A report has been made previously by Abe, a member on the staff of our laboratory, that the stimulation of the reticulo-endothelial system by successive spa bathing is the result of a nonspecific stimulating action produced by spa bathing.
The author attempted the present experiment with a view to obtain some information on the mechanism of the effect of spa bathing on vital resistance.
In Section I are described the following experiments: A given quantity of coli bacilli was injected into the auricle vein of a rabbit.
The effect of spa bathing immediately after injection on the function of the liver to seize bacilli and that on its function to counteract bacilli were observed by counting the number of bacillus colonies in the liver 10 minutes, 2 hours and a half, and 4 hours after injection respectively.
In Section II, the effect of spa bathing on the functions of the liver was studied indirectly by counting the number of bacillus colonies in the blood 4 times, namely, 10, 20, 30 and 40 minutes after injection of coli bacilli.
In Section III, the effect of spa bathing on the antiseptic function of the blood was observed in the rabbit by the Jinnai's method.
In the experiments described in Sections I and II, it was found that the single bathing and 7-day successive bathing in “Genzo-yu” (acid vitriol spring) were most effective in producing the stimulation of the function of the liver to seize bacilli and that to counteract bacilli, followed by “Unagi-yu” (alcaline muriated sulphur spring) and the spring in our laboratory (muriated saline spring).
The stimulation of the function of the liver to counteract bacilli was pronouncely observed in the bathing in “Unagi-yu”.
In the experiments described in Section III, it was found that 15-day successive bathing in “Genzo-yu” greatly stimulated the anti-septic function of the circulating blood, while that in “Unagi-yu” slowly and slightly stimulated it.
It has been made clear from the above observations that the spa bathing plays an important role of intensifying the protective action of the living body against infection, by stimulating the protective action against infection of the liver to seize or to counteract bacilli and by intensifying the antiseptic function of the circulating blood.
Such action usually runs parallel with the nonspecific stimulating action of the spring, which is most intensive in “Genzo-yu”, followed by “Unagi-yu”.
These actions and stimulations observed are suggestive of the fact that in the case of healthy person, spa bathing is not only of use in strengthening his resistance against infection from outside, but also effective in therapy of infection; they endorse the therapeutic utility of spa.

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By using healthy persons and rabbits, a study was made of the effect of spa bathing on the pituitary adrenocortical function with the excreted urinary 17-ketosteroid hormone (17-KS) as index, and the following conclusion was reached:
1) The excreted urinary 17KS was, on an average, 0.58mg/day in male adult rabbits, 10.08mg/day in healthy men and 8.40mg/day in healthy women.
2) Compared with fresh water bathing, the effect of the bathing in muriated saline bitter spring at our laboratory on the rabbits was observed 7 to 10 days after initiation in the form of an increase in the excreted urinary 17KS, it tended to decrease on the 14th day, but considerable effect continued to be seen even 7 days after discontinuance of bathing. In most cases, a trifle transitory decrease in the excreted uninary 17KS may be observable in the early stage of balneological cure, but it should be interpreted as being a functional alteration in the adrenocortical function rather than as an obstruction in it. Compared with 5-minute bathing, 15-minute bathing sometimes produces a sudden loss of body-weight as well as an abrupt decrease in the excreted urinary 17KS, resulting in death in some cases. Consequently. 15-minute bathing seems to be too excessive for rabbits as stress.
3) Successive bathing produces in healthy persons a transitory decrease in the excreted urinary 17KS in its early stage.
It begins to increase then, reaching the maximum quantity 7 to 10 days after initiation. On the 14th day, it tends to decrease again in most cases. No remarkable difference is observable in the average value between spings of different chemical constituents, but it is observable between different bodies.
4) Such effects of spa bathing as those mentioned above are less apparent in the old-age group than in adult group.
It is probably because there had been prostration in the pituitary adrenocortical function that the old-age group could not show sufficient reaction to the stimulation of spa bathing.
5) It may be said from the above observations that spa bathing, by acting on the living body as a kind of stress, vitalizes the adrenal cortex to expedite the excretion of corticoid hormone, which results in therapeutic effect.
6) This also accounts partially for the effect of spa bathing on rheumatic diseases, and we can understand from this why spa bathing is made use of in combination with steroid hormone which has been in wide use recently, in order to regulate the period in which the drug is to be used, to intensify its effectiveness and to prevent the reactivation of the disease after the discontinuance of the administration of the drug.

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A general survey and the results of some medical investigations of the spa treatment at Ginzan Spa may be summarized as follows:
1) Of 115 persons with whom we consulted, women were larger in number, the majority of them being from 20 to 40 years old and suffering from digestive diseases.
2) The spa visitors are mostly inhabitants of Yamagata Prefecture (especially of Yamagata City), the majority being farmers.
3) 25.7% of the spa visitors come to this hot spring with a specific purpose of balneological therapy, 35.8% come for rest, 31.2% for recreation and 5.7% for the purpose of after-care.
4) Those who visit Ginzan Spa for the first time were 52.4%, the rest being those who visited this spa over two times.
Only 4.8% of them had consultation with or were under the direction of physician.
5) The length of time they stay at this spa for curative treatment is comparatively short. 56.5% of them stay for less than 5 days and 26.4% from 6 to 8 days.
6) About 69% of the spa visitors bathe 4 to 6 times a day for curative treatment, 20.4% less them 3 times and 10.6% more than 7 times a day.
7) Only 17.1% of the spa visitors drink hot spring water for curative treatment.
8) Symptoms of bathing reaction were observable in 30% of the spa visitors, though small in number and slight in degree.
9) Hot spring bathing in this spa (at 42°C for 5 minutes) is effective in lowering both the maximal and minimal blood pressure; the higher the blood pressure is, the greater the degree of lowering.

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Soaking one hand into a water bath at 6° or 42°C, reflective vasoconstriction occurred on the finger-tip on the other side was investigated with digital photoelectric plethysmography in 45 cases of healthy control, 10 cases of Buerger's disease, 6 cases of Raynaud's disease, and 58 cases of hypertension. And the influence of thermal baths on vascular reaction in hypertension was examined.
Results obtained were as follows:
1) An initial vasoconstriction was recognized both on 6°C and 42°C stimulation.
2) The time from the moment of the thermal stimulation till the minimum pulse amplitude in the initial constriction was described as ΔT. And ΔA was calculated by following formula:
ΔA=(Amplitude before stimulation-Minim. amplitude/Amplitude before stimulation)×100%
i) No correlation was observed between ΔA and ΔT in both warm or cold stimulation.
ii) No significant correlation was established between 6°C ΔA and 42°C ΔT.
iii) A significant correlation was proved between 6°C ΔA and 42°C ΔA.
3) In Buerger's disease a prolongation of 6°C ΔT was observed compared with that in healthy controls.
In Raynaud's disease prolongation of 6°C ΔT and reduction of 6°C ΔA were proved in comparison with the data in the healthy adults.
4) In hypertensive patients 6°C ΔA was proved smaller than that of the control and a significant correlation was shown between 6°C ΔA and fall of skin temperature on the finger tip of one side by soaking the other hand into 6°C water. Hardly recognized was a correlation between 6°C ΔA and results of cold presser test.
5) 6°C ΔA increased after warm bath. And by a series of daily thermal baths at the Kageyu Spa (simple thermal springs) hypertensive patients showed the most sensitive reaction concerning 6°C ΔA and 6°C ΔT about the end of the first week.
6) In hemiplegie patients, 6°C ΔA on the affected side was proved to be smaller than that on the healthy side, and after a thermal bath at the Kageyu Spa 6°C ΔA of the affected side increased more than that of the healthy side.
7) In hypertension, patients with larger ΔA showed more marked fall in blood pressure after a series of thermal baths than patients with smaller ΔA.

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To check the changes in the appearance of the loops of the small intestine, serial indirect (6×6cm size) and direct photographies were used.
After ingestion of barium test meal, exposures were made every 15 minutes for a period of 1 hour, and then every 30 minutes for 3.5 hours; (that is to say, 4.5 hours after initial ingestion of barium). Fluoroscopic examination was an essential part of the procedure.
The results were summarized as follows
(A) In 136 cases of chronic diarrhea, which had no abnormal changes in the colon, 39 cases (28.7%) showed normal appearance of the samll intestine. However, in 92 cases (67.6%), roentgen examination revealed abnormalities in the mucosal pattern, the tonicity and the motility of the loops in various degrees.
1) In conformity with these abnormal appearance roentgen features were classified into following 6 types: Type I: coarsening of the mucosal folds (7 cases-5.1%), Type II: hypersecretion (16 cases-11.8%), Type III: mixed type—coarsening of the mucosal folds and hypersecretion (85 cases-62.5%), Type IV: hyperkinesis (7 cases-5.1%), Type VI: non pathologics (10 cases-7.4%).
Type I, II, and III, (79% in total) were considered as inflammatory changes, and type III, as the most common feature of the enteritis.
2) In general, the transit time of the small intestine had a tendency to be accelerated in cases with chronic diarrhea, although it was relatively delayed in a few cases. Transit time comparatively shortened in type III, but prolonged in type IV.
3) Emaciation and abdominal pain was mainly associated with the changes of type II and III, while the latter symptom was most frequently encountered in cases with accelerated transit time.
(B) In chronic obstipation 44% of 50 cases showed roentgenologically normal appearance of the loops of the small intestine, but cases with I (2 cases-4%), type II (5 cases-10%) and type III (10 cases-20%) were also found, including a few habitual laxative employers.
The transit time was normal or slightly delayed in the cases with chronic constipation.
(C) A mixture of 150cc of liquid paraffin and 150gms of barium sulphate powder was given to 5 healthy subjects. All of them showed abnormal feature analogous to type II.

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Response of the colon to low frequency currents was studied roentgenologically.
(A) Modified rectangular currents (10-1000 cycles per second).
A moist pad electrode, 5cm wide and 10cm long, was placed on the abdomen and another one of equal size directly opposite on the back of the patient.
Either currents of 10 or 1000 cycles/sec were applied for 11 minutes. The current strength was 3mA.
The results were summarized as follows:
1) Roentgenologically acceleration of motility of the colon was recognized in almost all of the cases, without regard to various conditions of the colon before the treatment.
2) The currents of 10 cycles/sec showed more favorable results than these of 1000 cycles/sec.
3) Particularly, when the former was applied on the lower abdomen (positive electrode on the back of the patient), change of the roentgen figure of the colon was most obvious.
4) After the start of the electrification the acceleration of the motility of the colon appeared 5 minutes later and gradually increased for 10 minutes. When the current was stopped, the accelerated motility diminished gradually to the previous state of the colon in 20 minutes.
(B) Slow sinusoidal current (20 cycles per minute).
Two pad electrodes, 10cm wide and 15cm long, were used, similarly to (A).
This current has a wave form with ascending time of 1000ms, current strergth of 25mA, and the treatment was given for 16 minutes.
The results were as follows:
1) Acceleration of the colon was recognized, regardless of the condition of the colon before the treatment.
2) A current increasing gradually in strength resulted usually in a success to enhance the motility of the colon.
3) After the start of the treatment colon movement was promoted 10 minutes later, and gradually increased for 15 minutes.
When the current application was ceased, the accelerated motility diminished gradually. but even 20 minutes later a tendency of acceleration was recognized in roentgen picture.

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A significant enlargement of the thyroid was proved in the schoolchildren of the radioactive spring area, such as Spa Misasa, Spa Masutomi, Kawauemura near Spa Ena, and Okuwamura near Spa Shikanoyu, as compared with the results in the non-radioactive control area, such as Tokyo City, Tadaomura, Funabashi, Matsumoto City, and Saku district.
Both in these radioactive spa area and in the control districts, pH, radon, iodine, calcium, and chloride contents of the ground waters were determined and I/Cl ratio was calculated. But neither iodine deficiency nor calcium excess were found in the ground waters of these endemic thyroid swelling area.
The thyroids of male rabbits fed with a strongly radioactive spring water of Masutomi (Rn content about 11.000×10^-10curies/1) for 150 days showed histologically hyperplasia, however no apparent increase of radioactivity was proved in these thyroids by G. M. counter.
The oxygen uptake of the tissue, chiefly of the sliced thyroid tissue, was measured by means of Warburg's apparatus under various experimental conditions.
Insertion of Thoron source (Monazite) in the side-chamber suppressed the oxygen consumption of the tissue and its removal showed a kind of rebound phenomenon, namely a slight accelerated respiration.
X ray irradiation (100-200r) from outside the main-chamber showed a similar result after cessation of X irradiation.
L-Thyroxine increased the tissue respiration and its optimum concentration was observed at 3.0γ/cc.
The sliced horse thyroid incubated in TSH solution showed increased respiration without lag time.
By simultaneous application of Thoron with l-Thyroxine or Thoron with TSH, suppressing of respiration by Thoron covered the respiration accelerating action of l-Thyroxine and TSH.
The sensitivity of the thyroid to the respiration accelerating action of l-Thyroxine was elevated after removal of preliminary applied Thoron source.
The glucose and inorganic phosphorus consumption and lactate formation were measured using aliquots of media in Warburg's cells.
The respiratory quotient of the sliced horse thyroids was also determined by means of Terui's apparatus. Ringer's solution was used as suspending medium. Values obtained were 1.08, 1.15, 0.97 and 1.07 on an average.
The wet weight/dry weight ratio of the sliced horse thyroid tissue was determined, average 1/3.2.
By the above mentioned results, it was concluded that thyroid enlargement of the schoolchildren in the radioactive spa area could not be explained as a result of iodine deficiency or calcium excess in the ground water.
But prolonged action of the small amounts of radioactive elements in the ground waters probably decreased tissue oxygen uptake and the diminished tissue respiration might result in the hypertrophy of the thyroid.

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Influence of various kinds of baths upon the electrocardiogram of hypertensive patients (51 cases) and convalescent inpatients (64 cases) who had been inhibited from bathing at least for one month to 16 months was studied and the results obtained were as follows.
(1) By taking a full immersion bath in usual water or in thermal water of Kageyu for twenty minutes at 39°C, a few of the hypertensive patients showed a transient, slight electrocardiographic changes.
Namely slight lowering of ST-T was seen in 7 of the 25 cases by the former bath, and 1 of 26 cases by the latter.
(2) By taking a bath at 42°C for fifteen minutes reconvalescents showed no notable change but by 45°C bath for five minutes only one among twenty-one subjects showed a transient undesirable change electrocarbiographically.
(3) By takjng a cabinet vapor bath at 45°C for fifteen minutes only two among twenty-one subjects showed a transient right bundle branch block but no ST-T change was found at all.
(4) By taking electrical four cell bath using galvanic current of about 6-8 milliamperes at 45v. no e. c. g. -change was proved.
(5) The effect of exercise on 7 patients with myocardial disturbances, was compared with the effect of a hot bath at 42°C for fifteen minutes and no significant difference was found between these two procedures.
(6) Serum sodium and potassium were measured in 53 cases of the above-mentioned subjects before and after bathing. Serum electrolytes showed changes and no constant relation with the e. c. g. -changes was proved.

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The author made a research on the biochemical, histological and serological effects of the acid hot spring bathing at Tamagawa Spa (a acid vitriol sulphur spring) on the liver of rabbits. The condition of the bathing was to shave the back of rabbits and to give them a serial bathing for 10 days (10 minutes once a day at 42-43°C), and as control to give other rabbits a fresh water bathing under the same condition as mentioned above.
1. Functional changes of the liver.
1) Blocd sugar: The group of the hot spring bathing showed same wavy changes of blood sugar values as the group of the fresh water bathing, while there was a difference in the phase of the change between the two groups.
2) Blood plasma protein fractions: Following changes were observed-decrease of T. P. in the early stadium and its later increase, increase of Globulin, decrease of Albumin with its lowest value in the middle stadium and its gradual recovery in the later stadium, increase of α-Gl, β-Gl and φ with their peaks in the middle stadium, and decrease of γ-Gl in the early stadium and its later gradual increase.
3) Iodate reducing power of the blood: It showed no definite change in the early stadium of bathing, and then it took a tendency of increase as days of the bathing went on, but it restored to its normal state soon or later after the 10 days' serial bathing was over.
4) Serum Co-reaction: Serum cobalt changed positive to the leftside in both groups, but in the group of hot spring bathing it was stronger than in the group of the fresh water bathing.
5) Blood cholesterol: Total-cholesterol-and free-cholesterol-values decreased during the whole course of the serial bathing, while ester-cholesterol-values showed a gradual increase taking a wavy change. E. Q. (%) increased, therefore, during the whole course of the serial bathing.
6) Liver V. B₂: In the early stadium decrease of total-V. B₂ and FAD, and increase of FMN and FR were observed, but in the middle and the later stadium increase of total-V. B₂ and FAD, and decrease of FMN and FR were observed. These later changes were still more remarkable after the 10 days' serial bathing was over.
7) BSP-test: BSP-test showed negative reaction in both groups.
8) The phagocytosis of trypan-blue by Kupffer's stellate cells: At the early stadium of bathing it decreased for a while, and then gradually increased and remarkably increased at the beginning of the later stadium.
2. Histological changes.
a) In the liver it was proved that the swelling and increase of Kupffer's stellate cells and the infiltration of the mononuclear cells in Glisson's sheaths were more remarkable in the group of the hot spring bathing than in the control group.
The increase of Kupffer's stellate cells was almost parallel with that of phyagocytosis of the trypan-blue. The swelling and cloudiness of the liver cells and the hyperemia of the liver were a little stronger in the group of the hot spring bathing than in the control group.
b) In the kidney, the hyperemia of the kidney and the swelling, cloudiness of the epithelium of uriniferous tubules and its desquamation in the group of tho hot spring bathing were stronger than those in the control group.
c) In the spleen and lymph nodes, the reticulo-endothelial cells increased, but it was difficult to observe the differences of degree between the two groups.
d) In the bone-marrow, the hematopoesis was a little stronger in the group of the hot spring bathing than that in the group of the fresh water bathing.
The histological changes of these organs gave almost common histological findings in both groups except their quantitative differences, and they were observed to be momentary and reversible.
3. Patho-anatomical findings in the parts affected by the dermatitis at Tamagawa Spa, and serological and biochemieal studies on the production of the auto-antiobody.
1) The occurrence of the

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In the previous reports, using Warburg's apparatus, the author proved that Thoron inhibits oxygen consumption of erythrocytes, of the liver, kidney, and brain homogenates of grown-up rabbits and that this inhibition is reversible. After hemolysis of erythrocytes by adding distilled water or after centrifuging the homogenates of the liver, kidney, and brain, their oxygen consumption decreased outstandingly and then inhibition by Thoron became hardly proved.
Then using a mineral water of the “Spring Dairokuten” of Masutomi (Rn: 837×10^-9-739×10^-9 curies/1), effect of the natural radioactive water on tissue oxygen consumption was investigated when the mineral water was mixed with the suspension in Ringer's solution of the human erythrocytes or homogenates of the liver, kidney, and brain of rabbits.
The fresh mineral water of Masutomi depressed oxygen consumption of human erythrocytes and the brain homogenate of rabbits, but it accelerated oxygen consumption of the liver and kidney of rabbits.
The aged mineral water of Masutomi, which lost its radioactivity by storing over a month, promoted the oxygen consumption of the human erythrocytes and of the liver and kidney of rabbits, but it decreased the oxygen consumption of the brain.
Then an artificial mineral water was made up after the analytical table of Masutomi mineral water. And effect of the artificial mineral water on the oxygen consumption of the liver, kidney, and brain homogenates of rabbits were studies with the same method as above.
The artificial mineral water without iron and radon showed a decrease of oxygen consumption of the liver, kidney, and brain homogenates. However, the artificial mineral water, of which only radioactive components are excluded, accelerated oxygen consumption of the liver and kidney homogenates of rabbits, but it decreased the oxygen consumption of brain.
In the present study, effect of the internal use of a natural radioactive water on tissue oxygen consumption was studied. Grown-up rabbits were given daily 10ml per kg body weight of Masutomi mineral water for five months.
The administration of the radioactive mineral water produced a decrease of -42.6%, -19.6%, -5.1%, and -49.7% respectively in the oxygen consumption of the liver, kidney, brain, and bone marrow of rabbits at the end of 5 months.
The oxygen consumption of the bone marrow of rabbits, to which Hontanikawa river water was given with same method as above, was also reduced to -27.1% of the control without drinking.
As river water of Hontani contains only minor amount of radioactive element (Rn: 1.27×10^-10 curies/1), the above-mentioned decrease in the oxygen consumption of the bone marrow, kidney, and liver can not be attributed to the effect of radioactive agents in the mineral water alone.
Prolonged administration of stored mineral water of Masutomi (10ml to rabbits daily) produced no apparent inhibition of tissue oxygen consumption.

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