Search PubMed⌕ Search

Biomedical subjects

S Nonoyama

Publications and source records attributed to S Nonoyama.

At least 73 records · Page 4Linked to original sources
PubMed1990

Phenotypic profile and functions of T cell receptor-gamma delta-bearing cells from patients with primary immunodeficiency syndrome.

TCR-gamma delta-bearing T cells have been reported to be increased in several immunodeficient patients. However, their functional role and phenotypic characterization have not yet been well documented. In this study we examined the surface phenotypes and functional properties of TCR-gamma delta+ cells from several patients with primary immunodeficiency syndrome. It was demonstrated that TCR-gamma delta+ cells detected by TCR-delta 1 mAb were increased in some of the patients, particularly in patients with Wiskott-Aldrich syndrome and severe combined immune deficiency. The TCR-gamma delta+ cells showed such a unique profile that more than 60% of the cells expressed delta-TCS1, which is normally present in a lesser amount, and that most of the cells lacked CD5 T lineage marker. TCR-gamma delta+ cells from the patients with primary immunodeficiency syndrome served as NK cells as observed in normal individuals, while displaying weak LAK and allogeneic cell-specific killer activities. The TCR-gamma delta+ cells were classified into several subpopulations according to their antigenic phenotype, then their NK activity of normal individuals and patients, lymphokine-activated killer and allo-specific killer activities of normal individuals were compared among the subpopulations. Delta-TCS1+ cells mediated almost the same killer activities as total TCR-gamma delta+ cells, whereas CD8+ TCR-gamma delta+ cells displayed stronger cytotoxic activities in both normal subjects and the patients with primary immunodeficiency syndrome.

Antibodies, Monoclonal↗
PubMed1989

Only dull CD3+ thymocytes bind to thymic epithelial cells. The binding is elicited by both CD2/LFA-3 and LFA-1/ICAM-1 interactions.

In view of the necessity for thymocytes to interact with thymic epithelial cells to differentiate into mature T cells, this study analyzed the binding between human thymocytes, cultured thymic epithelial cells (CTEC) and the required adhesion molecules. Immediately after separation, thymic epithelial cells (TEC) readily expressed ICAM-1, which is one of the ligands of LFA-1 cell adhesion molecules. However, the ICAM-1 expression was gradually lost upon culture of TEC. IFN-gamma re-induced ICAM-1 on the CTEC, and the ability of CTEC to bind to thymocytes was also increased by IFN-gamma treatment. The increase in binding seemed to be caused by the LFA-1/ICAM-1 interaction, since it was inhibited by anti-ICAM-1 monoclonal antibody (mAb) and anti-LFA-1 mAb. This suggests that the LFA-1/ICAM-1 interaction is also involved in vivo with the binding of thymocytes to TEC, which have been shown to express ICAM-1. To better understand the nature of the cells involved in binding, thymocytes were sorted into CD3-, CD3dull+, and CD3bright+ subsets (which are supposed to represent the immature, intermediate and mature stages of differentiation, respectively), and were examined for their binding to IFN-gamma-treated CTEC. The result showed that only the CD3dull+ subset bound to CTEC. CD3-, CD3bright+ cells and peripheral blood T lymphocytes did not bind, but they were induced to bind by neuramidase treatment All these bindings were inhibited by anti-LFA-1 mAb and anti-CD2 mAb. These findings indicate that CD3dull+ cells can bind to TEC via CD2/LFA-3 and LFA-1/ICAM-1 interactions. Other cells seemed not to bind to TEC because of sialylation.

Antibodies, Monoclonal↗
PubMed1989

Gas chromatographic assay and disposition of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, in healthy volunteers.

Quantitative determinations of plasma concentrations of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, and its urinary metabolite, 6-chloro-2-pyridinecarboxylic acid (metabolite 1), were obtained using GC with a 63Ni electron-capture detector. 6-Chloro-2-pyridylmethyl nitrate was extracted from plasma with n-pentane. Metabolite 1 was extracted from acidic urine with ethylacetate, back extracted with 0.1 M NaHCO3, and methylated with boron trifluoride methanol reagent. The internal standard for metabolite 1 determination was prepared by propylation of metabolite 1 with boron trifluoride n-propanol reagent. The formation of the esters was confirmed by the GC-MS results. These methods proved to be sensitive and reproducible. A single dose of 6-chloro-2-pyridylmethyl nitrate (5, 10, 20, 40, or 60 mg) was given perorally to healthy volunteers. From the data, a large interindividual variability in the apparent plasma clearance was apparent (85.5 +/- 123 L/min; CV 144%). However, metabolite 1 was the main metabolite in human urine, and the interindividual variation was slight (CV 13%).

Administration, Oral↗
PubMed1989

Lymphocytes after autologous and allogenic bone marrow transplantation.

Lymphocyte reconstitution after bone marrow transplantation (BMT) was analyzed using two-color flow-cytometry in 18 patients and the differences between allogenic and autologous BMT were studied. The CD8 (+) CD11b (+) and CD8 (+) Leu7 (+) suppressor subsets were increased while the CD4 (+) 2H4 (+) suppressor inducer subset was decreased in both groups after BMT. These variations of suppressor associated subsets persisted for more than 100 days and were considered to be related to immunologic abnormalities in post-BMT patients. In addition, Ia (+) T cells were increased in both autologous and allogenic BMT patients. This increase appears not to be caused by reaction to allo-antigens, but rather reflects the reconstitution of the lymphocyte system after BMT. In contrast, the CD16 (+) NK cell subset was increased specifically in allogenic BMT patients and only for a short time following transplantation.

Adolescent↗
PubMed1989

Suppression of in vitro immunoglobulin synthesis by CD16(Leu11a)+ CD56 (NKH1,Leu19)+non-T lineage NK cells; lack of suppression of cells from immunodeficient patients.

We examined the effect of both CD3-CD16(Leul la)+CD56(NKH1,Leu19)+ non-T lineage natural killer (NK) cells and CD3+CD8+CD16-CD56+ T lineage NK cells on B cell proliferation and differentiation. Fluorescence-activated cell sorter (FACS) purified CD16+CD56+ cells suppressed pokeweed mitogen (PWM) induced immunoglobulin synthesis. However, the T lineage NK cells tended to suppress immunoglobulin synthesis only when CD8+ cells were eliminated from the culture, and even then CD16+ NK cells suppressed antibody production more efficiently than did CD3+CD8+ NK cells. CD16+ NK cells did not suppress B cell proliferative responses to several mitogens. CD16+ NK cells from patients with Wiskott-Aldrich syndrome, who showed the high percentage of CD16+ NK cells, did not inhibit immunoglobulin synthesis. We concluded that non-T NK cells are the major immunoregulatory NK cells for immunoglobulin synthesis in normal immune systems, and that they suppress immunoglobulin synthesis through their action on B cell differentiation.

Adult↗
PubMed1987

Cytoplasmic CD3 antigen and T cell receptor gene rearrangement in surface CD3 negative T cell malignancy.

In the present study, it was our intention to further the characterization of the neoplastic cells at the early stage of the T lineage, which were defined as those which bore pan-T marker(s) (CD2, CD5 and CD7) but not CD3 antigen on the surface. We studied six such cases of leukemia and two such cases of lymphoma for their phenotypes including cytoplasmic CD3 detected with flow cytometry and for the rearrangement of T cell receptor and immunoglobulin genes. The cytoplasmic expression of CD3 antigen in adult thymic cells was also studied. CD7 was expressed in seven cases, the exception being one presumably of B lineage, and rearrangements of T cell receptor gene were detected in five cases. Four cases out of these five genotypic T neoplasms had surface phenotypes compatible with the stage of thymic cells and, interestingly, they all displayed CD3 in the cytoplasm. With regard to normal cells, cytoplasmic CD3 was shown to be present only in a small population of surface CD3 negative thymic cells. These malignant cells, therefore, may have originated from such cells. The exact origins of the two cases bearing pan-T marker(s) with no rearrangement of the T cell receptor gene has not yet been determined.

Adolescent↗
PubMed1986

Protective effect of Nocardia rubra cell wall skeleton on experimental infection in normal and immunosuppressed mice.

The protective effect of Nocardia rubra cell wall skeleton (N-CWS) on experimental infections was investigated in normal and immunosuppressed mice. Pretreatment with N-CWS provided protection against acute systemic infections due to Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens and Listeria monocytogenes in normal mice. N-CWS administered before or after challenge also showed protective activity against Herpes simplex virus infection in normal mice. N-CWS was the most effective against extracellular parasitic Pseudomonas aeruginosa infection when administered 1 day before challenge, but displayed the most potent protective activity against infection with Listeria monocytogenes, a facultative intracellular parasite, when administered 7 to 14 days before challenge. In mice with subcutaneous Pseudomonas aeruginosa infection, N-CWS suppressed abscess formation and decreased the viable cell count in the resultant abscess foci when administered either intraperitoneally or subcutaneously to the infected site. In addition, treatment with N-CWS markedly restored host defense ability against pseudomonal infection in mice immunosuppressed with cyclophosphamide, hydrocortisone and X-ray irradiation.

Animals↗
PubMed1986

In vivo activation of functional properties in mouse peritoneal macrophages by Nocardia rubra cell wall skeleton.

Exudative cells in the peritoneal cavity of mice, particularly polymorphonuclear leukocytes significantly increased 1 day after intraperitoneal injection of Nocardia rubra cell wall skeleton (N-CWS). Macrophages and lymphocytes significantly increased 4 to 7 days after injection. N-CWS also enhanced peritoneal macrophage functions such as phagocytosis of latex particles, production of superoxide anion, production and secretion of lysosomal enzymes such as beta-glucuronidase, lysozyme and acid phosphatase, phagocytosis and intracellular killing of bacteria, and in vitro chemotaxis. The phagocytic function of the reticuloendothelial system was also enhanced. These results indicate that macrophages were activated in vivo by N-CWS.

Animals↗
PubMed1980

Inhibitory effect of Pseudomonas aeruginosa on phagocytosis and killing of rabbit polymorphonuclear leukocytes.

Polymorphonuclear leukocyte (PMN)-resistant strains of Pseudomonas aeruginosa had the ability to interfere with phagocytosis of Escherichia coli, whereas PMN-sensitive strains of P. aeruginosa did not. When mice were infected with an ordinarily nonpathogenic strain of E. coli, addition of a PMN-resistant strain of P. aeruginosa gave a mortality considerably higher than that obtained with P. aeruginosa alone, whereas addition of a PMN-sensitive strain of P. aeruginosa gave a mortality not different from that observed with P. aeruginosa alone. This increased mortality in mixed infection with E. coli and PMN-resistant P. aeruginosa was obtained by facilitation of tissue invasion by both bacteria from the inoculum site.

Animals↗
PubMed1980

In vitro and in vivo antibacterial activities of FR-31564, a new phosphonic acid antibiotic.

FR-31564, a new phosphonic acid antibiotic, was active against most Gram-negative bacteria except Serratia marcescens and glucose-nonfermenting Gram-negative rods excluding Pseudomonas aeruginosa. The antibacterial activity in vitro of FR-31564 was stronger than that of fosfomycin especially against Escherichia coli, Klebsiella pneumoniae, Enterobacter species and P. aeruginosa. FR-31564 also was active against Gram-negative bacteria resistant to beta-lactam antibiotics and against gentamicin-resistant strains of P. aeruginosa. The antibacterial activity in vitro of FR-31564, like that of fosfomycin, was enhanced when 10% rabbit blood was added to the nutrient agar. The therapeutic efficacy of FR-31564 in experimental infections in mice was superior to that of fosfomycin in infections due to most Gram-negative bacteria used, and was similar to that of gentamicin in infections due to Citrobacter freundii, Proteus rettgeri and Proteus inconstans B. The protective effect of FR-31564, particularly in the P. aeruginosa infection, was superior to that of other control drugs including gentamicin.

Animals↗
PubMed1979

Inhibitory effect of Pseudomonas aeruginosa on the phagacytic and killing activities of rabbit polymorphonuclear leukocytes: purification and characterization of an inhibitor of polymorphonuclear leukocyte function.

A clinically isolated strain of polymorphonuclear leukocyte (PMN)-resistant Pseudomonas was found to produce an extracellular substance (PMN inhibitor) that inhibits the phagocytic and killing activities of PMN. The PMN inhibitor was purified from culture filtrates by precipitation with (NH4)2SO4 and chromatography on phosphocellulose, diethylaminoethyl-cellulose, and Sephadex G-100. The preparation was homogenous as judged by disc gel electrophoresis. The purified PMN inhibitor appeared to be a protein with a molecular weight of approximately 65,000 that was inactivated by heating and by exposure to a proteolytic enzyme.

Animals↗
PubMed1979

Inhibitory effect of Pseudomonas aeruginosa on the phagocytic and killing activity of rabbit polymorphonuclear leukocytes: mechanisms of action of a polymorphonuclear leukocyte inhibitor.

The polymorphonuclear leukocyte (PMN) inhibitor isolated from a strain of Pseudomonas aeruginosa which is resistant to the phagocytic and killing activities of rabbit PMN inhibited migration of PMN and engulfment of latex particles by PMN. In studies of the bactericidal metabolism of PMN, the PMN inhibitor did not inhibit the intracellular activity and extracellular release of lysosomal enzymes. However, the PMN inhibitor caused a decrease of Nitro Blue Tetrazolium reduction. The PMN inhibitor had a cytotoxic effect on PMN and inhibited [14C]tyrosine uptake in intact PMN inhibitor had no inhibitory effect on protein synthesis in cell extracts.

Animals↗
PubMed1977

Nocardicin A, a new monocyclic beta-lactam antibiotic III. In vitro evaluation.

Nocardicin A, a new monocyclic beta-lactam antibiotic, exerts a comparatively potent antimicrobial activity against gram-negative organisms, especially Pseudomonas aeruginosa, the indole-positive and indole-negative Proteus groups (except Pr. morganii), Serratia marcescens and the Neisseria groups. The in vitro antimicrobial activity of nocardicin A against clinical isolates of Ps. aeruginosa was about twice that of carbenicillin. The mean MICs of nocardicin A for Pr. mirabilis, Pr. rettgeri and Pr. inconstans ranged from 3.13 to 12.5 microgram/ml and were 25 similar to 50 microgram/ml for Pr. vulgaris. Nocardicin A in concentrations of 12.5 similar to 50 microgram/ml inhibited 30 strains (48 percent) of S. marcescens usually resistant to beta-lactam antibiotics. However, nocardicin A had no significant in vitro activity against Staphylococci and Escherichia coli. No cross-resistance was seen between nocardicin A and other beta-lactam antibiotics. This antibiotic was stable to beta-lactamase. The in vitro activity of nocardicin A against Ps. aeruginosa and Pr. mirabilis was greatly influenced by the assay media used. Nocardicin A was bactericidal and appeared to act synergistically with serum bactericidal factors against Ps. aeruginosa and with polymorphonuclear leukocytes against Ps. aeruginosa, E. coli and Pr. vulgaris. The bactericidal activity of nocardicin A against the above 3 organisms, therefore, increased markedly in the presence of fresh serum and polymorphonuclear leukocytes.

Animals↗