1. The biologically active plasma levels of INH after the oral administration of 4 mg/kg of INH were determined by means of the Vertical Diffusion method, and classified on the following criteria:
6 hour level
Rapid Inactivator (R):
Equal to or less than O.15 mcg/ml
Intermediate Inactivator (I):
Between O.15 and 0.8 mcg/ml
Slow Inactivator (S):
Equal to or more than 0.8 mcg/ml
2. The amount of free isoniazid excreted i n urine measured by the Hughe's Method increases in the order of R, I and S. (Table 1 & 2, and Fig.1, 2, 3 & 4) If we express three groups of metabolites excreted in 6 hour urine in percentage, the amounts of free INH and hydrazone are the largest in slow inactivators, showing that slow inactivators can not acetylate INH to the full extent and are obliged to compensate the insufficient acetylation by the increased formation of hydrazone. (Fig.5)
3. The simultaneous determination of the biologically active INH in blood plasma and the free INH in urine reveals that there is a direct but not very close correlation between them. (Table 3, and Fig.6 & 7) The average values of the percentages of the free INH in 6 hour urine for rapid, intermediate and slow inactivators are 9.08, 10.92 and 18.56 respectively. But it does not seem possible to have the same classification of rapid, intermediate and slow inactivators on the basis of urine analysis as on the 6 hour blood level.
4. The influence of the increased doses of INH upon the biologically active INH blood levels in rapid inactivators in the case of Japanese is less remarkable than in the Caucasians, but more marked than in the Esquimos. (Fig.8 & 9) If the test doses are raised, both free and acetyl INH in urine increase to some extent, but the increase of hydrazone is the most remarkable, and if we express the relative amount of respective metabolites in percentage, free INH remains almost unchanged, acetyle INH decreases and hydrozone increases markedly. (Fig.10)Hydrozone seems to play a role of buffer also under these circumstances.
5. The relationship between the concentration of the free sulfonamide in blood plasma 9 hours after the oral dose of 1g of sulfisoxazole measured by means of Bratton-Marshall's technique and the biologically active blood level of INH 4 hours after the administration of INH is demonstrated to a certain extent. (Table 3 & 4, and Fig.11, 12, 13& 14)

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Polisobronchography is a procedure in which routine bronchography is doubly-taken in a deep inspiration phase and in a deep expiration phase, one after the other, on the same sheet of X-ray film.
Swallowing movement was stopped during the polisobronchography in order to avoid the possible influence on the respiratory changes of trachea and bronchi. By using this polisobronchography, the author measured the changes of the inside diameter of trachea and bronchi, the changes of the angle of main bronchi, and the displacement of bifurcation as well as peripheral bronchi during deep respiration on healthy persons.

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During a long period of one year and a half we have repeatedly isolated from the sputum of a patient who was treated as pulmonary tuberculosis a large quantity of bacilli which may be considered to be the so-called unclassified mycobacteria (nonphotochromogen).
This acid-fast bacillus showed one or two bacteriological properties similar to those of mycobacterium tuberculosis, but it chiefly resembled to the saprophytic acid-bacillus in the natural world and its pathogenicity was slight for mice and almost negative for other animals such as guinea pigs, rabbits and hens.
In order to diagnose the disease as a case caused by unclassified mycobacteria it is necessary that the increase and decrease of the bacteria should be closely connected with its clinical course. Indeed, our patient's discharging of acid-fast bacteria was parallel to his roentgengram and it became negative as his cavity disappeared.
Although thcre is much left to be discussed about the origin or classification of unclassified mycobacteria, we understand our case indicates the possibility of the so-called unclassified mycobacteria's causing the lesions in lungs.
Most of the cases so far reported as being caused by unclassified mycobacteria are serious ones, but if unclassified mycobacteria are to cause primary Pulmonary lesions, it may be inferred from out experimental cases that unclassified mycobacterial may be seen in slight cases rather than in serious ones.

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It has been report ed by many investigators that the virulence of the INH-resistant, catalase negative strain of tubercle bacilli for guinea pigs is attenuated. However, in our previous experiment with guinea pigs, the degree of this attenuation was less obvious when examined by airborne infection than when other infection routes were employed. In that study, observations were made only up to 8weeks after the infection. In the present study, the observation period was extended up to 50 weeks after the infection.

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Our knowledge concerning the atypical (also designated the “Anonymous” or the “Unclassified”)mycobacteria has increased considerably during the last 10 years in Japan. We had a clinical impression that these atypical mycobacteria might be more frequent in patients with complicated pneumoconiosis. All of the cases upon which this report is based have come to our attention because they were suspected of having tuberculosis or pneumoconiosis. Our case-identification procedure has been the isolation of atypical mycobacteria from routine specimen examined for M. tuberculosis. In the present report the terms “infection” and “case” mean simply that atypical acid-fast bacilli have been cultured three or more times from the sputum or resected lung lesion.

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The action of isoniazid on tubercle bacilli and the mechanism of the isoniazid-resistance in mycobacteria were studied with ¹⁴C-labelled isoniazid. The drug-sensitive, parent H37Rv strain of Mycobacterium tuberculosis and its mutant strain resistant to 50 mcg/ml of isoniazid were cultivated in a synthetic, liquid medium containing Tween 80 for 10 to 28 days at 37°C. The cells of tubercle bacilli were centrifuged and washed thrice with phosphate buffer. These cells were resuspended in phosphate buffer and ¹⁴C-isoniazid was added to the suspension to give the concentration of 1 to 5 mcg/ml. After the incubation at 5° or 37°C for 24 hours, the cells were washed thoroughly with saline containing Tween 80, placed on sample dishes and counted with a gas flow counter.
Results obtained were as follows, the isoniazidresistant Hs7Rv-RINH strain bound less amount of isoniazid than the sensitive H₃₇Rv strain did; the amount of isoniazid bound by the sensitive strain reached maximum at the 6th hour of incubation, whereas isoniazid absorbed by the resistant strain did not differ in amount throughout the first 24th hours of incubation; the isoniazid-sensitive strain bound more amount of isoniazid at 37°C than at 5°C, whereas the resistant strain absorbed the same amount of isoniazid either at 37°C or at 5°C.
In the sensitive strain, cells harvested from a young culture bound more amount of isoniazid than the cells havested from an old culture, whereas in the resistant strain, no difference was observed in the amount of isoniazid absorbed the cells from an old culture and those from a young culture. These results suggested that the binding of isoniazid by the resistant strain would be due to the non specific absorption having no relation to the metabolic activity of the cells. On the other hand, the sensitive strain was observed to bind a larger amount of isoniazid taken up by the metabolic activity of the cells.

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