In 1965, Hilson claimed the successful transmission of M. leprae into the foot-pad of the white wistar rat. Therefore, we have performed examinations on the multiplication of M. leprae in the hind foot-pads of rats, using materials (M. leprae) of 3 mouse-passages.
Furthermore, we have performed a comparison of the differences in the multiplication rate between rats and mice, and the enhancing effects of cortisone-administration or thymectomy in rats.
White wistar rats were used, and the technics of inoculation and thymectomy were similar to those described by ourselves, as reported elsewhere. The cortisone was intramusculary injected into their hind paws at a daily dosage of 8mg., which administration was continued for 6 days, in the second week after inoculation with M. leprae.
The inoculum was 5.8×10³ bacilli (Fukuzato), 6.4×10³ bacilli (Fujii) and 9.7×10³ (SH-2=N-2401 p₁₂ passage strain isolated by C.C. Shepard) per each foot-pad.
The details are shown in Table 1. In the case of mice, the bacillary counts of M. leprae in each foot-pad rose to a plateau level of at most 10⁶, but in the case of rats it rose to a plateau level of at most 5.0×10⁴-10⁵. The second passage (rat to mouse) examined at 25 weeks after transmission from the first passage in rats showed the bacillary counts of M. leprae similar to that of the first passage in the mice. No growth was observed on Ogawa's medium, and inoculation with M. lepraemurium in the rat foot-pad produced a slighter nodular swelling of the injected foot-pad than that of the mouse footpad. In addition, in the cortisone-administered rat and thymectomized rat the bacillary count did not rise to a plateau level at an early stage after inoculation, the results being different from those of the mouse and hamster, as described elsewhere by ourselves.
In summary, it can be said that we have observed the successful transmission of M. leprae into the hind foo-pad of the wistar rat, but the susceptibility of this animal to M. leprae was less than that of the mouse, as shown by the bacillary count and microcolony of M. leprae in the foot-pad.

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Today, the studies of murine leprosy and the murine leprosy bacillus still maintain an important place as a model in the study of leprosy.
From the finding that when mice are inoculated with the leprosy bacillus, the organism, which proliferates, replaces the murine leprosy bacillus, a study was made of latent murine leprosy bacillus in the mouse and the contamination of various experimental animals by acid-fast organisms, and a new method of investigation utilizing spread smear preparations of subcutaneous connective tissue was devised. The attempt was made to clarify the range of contamination of experimental animals by the murine leprosy bacillus and other acid-fast organisms, and from the results, point out the precautions which must be taken in conducting animal experiments with the leprosy bacillus. The effort was also made to broaden the knowledge regarding murine leprosy in members of the murine family other than the rat (rattus norvegics norvegics, rattus rattus alexandrinus, rattus rattus rattus).
The animals investigated were the mouse, hamster, wild members of the murine family, guinea pig, rabbit, cat and monkey.
The following conclusions were reached.
1) Special caution should be exercised in conducting experiments on the animal transmission of the leprosy bacillus, especially latency of murine leprosy bacillus.
2) The finding that the latent murine leprosy bacillus is present not only in the rattus family but also in the mouse and wild muridae, supplements the report of Nishimura (1938) on the category of murine leprosy.
3) The results suggest that the belief that natural murine leprosy infection takes place by direct contact, must be revised.
4) It can be said that the finding that the skin of healthy experimental animals is contaminated by acid-fast organism affords some understanding of the yet unclarified natural phenomenon.

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チオザミン(P-(P'-Aminobenzene sulfonyl)-benzal-dehyde thiosemicarbazone)の薬理作用ならびに臨床効果,および抗菌作用等またこれが合成法等についてはすでに報告した。
本論文においては抗酸菌の一つであるBCG菌を用いて,チオザミンの各濃度による影響を吸光度計を用いて検討した。先に報告したH37Rvと同様に弱いながらも抗菌作用のあることを認めた。そしてそれは濃度に比例する。
次に鼠らい発症におよぼす影響について検討した。この場合コントロールとして比較的鼠らい発症を抑制するとされているINAHを用いた。また同時に当園の研究で一応らいの臨床に有効とされたアセタミン,DOT,PBS-2をも用いた。これらを6日間餌に混じて経口投与し,マウスの鼠らい発症ならびに結節の拡大を15日間隔で9日間測定した。その結果,チオザミンの効果が比較的良好であつた。
次にこれが作用機序の一端を追究する目的を以てBCG菌の呼吸系におよぼす影響をワールブルグ検圧計を用いて検討した。その結果わずかながらBCG菌の呼吸を抑制することを知つた。さらにBCG菌のタンパク生合成におよぼす影響を放射性アミノ酸のタンパクへのとりこみについて放射能測定によつて検討し,その結果は特に影響はなかつた。
またBCGのリボゾームにおよぼす影響を検討したが同様その効果はなかつた。薬理学的検討の結果は本化合物は毒性少なく,比較的安全な薬物であることを知つた。

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先に著者はDDSの生体内変化に関する研究において,そのアセチル化体が生体内において相互に移行することを報告した。チオザミンも化学構造の類似性から同様アチル化体の形成が予測され,また芳香核の-NH₂基のN-グルクロナイドの形成,N-スルフオナートの生成,チオ尿素部のN-アセチル化などが考えられる。
そのほかSの離脱,芳香核の-〇H導入も可能性がある。
まずチオザミン投与後のウサギ尿について排泄されるグルクロン酸を定量した。その結果はN-グルクロナイドはほとんど無く,極めて微量で主代謝物とは考え難い。
ウサギ尿(チオザミン経口投与の)についてのペーパークロマトの結果は未変化物を認めた以外には主代謝物のスポットは認められなかった。よってチオザミン投与のウサギ尿を塩化メチレンで連続抽出を行い,溶媒を溜去して残査を少量の塩化メチレンで溶解し,アルミナカラムで分画して,それの分画物をペーパークロマトで展開し,紫外線照射によって同様な色調スポットを探してそのRfを求めた。そしてそのRf価を示す部分を切取り,メタノールで抽出した。予想されるチオザミンのトリアセチル化体とモノアセチル化体を合成して,これと薄層クロマトで同定し,モノアセチル化体が主代謝物であろうことを推測した。

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An aqueous suspension of M. lepraemurium (Hawaiian strain), prepared from the organs of mice previously inoculated with this bacillus before a long period of time, was inoculated intravenously and subcutaneously into the mice of ddN strains. These mice were killed and autopsied from time to time. The removed organs, lymph nodes and subcutaneous nodules were ground in the mortar. The most part of ground materials was inoculated onto the 1% egg yolk medium principally and also onto 3% Ogawa's egg media and 1% Ogawa's egg media. These media were incubated at 37°C for nearly 3 months. The reading was assumed positive when the colony-like products were observed macroscopically.
The following was the results: The material which showed most abundant growth of bacilli in the mice during 5-8 months, gives positive result in 14 cases of 22 (63.8%) using 1% egg yolk media, while only one positive case out of 4 using 3% Ogawa's egg media. No positive case was found in 1% Ogawa's egg media. The colony-like products appeared to be a R-Type with somewhat moist nature and showed a very thin yellowish tint. We have succeeded so far in obtaining four successive cultures. The growth was very slow and almost took 2-3 months until the definite growth was assured. A smear specimen displayed well-stained acid-fast bacilli, among them also many elongated ones. These bacilli grew only at 37°C but failed to grow either at 22°C or 45°C. Reproduction test of these bacilli to the mice was favorable. Such a property is identical in every isolated bacilli.

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