岡山大学温泉研究所 Acta Medica Okayama 0369-7142 24 1959 三朝温泉に於ける湯治概況調査 80 86 EN Tohaku Wakutani Kinshi Matsumoto Yasuhisa Yamamoto Misasa Hot Spring is one of the most famous radioactiye hot springs in Japan. A general survey of the spa treatment at Misasa Spa was carried out in Feburary, 1957. The informations we have gathered may be summarized as follows: 1). The number of the spa visitors seeking for curative treatment was almost equally divided between men and women and the majority of the spa visitors was over 50 years old. 2). 65% of the spa visitors came to this hot spring with the specific purpose of balneotherapy. 19.3% came for rest, 13.3% for the purpose of after-care. 3). Those who visited Misasa Spa for the first time were 44.7%, the rest being those who visited this spa over 2 times. 18.3% of them had consultation with or were under the direction of a physician. 4). The length of time they stay at this spa for curative treatment: 41.6% of the spa visitors stay for 8〜14 days, 17.9% of them 15〜20 days and 31% of them over three weeks. 5). About 74% of the spa visitors bathe 3 to 5 times a day for curative treatment, and 82% of them drink hot spring water. 6). Symptoms of bathing reaction such as generalised fatigue, constipation, loss of appetite, joint pain, abdominal pain and so on were observed in 50% of the spa visitors. No potential conflict of interest relevant to this article was reported.

岡山大学温泉研究所 Acta Medica Okayama 0369-7142 25 1959 関節リウマチの貧血に関する臨牀的研究 53 69 EN Yasuhisa Yamamoto Anemia of moderate severity is commonly present in patients suffering from rheumatoid arthritis, but one to which little attention has been paid and despite its frequency the exact mechanism of its production is uncertain. Anemia in rheumatoid arthritis is refractory to anti-anemic therapy. The presence of anemia may hinder adequate physical or orthopedic treatment and may produce a degree of lassitude that considerably aggravates the joint disability. This anemia, therefore, seemed worthy of study and investigations of three aspects are reported here: 1. Changes in peripheral blood, bone marrow, liver function and gastric acidity. 2. Alternations in iron metabolism. 3. Balneotherapy and anemia in rheumatoid arthritis. I. Peripheral Blood Picture, Liver Function, Serum Protein Fraction and Gastric Acidity. 1. The peripheral blood and bone marrow. The number of erythrocytes is 558〜216×10(4)/c. mm. (average:402×10(4)/c. mm.), hemoglobin-content:110〜40% (average: 78.6%), and the color index is about 1.0. The anemia of rheumatoid arthritis treated is mostly normochromic. The white blood cell count is between 11200 and 3720/c. mm. (average: 7504/c. mm.), and the number of leucocytes in 80% of the cases ranges within the normal limits. Eosinophilia is observed 27% of the cases. Films of the sternal marrow showed no major abnormality in the eight cases examined. Several minor points, however, deserve mention. The nucleated cell count was diminished in seven cases examined, and the decrease of normoblasts in bone marrow would explain the reduced red cell count in peripheral blood. The myeloid series showed a relative increase. 2. Liver function tests and gastric acidity. To illustrate the possible appearance of liver function disturbances in connection with rheumatoid arthritis, the author has made different liver function tests on patients suffering from this disease. From the results it appears that in protein metabolism tests more than 83% of the cases gave abnormal albumin/globulin ratios and Takata's and erthrocyte sedimentation reactions. The detoxication capacity determined by hippuric acid synthesis tests had decreased in 25% of the cases examined. The dye excreting capacity, determined by the bromsulfalein tolerance test, was found to be reduced in 64% of the cases examined. The urin-urobilinogen test showed positive in 28% of the cases. In all cases the insulin sensitivity test gave pathological readings. Of 40 cases examined, anacidity of gastric juice was observed in 17 cases, subacidity in other 10 cases and normacidity, hyperacidity in remammg 13 cases. Thus, a decrease in the gastric acidity was found to occur in 67.5% of the cases. 3. Serum protein fraction. The total serum protein of 31 cases with rheumatoid arthritis appeared to be on the same level as in normal material. Serum protein fraction was determined in 19 cases by paperelectrophoresis. In rheumatoid patients, albumin fraction of serum protein decreased and γ-globulin fraction increased in all cases examined, compared with the data of normal subject as a control. Alubumin/globulin ratio of rheumatoid arthritis was below the 5% rejection limit of normal value. No potential conflict of interest relevant to this article was reported.

岡山大学温泉研究所 Acta Medica Okayama 0369-7142 26 1959 関節リウマチの貧血に関する臨牀的研究 第3報： 関節リウマチ貧血に及ぼす温泉治療，各種貧血治療剤の影響 50 63 EN Yasuhisa Yamamoto III. The Effects of Balneotherapy and Antianemics on Anemia in Rheumatoid Arthritis 1. Balneotherapy: The author investigated the changes of the peripheral blood picture, erythrocyte sedimentation rate, numbers of finger-ring (Wheatsheaf's ring-test) and grasping power (by means of hand-dynamometer or sphygmometer) before and after baneotherapy. The regimen of spa treatment in our hospital includes bathing in radioactive hot spring (42-3°C. in temperature)two or three times a day, local mud bath or mud pack (once or twice a day, massage and drinking of spring water. These measures performed for one or two months. When the spa treatment has finished the erythrocyte count and Hb-content of rheumatoid patients increased in 61% of 33 cases examined comparing with before treatment, leucocyte count tended to shift to normal and E.S.R. decreased in 58% of the cases. The swelling of the finger joints diminished. 2. Oral iron therapy: In previous report, the author verified that there exist simple iron deficiency anemia in some cases of rheumatoid arthritis. Oral iron therapy responded well in such cases, but the majority of cases were resistant to oral iron. 3. Transfusion of blood in rheumatoid anemia: The author transfused 100 ml. of blood once a day for 5-10 days in 11 rheumatoid anemic patients. By the treatment of transfusion, the findings in peripheral blood improved and E.S.R. decreased. No potential conflict of interest relevant to this article was reported.

岡山大学温泉研究所 Acta Medica Okayama 0369-7142 26 1959 関節リウマチの貧血に関する臨牀的研究 第2報： 関節リウマチ患者の血清鉄量の消長について. 付血清銅量 31 49 EN Yasuhisa Yamamoto II. Iron Metabolism 1. The serum iron: The serum iron was estimated by the method of Umemoto and Yamamoto (by means of o-nitroso resorcinmonomethylether) The average serum iron level of 33 cases with rheumatoid arthritis was 47γ/100 ml., and in 27 of 33 cases (82%) the serum iron levels were shown to be below　the lower limit of the normal range (5% rejection limit: 54-141γ/100 ml. ), but the concentrations of serum iron of neuralgias (degenerative Spondylosis, sciatica and painful shoulder) were mostly within the normal range. 2. Iron absorption: To investigate the possible role of poor absorption in preventing a response to oral iron therapy, the changes in serum iron were followed after a test of iron by mouth in 16 caseS with rheumatoid arthritis. The test dose was 1 gm. of reduced iron given with 30 mI. of lemonade-pepsin solution to preserve the iron in the ferrous state and obviate the effects of possible achlorhydria in rheumatoid patients. The results may be grouped under three headings: a) Large rise in serum iron: good adsorption. Three caseS (19%) showed a very large rise in serum iron after the test dose, which is similar to simple iron-deficiency anemia. b) Slight rise in serum iron: presumed poor absorption. Six cases (38%) showed a very small or negligible rise after the test dose, so that at its peak the serum iron was below the normal range. c) In the remaining 7 cases, a maximal rise in serum iron after the test dose was within the normal range. 3. The iron-binding capacity of the serum: The iron-binding capacity of the serum was estimated by means of intravenous injection of Gluferricon (Fe content: 10 mg.). The mean total iron-binding capacity of the serum in the present 13 cases with rheumatoid arthritis was 273γ/100ml., virtually the same as the normal figure (287γ /100 ml.). The degree of saturation of the iron-binding protein with iron was found to lie between 18 and 45% (average: 34%) in control sUbjects and between 7 and 24% (average: 16%) in rheumatoid patients. 4. The serum copper: The serum copper was estimated by means of diethyldithiocarbamate in rheumatoid arthritis with the following results. Healthy subjects: men (15 cases): mean 89.9±14.8γ /l00 ml., women (15 cases): mean 99.9± 12.6γ/100 ml. There is no significant difference between the two. In 10 of 17 cases (57%) with rheumatoid arthritis, the serum copper levels were shown to be above the upper limit of the normal range (57-138γ/100 ml. ・・・5% rejection limit), neuralgias were mostly (92%) within the normal range. The results of investigations upon alternations in iron metabolism of rheumatoid anemia are reported. 1. The serum iron concentration was usually reduced. 2. The intestinal absorption of iron after a single dose of 1 gm. of reduced iron was variable. Strong presumptive evidence of impaired absorption waS recognised in many cases, but some cases gave the excellent absorption. From these results, it seems that simple iron deficiency exist in some anemic caseS of rheumatoid arthritis. 3. The total iron-binding capacity of the serum was slightly reduced. 4. The degree of Saturation of iron-binding protein with iron was below nornal. 5. The serum copper concentration waS usually elevated. No potential conflict of interest relevant to this article was reported.

岡山大学温泉研究所 Acta Medica Okayama 0369-7142 39 1970 温泉入浴の血清鉄値に及ぼす影響について 61 75 EN Yasuhisa Yamamoto The author investigated the effect of radioactive hot spring bathing on serum iron values. The serum iron values were measured by Umemoto-Yamamoto's method using o-nitrosoresorcin monomethylether, as a colour-developing reagent. The chemical compositions of the spring water used is as following: pH : 7.04, Rn : 38-151x10(-10)curies/l, K(+) : 14.0, Na(+) : 540.2, Ca(++) : 61. 2, Mg(++) : 6.6, Fe(++) : 89.0, AI(+++) : 0.1, Cl(-) : 709.5, S0(4)(--) : 179.5, HCO(3)(-) : 226.7, H(2)SiO(3) : 89.0, HBO(2) : +, CO(2) : 29.5, totaling 1,827mg/kg. 1) Single bathing: The iron values in the serum were measured before and after 0, 1/2, 1 and 2 hours after the radioactive thermal bathing for 10 minutes in water of 41 ±2℃ in temperature. Single thermal bathing showed no significant effect on the serum iron values in healthy hnman subjects, but the serum iron concent:'ations in healthy white rabbits tended to decrease following single thermal bathing and to remain at a decreased level for 1/2 to 1 hour, and returned to normally within 2 hours from the time of the bathing (Table 1, 2 and Fig. 1, 2). 2) A series of baths: The author examined the serum iron values of patients with rheumatic disorders before and 3rd, 7th, 14th, 21st and 28th days after in the course of "a series of baths" in radioactive hot spring. Patients bathed in water of 41 ± 2℃ in　temperature, for 5-10 minutes, 2 or 3 times daily. A　fall in the serum iron values was seen on the 3rd to 7th days. At that time the pattern of iron absorption from intestine showed a iron dificiency anemia type. The rate of absorption of iron was rapid. At about the 14th day, the serum iron values of patients tended to increase but unbound iron-binding capacity of the serum decreased. Subsequently, the serum iron values returned to the initial levels between the 21st and 28th day (Table 3, 4, 5, and Fig. 3, 4, 5), 3) It is said that the reticulo-endothelial system plays an inportant part in iron metabolism. The author injected 5 ml of Indian ink into the aural vein of rabbits for the purpose of blocking the reticulo-endothelial system. These procedures were carried out once a day for 7 successive days. The rabbits with "a blockade of R. E. S." had no significant change in the serum iron values during a series of baths. From what has been stated in the above, it may be said that bathing in radioactive hot springs regubtes the iron metabolism of patients with anemia and brings about the acceleration of the medullary function. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 1 1959 脳のglucose代謝におよぼすamino酸の影響に関する研究 第2編 癲癇患者大脳皮質のglucose代謝およびそれにおよぼす種々のamino酸の影響について 313 318 EN Yasuhisa Yamamoto The influences of the free amino-acids upon the glucose metabolism were investigated in the cerebral cortex removed from the epileptogenics and non-epileptogenics. Glucose metabolism decreased in the epileptogenic cerebral cortex, compared with the nonepileptogenic one. In the non-epileptogenic cerebral cortex, these free aminoacids accelerate the utilization of glucose, in the following order of γ-aminobutyric acid, aspartic acid, asparagine, glutamine, glutamic acid from the most to the least, while in the epileptogenic one in the order of aspartic acid, glutamic acid, asparagine, γ-aminobutyric acid and glutamine. These amino-acids have more pronounced function to accelerate the glucose metabolism in the epileptogenic brain than the nonepileptogenic. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 1 1959 脳のglucose代謝におよぼすamino酸の影響に関する研究 第1編 潜在性脳局所anaphylaxis家兎大脳皮質のglucose代謝およびそれにおよぼす種々のamino酸の影響について 305 311 EN Yasuhisa Yamamoto There are many kinds of free amino-acids in the brain, most of which are glutamic acid, glutamine, asparatic acid. asparagine, γ-aminobutyric acid etc. The author has investigated the influences of these amino-acids upon the glucose metabolism in the brain of the normal and the cerebral local anaphylactic (C. L. A.) rabbits. Glutamic acid, glutamine and γ-aminobutyric acid accelerate the utilization of glucose in the brain of the normal as well as the C. L. A. rabbits, aspartic acid and asparagine accelerate that of glucose in the C. L. A. rabbits, while they have no influence on that in the normal. It is clarified that all of these amino-acids have the function to restore the decreased utilization of glucose in the C. L. A. rabbits to more than the normal level. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 72 4 1960 脳のglucose代謝におよぼすamino酸の影響に関する研究 第3編 痙攣家兎大脳皮質のglucose代謝およびそれにおよぼすamino酸連続投与の影響について 1255 1260 EN Yasuhisa Yamamoto Convulsions were repeatedly caused by electrical stimulation in rabbits. Total free amino acids contents in these rabbits showed no fluctation, while glucose metabolism decreased like as in those with latent cerebral local anaphylaxis and human epileptics. The glucose utilization was cured to normal level by continuing injection of Glutamic acid, GABA, and Asparagine, but total amino-N changed scarecely. It is an important fact, that free amino-N content increased by GABA injection in rabbits with convulsion. No potential conflict of interest relevant to this article was reported.