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Biomedical subjects

S Kotani

Publications and source records attributed to S Kotani.

At least 163 records · Page 9Linked to original sources
PubMed1983

Immunobiological activities of synthetic lipid A analogs and related compounds as compared with those of bacterial lipopolysaccharide, re-glycolipid, lipid A, and muramyl dipeptide.

Thirteen acylated and phosphorylated derivatives of beta-1,6-linked glucosamine disaccharide (lipid A analogs), which were synthesized after the structural model of Salmonella-type lipid A, and seven similar derivatives of glucosamine monosaccharide (lipid A-related compounds) were studied for their immunobiological activities. These included mitogenicity and polyclonal B cell activation enhancement of migration of monocytes and polymorphonuclear leukocytes derived from human peripheral blood, stimulation of guinea pig peritoneal macrophages, activation of human complement, and stimulation of serum antibody production and induction of delayed-type hypersensitivity against ovalbumin in guinea pigs. Comparisons were made with lipid A, RE-glycolipid, lipopolysaccharide of natural sources, and a well-known synthetic adjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine. Some of the lipid A analogs were found to manifest the mitogenic, polyclonal B cell-activating macrophage-stimulating, complement-activating, and immunostimulating activities, although the observed activities were generally far less than those of natural products in intensity and efficiency. Other immunobiological effects exhibited by most of the synthetic lipid A analogs were the enhancement of migration of monocytes and polymorphonuclear leukocytes. It is premature to draw definite conclusions on structure-activity relationships, since a few compounds which were active in some assay systems were scarcely active in other assays. However, an indisputable fact was that beta-1,6-glucosamine disaccharide 1 alpha,4'-diphosphate, which carries two amide-bound (R)-3-hydroxytetradecanoyl and three ester-bound tetradecanoyl residues, and thus has the structure most closely resembling natural lipid A among test compounds in this study, was definitely active in all of the present assay systems. However, its potency was generally much less than natural products. Some of glucosamine monosaccharide derivatives, especially N-(R)-3-[(R)-3-hydroxytetradecanoyloxy]tetradecanoyl glucosamine, also exerted all of the in vitro activities described above. This fact suggests that a glucosamine disaccharide structure may not necessarily be a prerequisite as far as the in vitro immunobiological activities tested are concerned.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

Contractile effects of bacterial cell walls, their enzymatic digests, and muramyl dipeptides on ileal strips from guinea pigs.

Cell walls isolated from four bacterial species (Streptococcus pyogenes, Lactobacillus plantarum, Streptomyces gardneri, and Nocardia corynebacteriodes), which exhibited the adjuvant effect of stimulating cellular and humoral immune responses against ovalbumin in guinea pigs, caused the slow-starting and long-lasting contraction of guinea pig ileal strips suspended in Tyrode solution. In contrast to these cell walls active in immunoadjuvancy, those isolated from five bacterial species (Micrococcus lysodeikticus, Staphylococcus epidermidis, Arthrobacter atrocyaneus, Corynebacterium insidiosum, and Ampullariella regularis), which lacked immunoadjuvancy at least in intact walls, caused no or very weak contraction of the ileal strips. Further study demonstrated that both a monomer and a polymer of disaccharide-stem peptides, which were obtained by enzymatic degradation of S. epidermis cell wall peptidoglycans, displayed similar contractile effects. It was finally revealed that guinea pig ileum strips showed a definite contractile response to N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and 6-O-stearoyl- and 6-O-(2-tetradecylhexadecanoyl)-MDPs, but not to their analogs, whose C-terminal amino acid was L-isoglutamine or D-isoasparagine in place of D-isoglutamine and which lacked adjuvancy. 6-O-(3-Hydroxy-2-docosylhexacosanoyl)-MDP, on the other hand, caused a slow and lasting relaxation of the ileum strips, but its L-isoglutamine and D-isoasparagine analogs did not.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

Immunological activities of Capnocytophaga cellular components.

Whole cells of a clinical isolate (strain S-3) of the genus Capnocytophaga were divided into cell envelope (CE) and cytoplasm (CP) fractions by mechanical disintegration followed by differential centrifugation, and a part of the CE fraction was further fractionated by sodium dodecyl sulfate (SDS) treatment into the peptidoglycan and SDS-supernatant fractions. The other part of the CE was extracted with butanol-water or hot phenol-water to isolate butanol-lipopolysaccharide and phenol-lipopolysaccharide, respectively. All of the test fractions except CP exhibited multifold immunomodulating activities, namely, the adjuvant activities to cellular as well as humoral immune responses against ovalbumin in guinea pigs, the mitogenicity on splenocytes of guinea pigs and BALB/c mice (but not on their thymocytes), the stimulation of guinea pig peritoneal macrophages (in terms of increased glucosamine uptake), and the activation of the human complement system through alternative as well as classical pathways. In addition, the test fractions other than the CP evoked dermatoxic reactions on rabbit skin with characteristic variations among them. The immunomodulating activities of SDS-supernatant were noteworthy in view of the fact that this fraction was essentially free of muramic acid and diaminopimelic acid and did not cause the gelation of horseshoe crab amoebocyte lysate except when it was used at the very high dose, suggesting that there was practically no contamination by peptidoglycans and lipopolysaccharides in the SDS-supernatant.

Adolescent↗
PubMed1982

Liberation of serotonin from rabbit blood platelets by bacterial cell walls and related compounds.

A study was made on the activity of various bacterial cell walls and peptidoglycans to liberate serotonin from rabbit blood platelets. All of the test cell walls or peptidoglycans prepared from 27 strains of 21 bacterial species were shown to cause a marked release of serotonin, regardless of differences in types of peptidoglycan and non-peptidoglycan moieties and in some biological properties. The assay made with the water-soluble "digests" of Staphylococcus epidermidis cell wall peptidoglycans, which were prepared by use of appropriate enzymes, revealed that a polymer of peptidoglycan subunits (a disaccharide-stempeptide) was definitely active in the release of serotonin, but a structural unit monomer was inactive. Among a variety of synthetic muramylpeptides and their 6-O-acyl derivatives, only 6-O-(3-hydroxy-2-docosylhexacosanoyl)-N-acetylmuramyl-L-alanyl-D-isoglutaminyl- L-lysyl-D-alanine was found to hold a strong serotonin-liberating activity.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

Stimulation of migration of human monocytes by bacterial cell walls and muramyl peptides.

Bacterial cell walls, water-soluble fragments of the wall peptidoglycan, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), and 6-O-acyl derivatives of MDP were examined for migration-stimulating activity on human peripheral blood monocytes by using a multiwell chemotaxis assembly. Cell walls isolated from 11 bacterial species caused a definite increase in monocyte migration, but the walls of Micrococcus lysodeikticus were scarely active. The migration-enhancing activity of Staphylococcus epidermidis cell walls was retained by a monomer as well as a polymer of disaccharide peptides which were prepared by digestion of the peptidoglycan with enzymes. It was finally revealed that the migration of monocytes was enhanced by MDP. 6-O-Octadecanoyl-MDP, 6-O-(2-tetradecylhexadecanoyl)-MDP, and 6-O-(3-hydroxy-2-docosylhexacosanoyl)-N-acetylmuramyl-L-seryl-D-isoglutamine were active, but to a lesser extent. A checkerboard assay demonstrated that the increased monocyte migration caused by S. epidermidis cell walls was directed toward a positive stimulus (chemotaxis).

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

New model of a synthetic adjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine- induced arthritis: clinical and histologic studies in athymic nude and euthymic rats.

A synthetic adjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), induced severe polyarthritis in euthymic rnu/+ rats. The rnu/+ rats were the most susceptible to MDP-induced arthritis among various rat strains tested, whereas congenitally athymic nude rats (rnu/rnu), males or females, did not develop the disease. This disease was clinically and histologically indistinguishable from classic adjuvant-induced arthritis in terms of clinical course, clinical signs, and histologic features such as (1) an initial acute exudative reaction observed primarily in stroma of the synovial membrane, periarticular tissue, about the tendons, tendon sheath, along the periosteum, between muscle bundles and in the subcutaneous tissue; (2) hypertrophy of the synovial villi, hyperplasia of the synovial lining cells; (3) the very active periosteal new bone formation; and (4) granulation tissue growth either in the articular tissues or in liver, lymph nodes, and capsule of the spleen. Thus, it is postulated that MDP-induced arthritis is basically the same disease as classic adjuvant-induced arthritis. The thymus may play an important role in promoting the development of the disease, possibly through some immune mechanisms to undetermined antigen(s). We believe that nonimmune mechanisms may also be involved in some part of acute and chronic inflammatory reactions to MDP molecules. This new model of MDP-induced arthritis will be a very useful tool to elucidate the underlying mechanisms of adjuvant-induced arthritis.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

Isolation of recombinants doubly and triply drug-resistant to streptomycin, tetracycline and chloramphenicol by PEG-induced cell fusion of singly resistant staphylococcus aureus L-forms.

Various combinations of four substrains of Staphylococcus aureus L-form (strain STA-EMT-1), each of which was resistant to one of the following four drugs, streptomycin (SM), tetracycline (TC), chloramphenicol (CP) and erythromycin (EM), were submitted to polyethylene glycol (PEG)-induced cell fusion. PEG-induced cell fusion followed by enrichment culture in the liquid basal medium supplemented with penicillin G resulted in development of recombinants that were doubly drug-resistant to SM and TC, SM and CP, and TC and CP, but no recombinant doubly resistant to EM and TC, was obtained by treatment of a EM-resistant and TC-resistant substrains with PEG. No recombinants resistant to SM, CP and TC could be obtained by treatment of substrains resistant to SM, CP and TC, respectively, with PEG. But recombinants triply resistant to these three drugs were produced by two-step cell fusion; that is by fusion of a recombinant doubly resistant to two of the three drugs with a substrain resistant to the third drug.

Chloramphenicol↗
PubMed1981

Mitogenic effect of cytoplasmic membranes and a cytoplasmic fraction of Staphylococcus aureus L-forms on human peripheral blood lymphocytes.

The cytoplasmic membranes and a cytoplasmic fraction of Staphylococcus aureus L-forms increased the incorporation of [3H]thymidine by human lymphocytes in the presence of fetal bovine serum. Both fractions stimulated cord blood lymphocytes as well as adult peripheral lymphocytes, suggesting the possibility that the observed effect was not due to an antigen-specific reaction, but to an immunologically nonspecific action. The membrane mitogen(s) was resistant to trypsin, although it was partially solubilized by trypsin treatment. The mitogen(s) could not be extracted with a chloroform-methanol mixture (2:1, v/v), although the chloroform-methanol soluble fraction was strongly mitogenic to murine splenocytes. Human serum which was added to the assay system in place of fetal bovine serum definitely suppressed the mitogenic effect of both cytoplasmic membranes and the cytoplasmic fraction, especially the latter.

Cytoplasm↗
PubMed1981

beta-Lactam resistance in Serratia marcescens: comparison of action of benzylpenicillin, Apalcillin, Cefazolin, and ceftizoxime.

The intrinsic mechanisms of resistance to beta-lactam antibiotics in Serratia marcescens IFO 12648 were investigated, comparing the action of benzylpenicillin, apalcillin, cefazolin, and ceftizoxime. The minimal inhibitory concentrations for this strain were 1,600, 3.13, 6,400, and 0.05 microgram/ml, respectively. The addition of ethylenediaminetetraacetic acid markedly reduced the minimal inhibitory concentrations of benzylpenicillin and cefazolin, whereas those of apalcillin and ceftizoxime were not influenced. S. marcescens IFO 12648 produced only a low level of beta-lactamase activity constitutively, and the production was considerably increased by the addition of benzylpenicillin. Cefazolin was hydrolyzed rapidly by beta-lactamase activity, whereas benzylpenicillin, apalcillin, and ceftizoxime were poorly hydrolyzed. Peptidoglycan synthesis in ether-treated strain IFO 12646 cells was inhibited by a concentration of ceftizoxime markedly lower than that of cefazolin and by a concentration of apalcillin moderately lower than that of benzylpenicillin.

Ampicillin↗
PubMed1981

Role of thymus for N-acetyl muramyl-L-alanyl-D-isoglutamine-induced polyarthritis and granuloma formation in euthymic and athymic nude rats or in neonatally thymectomized rats.

A synthetic adjuvant, N-acetyl muramyl-L-alanyl-D-isoglutamine (MDP), produced extremely severe polyarthritis with almost 100% incidence in Rowett euthymic rnu/+ rats, but the same dose of MDP (100 microgram) did not produce the disease in athymic rnu/rnu rats. Five hundred micrograms of MDP or 0.2 mg of heat-killed Mycobacterium bovis BCG, however, produced mild and transient polyarthritis in nude rats with very low incidence. We have not yet succeeded in reconstituting the disease susceptibility of nude rats by using thymus cells from normal rnu/+ rats. After intradermal inoculation of 100 microgram of MDP, nude rats developed small granulomas with a little necrosis and very few multinucleated giant cells only in the regional lymph nodes, whereas, in addition to the development of polyarthritis, euthymic rnu/+ rats developed typical granuloma with massive necrosis accompanied by numerous polymorphonuclear leukocytes and sparse multinucleated giant cells in the regional lymph nodes. Thymus cell-reconstituted rnu/rnu rats developed granuloma with sparse giant cells, relatively large areas of necrosis, and many polymorphonuclear leukocytes. Neonatal thymectomy may depress adjuvant-induced arthritis in the high-responder Lewis rats and enhance the disease development in the low-responder F344 rats. These findings suggested that (i) thymus plays an important role in promoting the development of MDP-induced arthritis; (ii) MDP-induced granuloma formation does not require thymus functions; (iii) the thymus functions may however be involved in the development of massive necrosis surrounded by considerable polymorphonuclear leukocyte infiltration, the mechanisms of which remain to be determined; and (iv) there is no direct correlation between granuloma formation and development of adjuvant arthritis.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1981

Chemical and biological properties of a peptidoglycan isolated from Treponema pallidum kazan.

A peptidoglycan layer of Treponema pallidum kazan was isolated by solubilization of whole cells with 1% warm sodium dodecyl sulfate and subsequent digestion of an insoluble residue with proteases. Electron microscopy revealed that the peptidoglycan was isolated as a single-layered sacculus of less than 5 nm in thickness, freed from axial filaments and an envelope sheath. An isolated peptidoglycan fraction was mainly composed of glucosamine, muramic acid, alanine, glutamic acid, ornithine, and glycine in molar ratios of 0.65:0.68:1.63:1.00:0.75:1.03. Amino (N)- and carboxyl (C)-terminal amino acid analyses suggested the involvement of at least a part of the glycine residue in cross-linking between the amino group of ornithine residue at one strand of the stem peptide subunit and the carboxyl group of alanine of the neighboring strand. The treponemal peptidoglycan lacked the immunoadjuvant activity both to stimulate antibody production and to induce delayed-type hypersensitivity against ovalbumin, as well as the properties necessary to stimulate guinea pig and mouse splenocytes and guinea pigs peritoneal macrophages, unlike the cell walls or peptidoglycans (group A type of Schleifer and Kandler's classification, Bacteriol. Rev. 36:407-477, 1972) isolated from many bacterial species parasitic to the mammal. However, the peptidoglycan activated the human complement system through the alternative pathway, as well as the classical one, and caused a liberation of 5-hydroxytryptamine in rabbit blood platelets in a similar manner to the cell wall peptidoglycans of both group A and B types.

Amino Acids↗
PubMed1981

Adherence of Streptococcus sanguis clinical isolates to smooth surfaces and interactions of the isolates with Streptococcus mutans glucosyltransferase.

Streptococcus sanguis isolated from human dental plaque were grown in Todd-Hewitt broth. Cells were collected by centrifugation and lyophilized after extensive washing with water. The cell-associated glucosyltransferase (GTase) activities of S. sanguis strains were assayed with [14C]sucrose. Strain differences in GTase activity were significant within the same serotype or biotype or both. The ability of S. sanguis cells to adhere to smooth glass surfaces was generally weak, irrespective of significant cell-associated GTase activity synthesizing water-insoluble, gel-like glucans. Resting cells of most S. sanguis strains bound extracellular GTase from Streptococcus mutans strain B13 (serotype d), resulting in the strong adherence of the S. sanguis cells to smooth glass surfaces in the presence of sucrose. Conversely, S. mutans B13 cells also could bind extracellular GTase from some strains of S. sanguis examined. The sucrose-dependent adherence of S. mutans cells was not altered, although S. sanguis strains from which the extracellular GTases were obtained did not produce significant adherence in the presence of sucrose. In view of these findings, it was suggested that S. mutans GTase could affect the adherence of S. sanguis to smooth tooth surfaces in the oral cavity.

Binding Sites↗