One hundred and ninety one asthmatic patients were treated with menaquinone for over one year and labolatory studies on the mechanism of pharmacologic action of the compound were performed. The results thus obtained are sumarized as follows: 1) Both menaquinone alone and the combined therapy of menaquinone and hyposensitization were considerably effective, but the combined therapy was more effective. 2) In the evaluation on the clinical effect of menaquinone by the double blind method, out of 37 cases with menaquinone, 24 cases (64.9%) were improved, and the placebo effect was recognized only in 26.9% asthmatic patients. 3) Menaquinone inhibited significantly the degranuration of rat mesenteric mast cells in both passive and active sensitization by reagin-like antibody. 4) In a basophil degranulation test of asthmatic patients, the appearance rate of A form basophils was significantly suppressed by addition of goat anti-serum to human IgE in asthmatic patients given prolonged treatment of menaquinone than in controls, but not so much suppressed by addition of menaquinone in vitro.

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The distribution of IgE in cutaneous lesion in patients with atopic dermatitis and with eczematous dermatitis and healthy controls was studied by immunofluorescent technique. IgE-staining cells were detected in the upper and middle dermis in the skin of all subjects examined. They showed typical appearances of mast cells after counter-staining with toluidine blue. The number of IgE-staining cells was increased in patients with atopic dermatitis as well as chronic eczematous dermatitis and was correlated with the intensity of fluorescence. There was no correlation between serum IgE levels and the number of IgE-staining cells. The proportion of IgE-staining cells in total mast cells has been calculated. The average percentage of IgE-staining cells was 54.2% in atopic dermatitis, 41.2% in chronic dermatitis, 29.6% in acute dermatitis and 18.9% in healthy controls. These findings suggest that chronic tissue damage might be a factor initiating antibody's escape from the vessels and its consequent absorption onto mast cells.

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2, 4-dinitrophenyl hapten, when coupled to Salmonella chleraesuis bacilli, was capable of inducing sequential IgM and IgG anti-hapten antibody response in the mouse, both of which were found to be totally thymus-independent. This was demonstrated by the following results: 1) Neonatal thymectomy did not reduce the numbers of hapten-specific direct and indirect plaque forming cells (DPFC and IPFC) induced upon a single intraperitoneal injection of DNP-Salm in their spleens. 2) Neonatally thymectomized animals produced a typical secondary antibody response by two spaced immunizations with DNP-Salm. 3) Reconstitution of lethally x-irradiated mice by only bone marrow cells could restore the hapten-specific PFC response without supplementation of thymocytes. 4) Anti-DNP secondary PFC response was induced in x-irradiated mice reconstituted with spleen cells that had been treated in vitro with AKR anti-C3Hθ antiserum and complement. Furthermore, the anti-DNP antibody response appeared to be initiated by direct interaction of DNP-specific antibody forming cell precursor (B cell) with DNP determinants as evidenced by inhibition of the response by passively administered anti-DNP antibody but not with anti-carrier (anti-Salmonella) antibody. Preimmunization with the hapten on a heterologous carrier (DNP-HGG) prepared animals to produce hapten-specific secondary antibody response upon a single injection of DNP-Salm, while preimmunization with Salmonella bacilli had no influence on anti-DNP response induced by subsequent immunization with DNP-Salm. It was further confirmed that primed T cell have no "suppressor activity" on the anti-DNP antibody response, by a simple cell transfer of DNP-Salm.primed thymocytes or spleen cells into recipients that were concurrently immunized with DNP-Salm. These results indicate that sequential production of hapten-specific IgM and IgG antibody is induced by DNP-Salm.without involvement of Salmonella-specific T cells. On the other hand, it was noted that time-dependent increase in antibody affinity was not observed in animals secondarily immunized with DNP-Salm.at different intervals. The results indicate that IgM B cells would autonomously differentiate into IgG B cells upon stimulation with DNP-Salm., however, further maturation of antibody affinity was not induced by this T cell-independent antigen.

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