From the immunological standpoints, we have examined Ag-Ab reaction in the gastric mucosa of experimental animals, using BSA as Ag, anti-BSA rabbit serum as Ab, and Pontamine Sky Blue as indicator. 1) Applying the technique of "Passive Cutaneous Anaphylaxis" (PCA), we obtained the interesting results which might be called "Passive Mucosal Anaphylaxis" (PMA), that is PCA in the gastric mucosa of guinea pig and dog. 2) After the soluble Ag-Ab complex was injected in the gastric mucosa, there observed the formation of erosion or ulcer within two hours. Histologically, chief cells of stomach were almost destroyed in the reaction area, whereas some of parietal cells were still remained. Marked cell-infiltrations were also observed in the destroyed gastric mucosa and around the small vessels in the submucosa. 3) After fixation of Ab in the gastric mucosa by injection directly to the mucosa, Ag was given orally. Two to six hours later, obvious leakage of dye was observed in the injected area of Ab. This mean the increase of vascular permeability by Ag-Ab reaction. In Ag-Ab reaction, complement components in serum participate with such phenomena as cell damage, increase of vascular permeability and cell infiltration, which might be explained by the mechanism of immune cytolysis, vasolysis and cell infiltration. Although many investigators have reported on Ag-Ab reaction in gastric mucosa, these reactions are so complicated with many modifiers, that it is difficult to recognize weather these reactions are really caused by Ag-Ab reactions themselves. To avoid the complexity, we have performed model experiments under purified Ag-Ab system. Thereafter, these experiments throw some lights on the immunological nature in the course of digestive diseases.

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In 1960, the tuberculin active peptide (TAP yamamura) was prepared by Yamamura from cells of M. tuberculosis and proved by Someya to have no sensitizing effect, when injected into guinea pigs with adjuvant. In the present experiment, an attempt was made to test the influence of repeated TAP injections. 1) Old tuberculin and 0.25 mcg of TAP were injected respectively, at two sites on the backs of five adults. After one month old tuberculin and TAP were injected at four previously injected sites and at two new sites after the manner of the preceeding experiment with PPD and CF. Reactions were observed as previous reports. At all four sites where injection was repeated, early reaction and accelerated reaction were observed in contrast to the new sites. 2) Three adults were given TAP injection at the new site a the left upper arm, and also given tuberculin injetion at the new site on the right upper arm. Thereafter, every one to two months, TAP and tuberculin were injected at the same sites respectively. Injections were repeated three times. Reactions were observed 4, 24, 48 hours after injection. In the first test, no early reactions were observed on both sides, and intensity of reaction increased as time elapsed. In the second test on both sides remarkable erythema and induration appeared after four hours. The reaction attained their maximum intensity after 24 hours. In the third and fourth tests on both sides, the early reaction were nearly the same as in the second test, while the intensity of the delayed reaction after 24 to 48 hours decreased in accordance with the repetition of the injection. The reaction pattern against TAP was almost the same as against tuberculin. In summary, the injection of TAP also influenced the subsequent tuberculin reaction at the same site. Between old tuberculin and TAP no significant difference was observed in the effect of modifying the subsequent tuberculin reactions.

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Anti-allergic effects of quinoline derivatives (quinine and chloroquine) and pyrazolone derivatives (phenylbutazone, aminopyrin and sulpyrin) were examined against passive cutaneous and systemeic anaphylaxis (PCA and PSA respectively) in guinea pigs. Also the inhibitory effects of these drugs against histamine injected intradermally or intravenously were compared. Quinoline derivatives exerted an equal inhibitory effect upon PCA and upon the increased vascular permeability caused by histamine. On the other hand, phenylbutazone and aminopyrin inhibited PCA more intensely. This mode of action is in a reversed relationship to that of antihistaminics which are strong inhibitors to histamine but are almost inert to PCA. However, sulpyrin did not inhibit PCA and histamine at all even at the high dosage of 200 mg/kg. Contrary to the cutaneous reactions, each of quinine, chloroquine, phenylbutzzone and aminopyrin inhibited neither PSA nor histamihe shock, though antihistaminics protected the animals from these shocks at a small dosage of 5 mg/kg. On the basis of such characgeristics of the modes of action of these drugs, some discussion was made upon the difference between the mechanisms of PCA and PSA.

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During the period of the recent endemy of influenza in Japan the author tried to immunize the mother under gestation positively with Influenza-Adjuvant-Vaccine in anticipating also to bestow the immunization to the fetus. 0.1 ml of Infiuenza-Adjuvant-Vaccine was injected intramuscularly in 59 cases of pregnant women in a range of beginnings of 7th to 9th gestational month. Before the vaccination the maternal blood was taken and after the vaccination, at the delivery, the maternal bloods as well as the umbilical cord blood was taken. As the control, in 33 case, also the maternal blood as well as the umbilical cord blood was taken likewise and the antibody titers for 7 strains, namely, A-Swine, A-PR8, A1, A2, B-Lee, B-Setagaya and B-Taiwan were measured by means of the agglutination inhibition test. The results obtained were as follows. 1) On an average, in 20-40% of 92 cases composed of the maternal blood taken before the vaccination and the nonvaccinated maternal blood taken at the delivery, the antibody titers were above 32 for Type A and B, particularly for B-Setagaya strain. On the other hand, the umbilical cord blood in the control group with titers above 32 was observed only in 11.9% of them. 2) In the vaccinated group, the maternal blood at the delivery had the titers above 32 in 64.8% for Type A, 93.2% for Type B and 79.0% on an average. The umbilical cord blood revealed the titers above 32 in 57.4% for Type A, 72.7% for Type B and 65.1% on an average, which showed the conspicuous elevation of the titers of the umbilical cord blood due to the maternal vaccination. 3) The antibody titers of the umbilical cord blood were changed almost in parallel with the fluctuation of the titers of the maternal blood but in general the titers were in low levels except some cases (9.6%) in which they were almost of the same levels as in the mother or higher. 4) In no case, any side effecl of the vaccination such as premature birth, intrauterine fetal death or malformations and etc. was observed. 5) The elevation of the titers does not always mean clinically the increase of the defense potential against the infection of the influenze but the increase of the titers of the umbilical cord blood is apparently significant for the increase of the defense potential against the infection.

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Guinea-pigs were passively sensitized with anti-egg-albumin rabbit-serum and shocked with intravenous injection of the allergen. 5-hydroxytryptophan (5-HTP) decarboxylase was extracted from kidney and liver by ammonium sulfate fractionation and purified by absorption of alumina Cγ. 5-HTP was incubated with purified 5-HTP decarboyxlase, pyridoxal phosphate and other drugs in vitro at 37℃ for 1-2 hr and the amount of increased serotonin was estimated by spectrophotoflurometric assay. The auther studied on LSD monohydrate as anti-serotonin drug, cyproheptadin, diphenylpyraline as anti-allergic drugs, and the influence of 5-HTP and 5-HTP decarboxylase activity and the following results were obtained. 1) The activity of forming serotonin by 5-HTP decarboyxlase extracted from kidney of normal guinea pigs was more powerful than that extracted from liver. 2) The activity of 5-HTP decarboxylase was remarkabely inhibited by LSD-monohydrate, but not a significant effect was observed by other drugs tested. 3) Pyridoxal phosphate used in the test as acoenzyme showed only a slight effect to anti-allergy drugs. 4) The activity of serotonin (5-HT) was found to be destructed by several anti-allergy drugs and the destruction percentage was 25% in the case of cyproheptadine, 20% in diphenylpyraline and 5% in LSD.

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Fundermental studies of intradermal reaction in the immediate type were carried out upon asthmatic patients, carriers of parasitic diseases and also normal subjects; 1376 persons in total. 1) The distribution of wheal diameter due to injection of antigen solution shows of bimodal charactor in general which is considered as a mixture of two different normal distributions from statistical view point. Accordingly, the distributions of wheal due to the antigen of Dirofilaria immitis gained from the mass survey of 1110 inhabitants in an endemic area were critisized per different age groups statistically, and the results show that the boundary between positive and negative reactions designed as 9 mm indicates to include 10% of the error determining the positive responce as negative tor vice versa. When the reactions less than 9 mm in wheal and more than 20 mm in erythema are adopted as positive, such reactions occupy 14% of whole positive reactions, and lost positive reactions shall be included in this cathegory. 2) The main cause of wheal and flare formation is considered as the reaction against the mobilized histamine due to the antigen-antibody complex in tissue. Accordingly, the size of reaction is much influenced by the different sensitivity to histamine per each person. And quantitative difference of antigen antibody complex is considered as less influence to wheal and flare formation. 3) There is a threshold value of positive skin reaction when a series of two fold dilutions of antigen is performed on the same subject. This value represents roughly the skin-sensitizing antibody titer. The formation of blocking antibody due to the hyposensitization therapy changes the threshold value toward hyposensitivity. This value decreases markedly, when the reagin formation is considered as decreased; for instance, the complete discarding of parasites from the carrier.

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Recently the comercial allergen extracts for scratch tests become available in Japan. Using these allergens (made by the Torii Co. in Japan) as well as American allergen extracts (made by the Hollister-Stier Co.), we have investigated several points concerning scratch tests. Two hundred seventy-five children with bronchial asthma are 117 healthy nonallergic children of one primary school were used. The following results were obtained. 1) There was no statistical difference of reactivities to the allergic and non-allergic children between Japanese and American house dust extracts. 2) The rates of positive reactions to house dust extracts on the asthmatic children older than 5 years of age were statistically higher than those of infants with dermal and/or respiratory allergy. 3) The percentages of positive reaction, with intensity above 2+to Japanese allergen extracts, except house dust extract, on the asthmatic children were 4 to 21%, while those on the 117 healthy children were 0 to 4 per cent. 4) The relative accuracy of scratch tests of several kinds of foods (egg, milk, pork, salmon and peanut) to clinical allergy was estimated as being 20-40%. 5) The antigenicity of American house dust extract was well preserved as long as 2 to 3 years, provided it was kept under refrigeration while not in use for testing. 6) In 9 children with bronchial asthma the intensity of reaction of scratch tests to the same lot of several allergens have varied significantly while that of house dust remainded constantly on the same degree when these allergen extracts have been applied 3 to 5 times at intervals of 2 to 7 days or 2 to 12 months. 7) Epinephrine, ephedrine and antihistamines interfered with the reactivity of scratch tests for as long as 6 to 18 hours after their administration.

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Skin test with benzylpenicilloyl-human serum albumin (BPO-HSA) in 2242 patients hospitalized for unrelated conditions yielded positive results in 66 patients, 2.9 per cent. The incidence of positive responses was higher in patients with allergic reactions to penicillin than in patients with no history of penicillin allergy. The test material, therefore, seemed to be a reliable agent for the diagnosis of penicillin hypersensitivity. Forty-six patients who gave positive reactions to BPO-HSA were further skin tested simultaneously with 14 kinds of test materials; Penicillin G, BPO-S-aminocaproate, BPO-hexamethylenediamine BPO_2-HMD), polyvalent BPO-L-polylysine, several kinds of penicilloyl haptens of synthetic penicillin and so on. Mean diameters of wheal reactions to each of these test materials were evaluated by factor analysis. Although the BPO group was found to be the major antigenic determinant, at least other five factors which were almost independent on each other and characterized by different antibody specificity were also detected in these BPO reactive patients. In other words, human anti-penicilloyl antibody was shown to be quite heterogenous and a variety of combinations of antibody specificities were observed in the majority of BPO reactive patients. The combing sites of these heterogenous antibodies were specifically adapted to one of the following antigenic determinants; (1) phenylacetylglycine, the acyl side chain portion of the BPO molecule, (2) 6-aminopenicillanic acid, (3) the penicilloyl molecule of synthetic penicillins, (4) divalent BPO hapten (BPO_2-HMD) and polyvalent BPO hapten (BPO_<345>-Lpolylysine) and (5) the whole benzylpenicilloyl molecule. Evidence was also presented which indicates that divalent BPO-hapten was much inferior to the polyvalent in its ability of histamine rlease in vitro, while the former was as strongly antigenic as the later in its ability to evoke cutaneous responses and Prausnitz-Kustner reactions. Furthermore, it seems noteworthy that two of the three patients who had a positive reaction to penicillin G had a history of immediate systemic, or anaphylactic, allergic reactions to penicillin. From these findings as well as the results of factor analysis, it seems likely that an antibody responsible for this type of penicillin allergy may be different from anti-penicilloyl antibodies.

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