In an attempt to study brochial hypersensitivity for chemical mediator substances, graded doses of acetylcholine and histamine have been administered daily for 7 days by inhatalion to guinea pigs and occurrence of experimental asthma was assessed. The guinea pigs were divided into 5 groups depending on the experimental procedures. a) Animals received graded doses of acetylcholine daily for 8 days (short term experiment). b) Animals received graded doses of acetylcholine every 4 day for one month (long term experiment). c) Animals received graded doses of histamine daily for 8 days (short term experiment). d) Animals received graded doses of histamine every 4 day for one month (long term experiment). e) Animals without any treatment. Although there is a individual variation as well as day to day vatiation, the data indicated that bronchial hypersensitivity threshold for acetylcholine was ranged from 200 to 10, 000, the average being about 4, 000 in short term experiment. It ranged from 500 to 30, 000, the average being 4, 000 in long term experiment. The threshold for histamine ranged from 200 to 2, 000, the average being about 600 in short term experiment. In long term experiment, the threshold for histamine ranged from 200 to 10, 000, the average being 1, 300. Since these two drags fail to produce experimental asthma in other animals, since both drugs can cause experimental asthma in man and guinea pigs, it is suggested that the mechanism whereby asthma can be produced might be closely resembled in man and guinea pigs. Although the over all findings in our present experiment support the view that hypersensitivity threshold to acetylcholine and histamine is low in asthematic patients as well as in the guinea pig, our detailed and continuous evaluation furthere added the evidence that some of the guinea pig high threshold for these 2 drugs comparable to those of some asthmatic patients who have high threshold for acetylcholine and histamine. Reflactory elevation of threshold reported can be explained in the basis of day to day variations observed in this experiment.

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Recently we came acquinted with the fact that symptoms of inhalative asthma are rather fraquently found among people who are engaged in manufacturing wooden wares in the suburbs of Hiroshima City. And the followings are the results of our researches concerning their causes. 1) In the patients of this asthma, the reversible decrease of one second vital capacity ratio was found only while the symptoms were positive, and the leucocytic eosinophilia was found concerning the diffe-rential count. 2) Positivity was found in all the following tests: that is, the skin test, the conjunctival test, Prausnitz-Kustner's reaction and sensitized haemagglutination reaction by way of the allergen extract of clethra barbinervis. 3) By applying the treatment with specific desensitization by way of the clethra barbinervis, the outbreak of inhalative asthma could be prevented. 4) In the contrastive cases of healthy people or the patients with ordinary bronchial asthma, the result of the skin test by way of the allergen extract of clethra brabinervis were all negative. On the other hand, when the skin test was applied to the workers in the lumber mill who are not dealing with the clethra barbinervis, three cases were found who are positive to the allergen extract of clethra barbinervis. Concerning these three, all of them had experience in former days of dealing with the clethra barbinervis, and two among them were positive to the Prausnitz-Kustner's reaction and the remaining one is said to have shown a symptom something like allergic rhinitis when he was dealing with the clethra barbinervis. 5) In order to prevent the outbreak of this kind of asthma we advised them to equip the mill with dust collectors. These are the report concerning the symptoms of inhalative asthma or allergic rhinitis which is seen in people working in the lumber mil, and it is expected that this may contribute to awaken some interest and attention towards the existence of the similar asthma.

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A group of 12 female rats (Wistar King A) were thymectomized within 24 hours after birth and another group (10 sham thymectomized) were handled in the identical fashion except that the thymus was left in situ. Each of the animals received a suspension of heat killed tubercle bacilli (0.3 mg) in mineral oil (Drackeol 0.1 ml) in the left hind footpads. The following results were obtained. 1) In the incidence of the adjuvant disease, there was no significant difference between the thymectomized and the sham thymectomized group. 2) In the mean average days of onset and severity of local lesions induced at the injection site, there was no difference between the groups. 3) The lesions other than the local ones were milder and 5 to 7 days later in onset in the thymecomized group than in the sham thymectomized. These findings suggest that the local lesions were caused primarily by the toxic effect of the adjuvant while those induced at other sites probably by the secondary effect of the adjuvant were dependent upon some immunologic reactions related to the thymic function.

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A case with bronchial asthma is reported, who presented the symptoms of hypersensitivity directly after the intramuscular injection of ACTH. A.O., a housewife 25 years of age, was admitted to our hospital because of bronchial asthma. On the occasion of eosinophilolysis test (Thorn's test), after the intramuscular injection of 25 units of ACTH, the urticaria-like eruption with remarkable itch was manifested in almost all over the body. She shed much tears, and her lips became edematous. The patient complained of uncomfort in the pharynx, and presently of dyspnea. The lowering of blood pressure was observed, but syncope did not come. To the intracutaneous test by ACTH solution (dilution of 0.1, 0.01, 0.001, 0.0001, 0.00001 unit/ml), positive reaction was proved. And the Prausnitz-Kustner's passive transfer test by ACTH solution (dilution of 0.1 unit/ml) showed positive raection, too. From the results of these examinations, it is considered that the above-mentioned side-effects by ACTH injection are attributable to the hypersensitivity to ACTH. Judging from the latest literatures available on this subject, the intracutaneous test before ACTH injection is clinically recommended.

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The interaction of bovine trypsin with its rabbit antibody was investigated in vitro and the following results were obtained. a) No change was observed in the antigenicity of trypsin in quantitative precipitin reaction even after its enzymatic active site had been masked with the suitable reagents. It was presumed in this respect that the enzymatic active site of trypsin molecule were no antigenicity. b) Specific inhibition of anti-trypsin antibody on the proteolytic activity of trypsin was demonstrated using casein as the substrate. On the other hand, almost no inhibition was observed when the small-molecule substrate (Benzoyl Argininamide) was used instead of casein and, accordingly, the inhibition mechanism was presumed to be steric hindrance. c) It was established that rabbit antibody r-blobulin was hydrolyzed by traypsin into mono valency antibody fragments in the presence of cysteine. These fragments showed the same properties as the papaindigestion fragments (FI, FII) in many respects. The ″FIII″fragment was not found in the digestion mixture. d) It was also established that anti-trypsin antibody was hydrolyzed by its antigen itself. That is, the ″antodigestion″of the trypsin-antitrypsin immune precipitate was observed under the suitable condition and the reaction mixture contained the digested antibody fragments.

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The authors reviewed a series of serological studies carried out by their cowerkers employing somatic substances of the tubercle bacillus as antigens. These studies were performed on some technical basis elaborated by them. Firstly, proteins isolated from mechanically disintegrated bacillary cells with minimum denaturation were proved to be highly active serologically and were used for the titration of corresponding humoral reactivities, in addition to well-recognized bacilary antigens-phosphatides and poly-saccharides which were also obtained mechanically more effectively than from intact cells. Secondly, titration of precipitins against the three bacillary antigens were performed by the agglutination reactions of antigen-coated collodion particles established by them. The techniques are delicate enough to estimate relative concentration of these precipitins in tberculous sera. From the data of comparative titrations of precipitins and complement fixing properties in sera from patients with pulmonary tuberculosis, it was indicated that humoral reactivities ageinst the proteins were more plentiful and of more significance than those against other bacillary antigens. Therefore, data obtained by the use of proteins were chiefly described in this paper. Complement fixation titer as titrated against the proteins or phosphatides kept a certain parallelism with severity of the pulmonary disease. In fact, complement fixation using the proteins was useful in making differential diagnosis of chest shadows resembling tuberculosis and in speculating prognosis of tuberculosis. On the contrary, precipitins to combine with the proteins or phosphatides as measured not only by the agglutination, above mentioned, but also by less sensitive flocculation gave quite inconsistent results with complement fixing properties against these bacillary antigens. It was noteworthy that antiproteins were distinctly of low titer (1/10 or so) in relapsing or severe cases of pulmonary tuberculosis, whereas the same precipitins were plentiful (1/80-1/160) in cases fighting successfully in the face of advanced disease. It was known, therefore, that high concentration of the antiproteins could be taken as a serological sign of powerful operation of resistance of the host against the invader. It was noticed, however, that clinical value could not be attached directly to the antiprotein titer, because it was commonly low in severe and almost recovered cases as well as in healthy positive reactors to tuberculin. On this, some attempt was undertaken in order to attach clinical value to the titer. It was demonstrated that the antiprotein titer would provide a valuable index of the balance of activities between the host and the invader, when it was sutdied incombination with complement fixation titer or erythrocyte sedimentation rate. For example, ration of antiprotein strength to E.S.R. (reciprocals of antiprotein titer/E.S.R.) was large reaching 6.0 or more not only with improving and almost recovered cases but also with healthy positive reactors, contrary to severe cases with which the same ration was inevitably small (0.2 or so). Likewise, ration of antiproteins to complement fexing properties was found to bear analogous clinical significance. It may be of utomost interest that the antiproteins are scant in severe patients, while the well-known Middlebrook-Dubos antibodies (precipitins) are not so. It was suggested that on some experimental evidences that production of precipitins against toxic bacillary substances as proteins would be paralyzed in severe clinical condition, whereas production of precipitins against non-toxic substances such as lipo-polysaccharides active in the Middlebrook-Dubos hemagglugination, would not be inhibited even in the mostly hopeless condition.

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