Prevalence of tuberculosis in the inhabitants of Tokunoshima-Town was precisely investigated by the analysis of tuberculosis cases in the household-members. Results obtained are as follows;
1) Number of households, in which all family members were examined, was 4, 584, and the rate of the households having tuberculosis cases requiring medical treatment to the total was 7.1 % and was lower than the average of Japan.
2) Accumulation rate of the household having tuberculosis cases requiring medical treatment was as same as the average of Japan, showing the figure of 1.09.
3) To the total 275 households having tuber culosis cases requiring medical treatment, the rate of those having 3 family members to be treated in the same household was 0.7%, and that of 2 was 8.0%, respectively. In the remaining 251 households (91.3%) was found only one tuberculosis case requiring medical treat ment. These rates were as similar as the average of Japan.
4) Positive rate and the rate of palpable induration of tuberculin reaction in children living in contact with tuberculosis family members to be treated were higher than those without tuberculosis case.
5) Among the households with tuberculosis children requiring medical treatment, 15.5% were those in which the other family members were found to be tuberculosis cases requiring medical treatment. This rate was, of course, higher than that of the household without any children requiring medical treatment. Most of the tuberculosis cases requiring medical treatment in the household were either father or mother. Medical control of the members in the household with tuberculosis cases requiring medical treatment is highly important in preventing children from the infection of tuberculosis.

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A strain of acid-fast bacilli was isolated from a patient with “BCG-lupus”. No identification of this strain could be made by morphological studies of bacilli or colonies nor by various other cultural investigations.
Neither 1.0 mg of the strain nor BCG inoculated subcutaneously or intracutaneously in rabbits, guinea pigs, mice and chicken showed any affection, while the same treatment with H37Rv brought changes in the organs of all these animals except the chicken.
The results of the niacin and nicotinamidase tests of this strain were similar to those of BCG, but different from those of H₃₇Ra. The cord-formation of the strain was almost equal to that of BCG and Aoyama B. (A low virulent human strain used for old tuberculin in this country). Kf value of this strain was similar to that of BCG and H₃₇Ra, but was lower than that of H37Rv. The strain was stained with neutral red as faintly as BCG and Aoyama B, but more feebly than H₃₇Rv and H₃₇Ra. The catalase activity was as strongly positive as BCG, but weaker than that of H₃₇Rv and Aoyama B. The type specificity of the strain was not clearly demonstrated with the purified tuberculin as compared with that of BCG, Aoyama B or H₃₇Rv.
The strain was susceptible to streptomycin, paraaminosalicylic acid, isoniazid, and sulfisoxazole. In Dubos' media and Besredka's media, growth appeared with an inoculum of 10^-6 mg or more of the strain and with the same quantity of BCG, while growth of H₃₇Rv and Myc. smegmatis appeared with an inoculum of 10^-8 mg. On 1%, Ogawa's egg media the growth of the strain was not distinguishable from that of H₃₇Rv, Aoyama B, BCG, and Myc, smegmatis.
These clinical, bacteriological, and biochemical findings led us to the assumption that the strain obtained from the lesion of the patient is BCG.

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It is very important to know the best combination of chemotherapeutic agents to chronic resistant far advanced pulmonary tuberculosis. We compared the results of the following 7 types of chemotherapy in the treatment of 74 patients of far advanced pulmonary tuberculosis with resistant tubercle bacilli.
i) INH single therapy…6 cases
ii) INH-PAS therapy…7 cases
iii) INH-PZA therapy…9 cases
iv) SM-PAS-INH therapy…18 cases
v) SM-PAS-INH-Sulfadrug therapy
…14 cases
vi) SM-PAS-INH-PZA therapy…9 cases
vii) INH-PZA-Sulfadrug therapy…11 cases
The results were observed for 3 to 6 months.
Generally speaking, two drug combination therapy is better than one drug single therapy, three drug combination therapy is better than two drug combination therapy, and four drug combination therapy is better than three drug combination therapy. Since most of the patients had SM-, PAS-, or INH-resistant tubercle bacilli, four drug combination therapy is not so effective as expected. Sulfadrug, PZA…to which the tubercle bacilli of the patients were not resistant…and INH combination therapy is the most effective among these 7 types of therapy, but the complications were most frequently observed in this type.
Consequently, we considered that new types of combination of newer antituberculous drugs (KM, CS, 1314TH etc.) should be surveyed.

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Avian mycobactria (Strain AVT) was made resistant to isoniazid by successive transfers on Sauton synthetic media containing 100 micrograms of this drug per ml. Resistant cells thus obtained were cultured on metal-enriched Sauton media with or without isoniazid, and hydrazidase activity of these cells was followed in the course of cultivation. Enzyme assay method was reported in the preceding paper (Amer. Rev. Resp. Dis. in press) and specific activity was calculated as micromoles of hydrazine formed per hour pergm. of dried weight of cells harvested. Bacillary yield was also measured and expressed by mg. of dried weight of cells harvested from each culture flask containing 40 ml. of the me dium.
Effects of metals on the growth of isoniazid-resistant cells were summarized as follows: (See also Table 1)
1) The addition of metal, with exception of Mg++ and Mo, inhibited the initial growth of the cells, especially in the presence of isoniazid.
2) Growth rate of the cells during constant growth phase was increased by the addition of metal, with exception of Mg++ and Fe+++, in the absence of isoniazid, but in the presence of iso niazid, the addition of metal, except Ca++ and Mo, decreased the growth rate.
3) Maximal yield of the cells was increased by the addition of metal either with or without of isoniazid.
The action of isoniazid on the growth of the resistant cells was affected by the addition of metal as follows and these results were also summarized on the second half of Table 1.
1) Initial growth on the basal medium was inhibited to about two-thirds by the addition of isoniazid, though the cells used were resistant to the drug. The action of isoniazid was enhanc ed by the addition of Mg++, Zn++, Fe++, Mo, and C o++, but not by Mn++. and Fe++.
2) Growth rates of the resistant cells grown on the basal medium and Mg-, Ca-, Fe++ -supplemented media were accelerated by the addition of isoniazid, but on the contrary, isoniazid depressed growth rates of the cells grown on Mn and Co-supplemented media.
3) Maximal yield was not affected by the addition of isoniazid in any case of media. In the preceding paper, the inhibition of hydrazidase by fluoride, borate, 8-hydroxyquinoline and o-phenanthroline, which were known as metal-enzyme inhibitors, was reported. As the results of this inhibition-experiment suggested the possibility that some metal might have an essential roll in enzyme action, several metals were tested as for their effects on hydrazidase production. Results were shown on Figs Most of the metals tested were inhibitory on the enzyme production, when added in excess. But Fe++ and Co++ affected on hydrazidase production in a special way as shown in Figs. 9 and 6, respectively. Especially, it must be noticed that hydrazidase activities were very high at the initial stage of cell growth when they were cultured on the FeoeO-or CooeO-supplemented medium. As for the significance of these metals on the enzyme-production or on the enzyme-action, it is not possible to say something conclusive from such type of experiments, though they are very suggestive, and the problem will be studied further with purified enzyme preparation from other sides.

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Two-hundred-fifty-six patients with pulmonary tuberculosis were divided into 8 groups. These groups were studied using oral administration of INH, IHMS and INHG and parenteral administration of IHMS. In the latter regime IHMS were given intravenously, subcutaneously and by intravenous drip.
(1) Oral administration (a) INH 4mg/kg, IHMS 7.9mg/kg, INHG 10.8mg/kg were given to patients of each 3 groups, checking the concentration of biologically active INH in serum at 2, 4, 6 hours after administration. Mean values of levels of active INH were compared.
The mean level of active INH at 2 hours of the group administered with INH showed the highest of all 3 groups, being 1.13γ/cc and fell rapidly to the levels of 4th hour (0.80γ/cc) and 6th hour (0.33γ/cc). The mean level of active INH at 4 hours of the group administered with IHMS showed the highest (1.05γ/cc), rising from the level of 2 hours (0.97γ/cc) and gradually fell by the 6th hour (0.73γ/cc). This level of the 6th hour showed the highest of any of these 3 groups. It seemed remarkable with IHMS that the level of active INH rose to a peak at 4 hours and gradually fell to the level of the 6th hour. (b) Three other groups were studied using oral dosage of INH 8mg/kg, IHMS 15.8mg/kg and INHG 21.6mg/kg. Levels of active INI-1 at this time were higher than those of 3 groups of (a), but each curve of change of active INH levels of every 2, 4, 6 hours after administration coincided with those of the same drugs of (a).
(2) Parenteral administration. Thirteen cases were studied using 0.5 gr. of IHMS which were administered intravenously, subcutaneously and orally by the same patients. Nine cases were studied using 1.0gr. of IHMS orally and 1.0gr. of IHMS was dissolved in 500cc of normal saline and was given intravenously to the same 9 patients at a rate of ca. 45 drops perminute. The curves of change shown from levels of active INH administered with IHMS orally in these 2 groups were quite alike to those of the oral dosage of IHMS of (1). However, the curves of intravenous and subcutaneous adminis tration of IHMS were quite alike to the curve of oral administration of INH, and the peak of 2 hours fell rapidly to the level of the 6th hour. Levels of active INH by intravenous drip of IHMS by 2nd and 4th hours showed the highest of any of the methods tested.
(3) Under mathematical consideration we found that: it would be the fundamental condition so as to keep active INH level higher at the end of a definite period of time that the drug of definite amount had to be given into blood little by little continuously during the definite period, not to be given at the beginning at once. This seemed to explain precisely our clinical data above mentioned.

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Inorder to study the influence of stress in pulmonary tuberculosis, daily determination of urinary 17-KS and chemocorticoid (17-OH) was carried out on the tuberculous patient, who had hemoptisis.
Urinary total 17-OH determination was carried out with Porter-Silber, Reddy Torii modified method. 17-KS determination was carried out with Zimmerman, Miyake modified method.
Illiberal hemoptisis has no influence upon the evacuation of urinary adreno-cotical hormon. By moderate hemoptisis, the evacuation in creased after temporary decrease.
By intensive hemoptisis, the evacuation showed a low value.

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Resistances of tubercle bacilli occurring in patients to alpha-ethyl-thioisonicotinamide (1314 Th) and thiosemicarbazone were determined by a direct method of the drug resistance test.
Natural resistance to 1314Th was not always accompanied by thiosemicarbazone resistance and there was only a random relationship between natural 1314Th resistance and thiosemicarbazone resistance. On the other hand, acquired resist ance to 1314Th was mostly accompanied by an increase of thiosemicarbazone resistance, although the latter drug was never administered. Thus, there exists an in vivo one-way cross resistance relationship between 1314Th and thio semicarbazone.
Natural resistance to 1314Th was thought to differ from the acquired resistance to 1314Th in the origin and nature of resistance.

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