied by the same methods used in experiments of thermal baths, in 11 patients without signs of edema immediately prior to entering a hot room for 1 hour (40°C, relative humidity 50-58%), and 60 minutes after leaving the room. The rise in body temperature was 0.5-1.4°C.
1) Hemodilution was found, when patients' sweat secretion was not abundant, after the first 30 minutes of heat exposure. Thereafter profound sweating started. At that time TBW, ECF slightly increased, plasma and whole blood water also increased, and blood cell water and hematocrit decreased. Immediately after leaving the room dehydration was found. When perspiration was profound, the early hemodilution was absent and hemoconcentration supervenes as a result of dehydration. The minute volume of urine gradually decreased after the entrance.
2) No changes in plasma Na, K and Cl concentrations were observed. Electrolyte clearances, especially Na and Cl clearances fell gradually. Decreases in excretion of Na, Cl in urine was more pronounced than that of K, and these were not paralleled to GFR but to urine volume. Reabsorption of Na, Cl and water increased probably because of early sweating.
3) 17KS in urine increased after 60 minutes' entrance in a hot room.
III. Artificial fever
Water and electrolyte metabolism during pyrogen (T. T. G.)-induced fever was observed in humans (3 healthy men and 4 patients without edema). The rise in body temperature of 2.5-3.0°C was obtained.
1) ECF, TBW, ICF and PV increased slightly in the highest body temperature stage; and hemat

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The author selected such alpine heights above sea level as 3, 000 meters (Hodaka Dake), 2, 800 meters (Norikura Dake) and 2, 000 meters (Ena San) and conducted studies, with rabbits and healthy adults as the subjects, as to what type of in vivo reaction such environmental conditions will bring about. Kinetic observations were made in conjunction with the progress of blood pressure, pulse rate, protective colloids in urine, hepatic function, reticuloendothelial system, number and property of erythrocytes, bone marrow picture, oxygen saturation percent, serum iron, etc. and the following results were obtained.
1) In high altitudes, there was a rise in both systolic blood pressure and diastolic one, but it was more conspicuous in the latter. Also, increase in the pulse rate was noted in all cases during the stay in the mountains, and the rate was the highest on the second and third day of mountain-climbing with a gradual decline thereafter, but a return to normal was seen soon after descent from the mountains. Variations of blood pressure and pulse rate in line with postural alterations were generally stronger in high altitudes as compared with level grounds and the duration for it was longer, leading to slow restoration.
2) In high altitudes, a transient increase of protective colloids in urine, owing to sojourn in mountains, was observed with the manifestation of abnormal values with increasing frequency. This increase of protective colloids in urine was reduced through the administration of a sensitive pigment, Platonin. By means of the addition of physical exercises and environmental changes due to mountain-climbing, the average urinary amount of protective colloids in 16 subjects became about twice as much as that prior to the climbing.
3) The summation of the results on the serum icteric index, discharge of urobilinogen in urine, pigment-discharging function by bromsulphalein test, serum total protein and electrophoretic analysis was, that under the alpine environment, transient hepatic dysfunction was observed, even though to a slight degree, at the outset of transference to the high altitude.
4) As regards the function of the reticuloendothelial system, observations through the Kongorot coefficient revealed a slight hypofunction at high altitudes and temporary slight-hyperfunction in parallel with the descent from mountains, followed by a gradual restoration to the premountaineering conditions.
5) Splenectomy prior to transference to high altitudes did not exhibit a double-peak rise in the number of erythrocytes usually seen at the time of transference to the altitudes, but showed a transitory single-peak rise with the highest values around the 4th day of mountaineering. Moreover, in splenectomized cases there was vigorous production of erythrocytes in the bone marrow immediately after mountaineering.
6) The oxygen saturation percent in the blood decreases along with the alpine environment and the decrease is considered to be compensated by increase of the hemoglobin and hematocrit values as well as of the diameter of erythrocytes, etc. The decrease of oxygen saturation is continued until the 3rd to 4th day of descent from the mountains.
7) There is a striking reduction of serum iron directly after mountaineering. Afterwards, a slight rise in the amount is perceived during the stay in the mountains but being below the value before climbing. This tendency is recognized after the descent from mountains as well, returning to the premountaineering value in about 3 weeks after the descent.

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Experimental studies were performed on the role of the central nervous system in thermoregulatory function from the standpoint of fever reaction. At first observation was made on the changes of the fever reaction following heat puncture caused by the modification of various regulatory systems. Next the thermoregulatory role of the amygdaloid nucleus in the cerebral limbic system was investigated by means of heat puncture. In addition, the temperature and electroencephalogram of the hypothalamus and amygdaloid nucleus after the administration of pyrogen, adrenaline, and noradrenaline were observed in the course of time. As a result the following findings were obtained.
1) In the case of heat puncture immediately after section of the bilateral splanchnic nerves, the reaction of body temperature rise was maintained comparatively well, but the duration of it was shortened, presenting an evidently different course compared with the normal case. However, one week after the operation the change of body temperature was almost the same as in the normal case.
2) The rise of body temperature following heat puncture was not observed after pretreatment with chlorpromazine.
3) The body temperature rise following heat puncture was not observed 24 hours after the bilateral adrenalectomy, however, administration of cortisone restored body temperature similar to that of the normal case.
4) In liver disorder caused by carbon tetrachloride, heat puncture produced body temperature rise in cases to which small amount of carbon tetrachloride was administered, but did not in cases to which a greater amount was administered.
5) Many cases manifested a fall of body temperature immediately after the puncture at the lateral amygdaloid nucleus, resulting in a gradual rise of body temperature.
6) In many cases the puncture at the anterior amygdaloid nucleus produced a slight rise of body temperature.
7) In many cases the puncture at the medial amygdaloid nucleus produced a slight rise of body temperature.
8) The brain temperature change in various portions, anterior and posterior hypothalamus and amygdaloid nucleus by the administration of pyrogen (T. T. G.), adrenalin and noradrenalin showed a slight difference in the grade of change by its location. But the direct relationship between these local temperatures and their electroencephalograms had not been recognized.
9) The electroencephalogram of the anterior and posterior hypothalamus and amygdaloid nucleus in fever by administration of pyrogen (T. T. G.) showed, that high-frequency low-voltage waves became dominant 30sec. after injection, and the tendency kept on 10-15min., and thereafter restored gradually to the level of pre-administration. But in the temperature rising period, and in its previous period the tendency of high-frequency low voltage waves was observed again periodically and in the body temperature descending period a tendency towards slow waves was observed.
10) During the period from immediately to 5-7 minutes after the administration of adrenaline in a small dose (0.005mg/kg) a marked high-frequency low-voltage reaction was observed in the electroencephalogram of the hypothalamus and amygdaloid nucleus.
11) Administration of adrenaline of a medium dose (0.1mg/kg) gave rise to a marked rise of body temperature. The electroencephalogram of the hypothalamus and amygdaloid nucleus showed high frequency during the period from immediately to 3 minutes after the administration, recovered gradually to the normal activity level, and manifested a tendency to high frequency again at the hyperthermic stage.
12) Administration of adrenalin in a large dose (0.5mg/kg) gave a slight fall of body temperature, and E. E. G. of hypothalamus and amygdaloid nucleus showed a tendency towards low frequequency high voltage, slow waves.
13) Following the administration of noradrenaline almost a similar tendency as in the case of adrenaline was observed, although in a mediu

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Effects of hotspring bathing on various circulatory functions in man ware studied at the Kombugawa Onsen (muriated alkaline spring), Kombu, Hokkaido.
A) Effects of the single bathing on the circulatory functions.
1) Pulse rate showed a diphasic change, namely, it increased immediately after bathing, decreased below the prebathing rate 60 minutes later and then gradually rose but did not reach the initial rate even 120 minutes later.
2) i) Systolic pressure decreased immediately to 60 minutes after bathing and then tended to return but not reached the prebathing level even 120 minutes later.
ii) Diastolic pressure showed the lowest level immediately after bathing and returned to its previous level within 90-120 minutes.
iii) Pulse pressure took the lowest value 30 minutes later and showed the prebathing value within 90-120 minutes.
iv) The higher the initial systolic pressure, the more marked was the systolic pressure reduction after bathing.
v) There was no significant change in effects on systolic pressures after bathing between 38°C bath for 20 minutes and 41°C bath for 10 minutes.
3) Arm-to-pharyngeal circulation time was shortened immediately after bathing.
4) RR interval of ECG was definitely shortened 5 minutes after bathing and gradually returned thereafter. No significant change in configuration of complexes, PQ, QT interval and QT ratio occurred.
5) Amplitudes of systolic complexes HI, IJ, JK in ballistocardiogram increased by 30% soon after bathing and decreased by 10% 15 minutes later.
L, M and N waves increased or became more definite immediately to 10 minutes after bathing in half of the cases.
6) Cardiac output slightly increased 10 to 15 minutes after bathing.
7) i) Pulse wave conduction time (the time from the beginning of Q in ECG to the beginning of upstroke in the plethysmogram) was not influenced by bathing.
ii) Crest time of plethysmogram tended to slightly shorten immediately after bathing, returned in 30 minutes and lengthened 120 minutes later.
iii) The upstroke gradient of the pulse wave markedly increased immediately after bathing and returned 120 minutes later.
iv) The amplitudes of pulse wave increased markedly soon after, then gradually reduced but was remarkedly higher even 120 minutes later.
B) Effects of the serial bathing on pulse rate and blood pressure.
1) No change in pulse rate was noticed.
2) i) Systolic pressure, diastolic pressure and pulse pressure decreased on the 2nd day and kept to a lower value during the course of bathings.
ii) The higher the prebathing blood pressure, the more marked the degree of blood pressure reduction.
iii) There was a significant correlation between the maximal systolic pressure reductions after single bathing and during serial bathings.

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Improving the mechanical switch converting direct current amplifier, the author made the particularly high sensitive high speed recording thermoelectric thermometer suitable to perform the investigation in the field of research on the body temperature regulation, especially on response of its mechanism, such as a low level information recorded in the form of small wave of temperature that operated by the acting fine tissue construction of the body.
Utilizing this instrument, the author made a study of the wave components of the fluctuation in the temperature recorded from the various parts of the body, and the fluctuation on the differential thermograms between them. This experiment was done by rabbits in various conditions, such as being normal and healthy, being given several drugs, or being affected by fever.
1. Several series of waves are observed in the every record taken from various parts of the body (skin, subcutan tissue, vein, muscle, liver, rectum, hypothalamus, etc.) indicating their inherrent property in them. Most of them belonged to the series whose frequency is approximately 3-0.5r.p.m. and also the slower ones are observed, which was superposed frequently on the former ones.
2. As the result of injection of adrenaline, the frequency of the wave was increased, and its amplitude was decreased, and sometimes the wave had a tendency to disappear, but about 20 minutes later, it appeared again.
Injection of noradrenaline showed the same tendency as above. However, chlorpromazine indicated the opposite tendency, that is, the frequency was decreased, amplitude also decreased and pulsewide enlarged. A large dose of chlorpromazine caused the wave disappear.
Injection of atropin caused only slight change in this wave.
3. Similar effect with that of adrenaline was observed on T. T. G. (which is polysaccharide fraction extracted from pseudomonus fluorescence).
4. There were remarkable fluctuations in the records of the earlobe venous blood temperature.
Differential thermogram between venous blood and its irrigated tissue of the earlobe indicated that the venous blood was warmer than its irrigated tissue, and the existence of the similar fluctuation described above was shown. These wave forms were complicated, but it is very interesting to analyse this changing mechanism or controlling process.
5. Effect of adrenaline, noradrenaline or chlorpromazine on differential thermogram between the earlobe and the rectum was measured, and as the result the character of stepwise phase was noticed there.
6. Result of injection of adrenaline, after giving a large dose of chlorpromazine, showed no effect on the temperature difference between the earlobe and rectum, while injection of either noradrenaline or T. T. G. indicated clear but slight increase of the temperature difference.
7. In every differential thermogram between the liver and the rectum, temperature of liver was somewhat higher than that of rectum, and difference between them was increased when shivering occurred.
8. In comparison with the adrenal arterial blood, the reflux venous blood showed higher temperature, and T. T. G. increased this temperature difference in the earlier stage of the fever reaction.
In these experimental results, the author indicated several valuable utilization of this new instrument. From results described above, the author concluded the existence of the several time series which was closely correlated with the temperature regulation of the body. It is suggested that the nature of this wave may be some circulatory changes correlated with arteriovenous anastomoses and concerning regulation of them, symathetic adrenal control must be postulated.

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