[Clinical evaluation of serum CEA level in various malignant tumors (author's transl)].
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Biomedical subjects
Publications and source records attributed to F Kinoshita.
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Substitution of the L-alanine residue by L-serine and glycine in an N-acetylmuramyl-L-alanyl-D-isoglutamine, the minimum structural unit essential to the immunoadjuvancies characteristic of bacterial cell wall peptidoglycans, was shown to bring about significant increase and some decrease, respectively, in the adjuvant abilities of molecules to induce delayed-type hypersensitivity and to stimulate serum antibody levels to ovalbumin when administered to guinea pigs as a water-in-mineral oil emulsion. N-Acetylmuramyl-D-alanyl-D-isoglutamine, on the other hand, was found to be adjuvant-inactive.
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Addition of a lauroyl, stearoyl or docosanoyl group to the primary hydroxy group at the C-6 position of N-acetylmuramyl-L-alanyl-D-isoglutamine gave lipophilic derivatives that had definite adjuvancies in induction of delayed-type hypersensitivity and enhancement of antibody production against a test protein antigen, ovalbumin, when administered to guinea pigs as liposomes, that is without mineral oil. When administered as mineral oil-in-water emulsion, including Ribitype emulsions, rather than as water-in-mineral oil emulsions, N-acetylmuramyl-L-alanyl-D-isoglutamine and its 6-O-acyl derivatives showed only weak immunoadjuvancies.
The cell walls from several bacterial species whose peptidoglycans are the group B types (Schleifer and Kandler) and those of two arthrobacters were shown to be inactive or only weakly active as an immunoadjuvant in both induction of delayed-type hypersensitivity and stimulation of circulating antibody levels to ovalbumin when administered to guinea pigs as a water-in-oil emulsion, in sharp contrast to the adjuvant-active cell walls of the group A peptidoglycan types which were previously studied. The possible reason for the inabilities as an adjuvant of these cell walls was discussed in relation to the chemical structures of peptidoglycans.
Water-soluble adjuvant-active fractions prepared by digestion of the cell walls from several gram-positive bacteria with an endo-N-acetylmuramidase (Mutanolysin) were shown to gelate the amoebocyte lysate of Tachypleus tridentatus, the Japanese horseshoe crab. This finding was further extended by examination of the clotting activities on the amoebocyte lysate of a synthetic N-acetylmuramyl-L-alanyl-D-isoglutamine and related compounds, either adjuvant-active or -inactive, demonstrating that there are in general close correlations between the abilities to initiate lysate gelation, immunoadjuvancies and pyrogenicities, although there are some exceptions.
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