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Biomedical subjects

T Shiba

Publications and source records attributed to T Shiba.

At least 271 records · Page 15Linked to original sources
PubMed1980

Liposomes as vehicles for vaccines.

Lipid A from Shigella flexneri LPS, or acylated derivatives of muramyl dipeptide (MDP), were incorporated into the lipid bilayer of liposomes to enhance the adjuvanticity of the liposomes in rabbits. Liposomes containing lipid A induced antibodies against lipid A, phosphocholine, phosphatidylcholine, and sphingomyelin. Lipid A was resolved into eight fractions, some of which did, and others of which did not, induce antibodies against liposomes. Anti-liposome antibodies also were induced (in the absence of liposomes) by complete Freund's adjuvant, and by acid treated bacterial cells coated with lipid A, but were not induced either by lipid A or liposomes alone, or by liposomes containing acylated MDP. We tested the liposomes for the ability to enhance the immunogenicity of a protein antigen. The antigen consisted of liposomes having acylated MDP and ganglioside GM1 (the receptor for cholera toxin, or CT) in the lipid membrane, and CT bound to the outer surface of the liposomes. The liposomal antigen (having surface-bound CT) produced a much greater anti-CT titer than that obtained by injection of CT alone. We conclude that liposomes containing only phosphatidylcholine, cholesterol, and dicetyl phosphate are poorly immunogenic, but that antibodies against them can be induced by inclusion of lipid A. Liposomes that are appropriately formulated can strongly enhance the immunogenicity of a liposome-bound protein antigen.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1980

Mitogenic effects of bacterial cell walls and their components on murine splenocytes.

Stimulation of splenocytes from ICR mice by cell walls of 17 species of gram-positive bacteria, and peptidoglycans and water-soluble enzymatic digests prepared from some of them, and by synthetic N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) was studied in terms of mitogenic activity. All the cell walls tested except those of Micrococcus lysodeikticus, regardless of their mycolic acid content and immunopotentiating activity, had definite stimulatory activity on splenocytes. In general, the cell walls of mycobacteria, nocardia, and stretomyces had stronger mitogenic activity than other cell walls. The mitogenic activity of cell walls was mainly attributable to a peptidoglycan moiety, and the activity was retained even when the peptidoglycan had been degraded into a monomer or a dimer of its subunit, though a polymerized form of the subunits exhibited stronger activity than the monomer or dimer. Definite mitogenicity of synthetic MDP on splenocytes from ICR mice was also confirmed. The origin of the unknown principle(s) that is found in the cell walls of nocardia, mycobacteria and streptomyces and is responsible for their potent mitogenic activity on murine splenocytes was discussed.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Dynamics of kallikreinogen under hemodialysis.

There are many complications due to hemodialysis, causes of which seem to lie under disorders of the coagulation system, fibrinolytic system, and kinin system. Therefore, it is important to understand the dynamics of these systems during hemodialysis. Accordingly, kallikreinogen, plasminogen, plasmin inhibitors, contact factor, antithrombin, and prothrombin were assayed during the experimental dialysis, experimental ultrafiltration and clinical hemodialysis. Plasmin inhibitors decreased remarkably by dialysis. They then recovered the pre-dialytic values as time went on. Kallikreinogen did not show any definite tendency immediately after the beginning of dialysis, but two hours later its value rather increased relative to thepre-dialytic value. It was supposed that this increase was caused by reactive hyperproduction due to gradual consumption of kallikreinogen. Contact factor slightly decreased by dialysis, whereas prothrombin and antithrombin decreased apparently. When hemodialysis is practiced, it is necessary to fully realize that the coagulation system, fibrinolytic system, and kinin system might lose their balance.

Antithrombins↗
PubMed1979

Distribution of aerobic bacteria which contain bacteriochlorophyll a.

Sixteen strains of aerobic bacteria which contain bacteriochlorophyll a were isolated from the samples collected in aerobic marine environments: thalli of Enteromorpha linza, Porphyra sp., Sargussum horneri; beach sand; and the surface seawater from Aburatsubo Inlet. When they occurred, their proportions among the aerobic heterotrophic populations ranged from 0.9 to 1.1% in the seaweed samples and from 1.2 to 6.3% in the beach sand samples and were 0.9% in the seawater sample. The results suggested that the aerobic photopigmented bacteria widely inhabit aerobic marine environments.

Journal Article↗
PubMed1979

Stimulation of the reticuloendothelial system of mice by muramyl dipeptide.

Muramyl dipeptide (MDP), a part of bacterial cell wall peptidoglycans, was active as adjuvant and stimulated the reticuloendothelial system (RES) of mice to increase its phagocytic function. A series of analogs of MDP was tested for their adjuvant activity and RES-stimulating activity. Sex differences were observed in the adjuvant activity and RES-stimulating capacity of some MDP analogs. A stereochemically highly specific structure required for MDP to exert adjuvant activity was also required for its RES-stimulating activity. Based on this close correlation among the structure, adjuvant activity, and RES-stimulating capacity of MDP, we infer that macrophages may play an important role in the expression of adjuvant activity of MDP.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Inhibition of macrophage migration by muramyl peptides.

In the capillary tube migration system a synthetic muramyl dipeptide (MDP; N-acetylmuramyl-L-alanyl-D-isoglutamine), a part of bacterial cell wall peptidoglycans, inhibited the migration of peritoneal exudate macrophages from normal guinea pigs or rats. The migration inhibition was also caused by some MDP-containing peptidoglycan fragments from cell walls of Lactobacillus plantarum and Staphylococcus epidermidis. The migration inhibition could not be explained on the basis of macrophage migration inhibitory factor. A stereochemically highly specific structure of MDP required for its adjuvant activity was also required for the macrophage migration inhibition. These findings suggest that MDP and MDP-containing cell wall fragments may activate macrophages and that this activation may be important in the exertion of their adjuvant activity.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Adjuvant activities in production of reaginic antibody by bacterial cell wall peptidoglycan or synthetic N-acetylmuramyl dipeptides in mice.

This paper is concerned with the adjuvant activity in stimulatory immunoglobulin E production against ovalbumin (OA) by bacterial cell walls, cell wall peptidoglycan (PG), and their PG fragments and synthetic N-acetylmuramyl (MurNAc) dipeptides in A/J mice. A PG isolated from Streptococcus pyogenes, PG subunit polymer and dimer obtained from Staphylococcus epidermidis, and water-soluble fragments of cell walls or PG prepared from Nocardia corynebacteriodes and Streptomyces gardneri were found to enhance both the primary and secondary responses of anti-OA immunoglobulin E antibody production. It was suggested that the PG portion, either intact or highly degraded, was capable of enhancing the immunoglobulin E antibody production, and there was no need for the non-PG moiety or intactness of PG structure for the adjuvant activity. This finding was confirmed and extended by the use of synthetic MurNAc dipeptides. Among eight MurNAc dipeptides tested, MurNAc-l-Ala-d-isoGln, MurNAc-l-Ala-d-Gln, MurNAc-l-Ala-d-Glu, and MurNAc-l-Ser-d-isoGln were found active as an adjuvant in the stimulation of the primary and secondary reaginic anti-OA antibody production in a similar way to the cell wall PG and their fragments. None of the synthetic MurNAc-l-Ala-l-isoGln, MurNAc-l-Ala-l-Gln, MurNAc-l-Ala-l-Glu, and MurNAc-l-Ala-d-isoAsn, on the other hand, stimulated the anti-OA immunoglobulin E antibody production in either primary or secondary response, indicating the importance for the adjuvancy in immunoglobulin E production of the configuration of the glutamic acid residues adjacent to the l-Ala (or l-Ser) in muramyl dipeptides.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Macrophage activation by bacterial cell walls and related synthetic compounds.

Activation of peritoneal macrophages from guinea pigs by various bacterial cell walls, M-1 endo-N-acetylmuramidase enzymatically digested bacterial cell walls and synthetic muramyl dipeptides was studied in terms of stimulation of [14C] glucosamine incorporation. All test bacterial cell wall preparations significantly increased a [14C]glucosamine uptake by the macrophages. Some of the water-soluble M-1 enzyme digests also exerted stimulating effects on macrophages, although the activity of the digests was found to be weaker than those of original cell walls. Furthermore, an adjuvant-active synthetic MurNAc-L-Ala-D-isoGln (MDP) showed a weak but significant activity, whereas an adjuvant-inactive analog, MurNAc-L-Ala-L-iso-Gln, did not show a significant activity, at least with the dose of 100 microgram. Additional studies with 6-O-acyl derivatives of MDP revealed that 6-O-(2-tetradecylhexadecanoyl)-MDP and 6-O-(3-hydroxy-2-tetradecyl-octadecanoyl)-MDP exhibit stronger macrophage-stimulating effects than MDP. It can be concluded from the above findings that MDP is the essential structure responsible for stimulating the activity of cell walls on guinea pig peritoneal macrophages, but it requires a particle state, which results from an additive character of lipophilicity, to exert the activity fully and effectively.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Mitogenic effects of bacterial cell walls, their fragments, and related synthetic compounds on thymocytes and splenocytes of guinea pigs.

Stimulation of [(3)H]thymidine incorporation of thymocytes and splenocytes from guinea pigs by various bacterial cell walls and their peptidoglycans, by enzymatic digests, and by synthetic muramyl dipeptides was studied as an indication of mitogenic activity. Cell wall and peptidoglycan preparations, isolated from 19 strains belonging to 18 different species, definitely increased [(3)H]thymidine incorporation of thymocytes as well as splenocytes, regardless of mycolic acid contents as a non-peptidoglycan component. Both the cell walls from Nocardia corynebacteriodes (containing mycolic acids) and those from Streptomyces gardneri (lacking mycolic acids) showed far stronger mitogenic activities on splenocytes than other cell walls (stimulation index, 25 to 30). Furthermore, water-soluble enzymatic digests, notably the endopeptidase digests, which generally were greater in degree of polymerization of peptidoglycan subunits than the glycosidase digests obtained from representative cell walls, were found to have as distinct a stimulating activity on splenocytes as the original cell walls. In contrast, solubilization of the cell walls by enzymes, irrespective of endopeptidases or glycosidases, was accompanied by disappearance of the mitogenic activity on thymocytes. On the other hand, studies with synthetic 6-O-acyl-MurNAc-l-Ala-d-isoGln preparations (6-O-acyl-MDPs) revealed that 6-O-stearoyl-MDP and 6-O-(2-tetradecylhexadecanoyl)-MDP, unlike MDP, had distinct mitogenic activity on thymocytes, whereas their activity on splenocytes was rather weaker than MDP itself. The findings presented here suggest that MDP is the minimal structure for the mitogenic activities of bacterial cell walls on guinea pig splenocytes, but that MDP, though distinctively active by itself, requires a polymerized form to exert effectively its inherent stimulating activities on splenocytes. On the other hand, on thymocytes, MDP, unless it takes a particular form or has appropriate additive groups, cannot exert its mitogenic activities.

Acetylmuramyl-Alanyl-Isoglutamine↗