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Biomedical subjects

M Tsujimoto

Publications and source records attributed to M Tsujimoto.

At least 253 records · Page 14Linked to original sources
PubMed1987

Tumor necrosis factor: receptor binding and mitogenic action in fibroblasts.

Until about two years ago, the only known function of tumor necrosis factor (TNF) was inhibition of tumor growth. Since then it has become apparent that many types of normal and transformed cells express specific high-affinity TNF receptors (Kd 200 pM) and that the presence of receptors does not correlate with susceptibility to the cytotoxic/cytostatic action of TNF. Recent evidence shows that TNF exerts a variety of other important biological activities on cells in culture and in the intact organism. Among the newly recognized activities is a potent mitogenic effect in fibroblasts. Many of the activities of TNF overlap the actions of interleukin-1 (IL-1).

Animals↗
PubMed1987

Comparative studies of the biological activities of human tumor necrosis factor and its derivatives.

Biological activities of human tumor necrosis factor (TNF) and its derivatives were compared. In cytotoxicity assay with L929 cells, one derivative, designated as TNF(Asn), showed significantly lower activity than any other TNF examined. In binding assay, this derivative was also shown to have lower affinity for TNF receptors on L929 cells, suggesting that the cytotoxic activity of TNFs on L929 cells correlates with their affinity for receptors. We also found that the cytotoxic activity of TNF on A673 cells and its inhibitory effect on lipoprotein lipase were parallel with the cytotoxic activity on L929 cells, but the growth-enhancing activity on FS-4 cells and the cytotoxic activity on endothelial cells were not. It was also shown that TNF(Asn) had lower affinity than any other TNF for receptors on these target cells tested. These results suggested that there might be at least two types of cellular responses to TNF; one might correlate with the receptor-binding affinity of TNFs and the other not.

Animals↗
PubMed1987

Tumor necrosis factor-induced permeability increase of negatively charged phospholipid vesicles.

The effect of human tumor necrosis factor (TNF) on the permeability properties of liposomes containing phosphatidylserine at pH 5-6, as demonstrated by the calcein efflux. However, it did not induce any permeability change in such liposomes at neutral pH. The TNF-induced calcein efflux was also observed when an other acidic lipid was used as a component of the liposomes, i.e., phosphatidic acid or dicetyl phosphate. On the other hand, liposomes composed of neutral phospholipids such as phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin showed little increases in permeability when incubated with TNF above pH 5.0. The TNF-induced permeability change was inhibited by the addition of polyaspartic acid, while it was not affected by the presence of 0.5 mM calcium ions. These data suggest that the negative charges on the liposomal surface trigger the interaction between TNF and liposomes. However, when the pH of the reaction mixture was decreased to 4.5, TNF-induced calcein efflux was observed even from neutral liposomes. When TNF was incubated with 8-anilinonaphthalene-1-sulfonic acid, the fluorescence intensity of this fluorophore increased with a decrease in the pH of the solution from 7 to 5, and a drastic increase in fluorescence was observed at pH 4.5. These data suggest that the hydrophobic region of TNF is also important for liposomal damage. Furthermore, the potencies of TNF and its derivative as to the induction of the permeability change paralleled their cytotoxic effects on mouse L929 cells, suggesting that the effect of TNF on liposomal membranes is related to its biological action.

Anilino Naphthalenesulfonates↗
PubMed1987

Tumor necrosis factor-induced downregulation of its receptors in HeLa cells.

Tumor necrosis factor (TNF) induced loss of TNF receptors in HeLa cells was studied using acid elution technique, which could distinguish surface occupancy and real loss of receptors. Exposure of HeLa cells to TNF resulted in a rapid reduction in the number of TNF receptors without affecting the apparent binding affinity. The binding of transferrin after treatment with unlabeled TNF was unaffected. The TNF-mediated decrease in receptor number on the cells was reversible. Following removal of TNF from growth medium, binding activity was restored within 3 h. Cycloheximide prevented the restoration of TNF receptors, suggesting that de novo synthesis of receptors was required to restore the binding activity.

Cycloheximide↗
PubMed1987

Lectin histochemistry of malignant fibrohistiocytic tumors.

The staining pattern by Ricinus communis agglutinin (RCA), a lectin used as a good marker for histiocytes, in 24 cases with malignant fibrous histiocytoma (MFH) was studied and compared with that of 12 cases of fibrosarcoma (FS). In 20 (83%) of 24 cases of MFH, varying degrees of RCA binding were observed, whereas only four (33%) of 12 cases of FS were positive. RCA-positive FS included three cases with infantile FS and one adult case with post-radiation FS. Eight adult patients with FS were entirely negative. This positivity rate of RCA binding in MFH was much higher than those of antisera against lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin previously reported. Seven MFH patients with focal aggregation of RCA-positive benign-appearing (reactive) histiocytes died earlier than the other patients with only scattered RCA-positive histiocytes; 5-year survival rates were 32% and 69%, respectively (p less than 0.05). These findings suggest that RCA reactivity can be used as a potential diagnostic and prognostic marker for MFH.

Adult↗
PubMed1987

Chemical composition and immunobiological activities of sodium dodecyl sulphate extracts from the cell envelopes of Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Fusobacterium nucleatum.

The chemical composition and immunobiological activities in vivo and in vitro of sodium dodecyl sulphate extracts (SDS-SE) derived from periodontopathic bacteria (three strains of Actinobacillus actinomycetemcomitans, two strains of Bacteroides gingivalis, and one strain of Fusobacterium nucleatum) were investigated. The main components of SDS-SE were protein and lipid, with negligible amounts of peptidoglycan and lipopolysaccharide. Immunopotentiating activity was detected in both delayed-type hypersensitivity and antibody formation against the elicitation of a protein antigen with the SDS-SE preparations of A. actinomycetemcomitans ATCC 29524 and B. gingivalis 381 and 1021. On the other hand the SDS-SE of A. actinomycetemcomitans ATCC 29522 enhanced only the induction of a delayed-type hypersensitivity response. All the SDS-SE preparations had mitogenic activity to splenocytes from BALB/c nu/nu, C3H/HeN and C3H/HeJ mice. Migration-stimulating activity for human peripheral blood monocytes was detected especially in the SDS-SE preparations of A. actinomycetemcomitans ATCC 29524 and Y4. All of the SDS-SE samples inhibited [3H]thymidine uptake in human gingival fibroblasts and caused degradation of the cells. The results suggest that the cell membrane components extractable with sodium dodecyl sulphate from periodontopathic bacteria are involved in the pathogenesis of periodontal disease.

Actinobacillus↗
PubMed1987

Possible existence of a novel amphipathic immunostimulator in the phenol-water extracts of Mycobacteriaceae.

The extracts having diverse immunostimulating activities were obtained as a water-phase fraction from four bacterial species representing the 4 genera (Mycobacterium, Nocardia, Gordona, and Rhodococcus) of Mycobacteriaceae by the phenol-water method, which is commonly used for extraction of endotoxic lipopolysaccharides (LPS) from gram-negative bacteria and amphipathic substances from gram-positives. These fractions, especially those of G. aurantiaca and R. terrae, showed strong stimulatory effects on murine splenocytes, macrophages of mice and guinea pigs, the immunoadjuvant activities in guinea pigs and mice, and the distinct activities inducing a tumor necrosis factor and interferons alpha/beta and gamma in primed mice. The fractions from G. aurantiaca and R. terrae exhibited potent pyrogenicity and the ability to activate the clotting enzyme cascade of the horseshoe crab (Tachypleus tridentatus). Some of these biological activities were not very different from the potency of the reference endotoxic LPS derived from Escherichia coli or Fusobacterium nucleatum. But the test fractions neither showed the activity to prepare rabbit skin to the local Shwartzman reaction, nor reacted with anti-lipid A conventional and monoclonal antibodies. Furthermore, unlike LPS, these fractions stimulated the splenocytes of C3H/HeJ mice (LPS-Nonresponder). Although the fractions showing the above biological activities have not yet been adequately purified, they contained polysaccharides, whose main constituent sugar is mannose with a smaller amount of arabinose, fatty acids consisting primarily of palmitic, stearic, and tuberculostearic acids, and small amounts of peptides and amino sugars. Since components characteristic of known immunomodulators of bacterial origin, namely endotoxins (lipid A's), cell wall peptidoglycans, lipoteichoic acids, cord factors (trehalose dimycolates), or deoxyribonucleic acids, were practically not detected in these fractions, the agent responsible for the above bioactivities is considered to be a novel substance different from the known, bacterial immunomodulators.

Adjuvants, Immunologic↗
PubMed1987

Monophasic and biphasic synovial sarcoma. An immunohistochemical study.

Seven cases of synovial sarcoma (SS), two with biphasic and five with monophasic histology, were studied immunohistochemically using monoclonal antibodies to intermediate filaments, keratin, and vimentin. Slender spindle cells and plump cells were constant components of all the tumors. Epithelioid cells were present only in biphasic SS. Epithelioid cells and plump cells were positively stained by both keratin and vimentin. Slender spindle cells were stained positive for vimentin and negative for keratin. Staining manner of each cell type was similar irrespective of monophasic or biphasic pattern. Present immunohistochemical studies suggested that monophasic or biphasic patterns in SS should be regarded as a different expression of the same disease. In addition, immunohistochemistry proved to be a useful tool to detect plump cells which were difficult to find on routine staining.

Adolescent↗
PubMed1987

Requirement of a properly acylated beta(1-6)-D-glucosamine disaccharide bisphosphate structure for efficient manifestation of full endotoxic and associated bioactivities of lipid A.

Several synthetic acylated glucosamine monophosphates, with structures corresponding to the nonreducing or reducing moiety of the lipid A of the Escherichia coli or Salmonella minnesota type, and a synthetic compound corresponding to a biosynthetic disaccharide lipid A precursor (designated Ia or IVA) were examined for their endotoxic and related bioactivities in comparison with those of the synthetic and bacterial parent molecules, i.e., acylated beta(1-6)-D-glucosamine disaccharide bisphosphates. Some of the test monosaccharide compounds were definitely active in most of the in vitro assays. Their activities, except for complement activation, however, were weaker than those of the reference compounds, synthetic and bacterial acylated disaccharide bisphosphates. The differences between the test monosaccharide and disaccharide compounds were much more apparent in in vivo assays, in which the test acylated glucosamine monophosphates were scarcely active, though some test compounds exhibited weak lethal toxicity in galactosamine-loaded mice and were weakly active in pyrogenicity, immunoadjuvant activity, and possible tumor necrosis factor and alpha and beta interferon-inducing ability in Mycobacterium bovis BCG- and Propionibacterium acnes-primed mice, respectively. Mixture at an equimolar ratio of acyl glucosamine monophosphates, each of which has the structure of the reducing or nonreducing moiety of the reference disaccharide compound, did not restore the endotoxic or associated bioactivities of the corresponding parent molecules. No essential differences in bioactivity were noted between synthetic and bacterial monosaccharide compounds, i.e., lipid X, whose structure corresponds to the reducing moiety of E. coli-type lipid A.

Acylation↗
PubMed1987

Development of cartilage-like tissue from androgen-dependent Shionogi carcinoma 115 in androgen-depleted hosts.

Androgen-dependent Shionogi carcinoma 115 (SC115) is an undifferentiated medullary carcinoma showing a compact cell pattern. When SC115 was inoculated into castrated DS mice, slowly growing tumors containing cartilage-like tissue developed. The cartilage-like tissue showed close similarities in electron microscopical and histochemical features to normal cartilage tissue. The origin of the cartilage-like cells was investigated by using the electrophoretic pattern of 3-phosphoglycerate kinase (PGK, EC 2.7.2.3) as a marker. The original DS strain had B-type PGK, but we developed a congenic strain with A-type PGK. The SC115 tumor, which had B-type PGK, was grafted into castrated congenic mice with A-type PGK. The cartilage-like tissue that developed was divided into two parts; one part was used for PGK analysis and the other for histological examination. All histologically confirmed cartilage-like tissues had only B-type PGK, suggesting that SC115 cells may change into cartilage-like cells in androgen-depleted conditions.

Androgens↗
PubMed1987

Isolation and characterization of an amphipathic antigen from Corynebacterium diphtheriae.

Amphipathic antigen was isolated from Corynebacterium diphtheriae Park-Williams number 8 cells by extraction with 47.5% phenol, nuclease treatment and gel filtration on Sepharose 6B. The chemical composition of the amphipathic antigen was hexose (73.8%), pentose (4.6%), fatty acids (9.8%) and glycerol (4.5%). The amphipathic antigen contained arabinose and mannose as sugars at a molar ratio of 1:6 and the major fatty acids were palmitic (C16:0) acid and palmitoleic (C16:1) acid (64.2% and 26.2%, respectively). The amphipathic antigen sensitized sheep erythrocytes and had definite immunobiological activities: viz mitogenic activity on murine splenocytes, stimulatory activity on guinea pig peritoneal macrophages and human complement activation. Deacylation of the amphipathic antigen with alkali treatment lost the sheep erythrocyte-sensitizing ability and some immunobiological activities. The isolated amphipathic antigen described is not a lipoteichoic acid and is different from the teichoic acid of C. diphtheriae.

Amino Acids↗
PubMed1986

Differential effects of type I IFN and IFN-gamma on the binding of tumor necrosis factor to receptors in two human cell lines.

The effect of IFN-alpha and IFN-beta on the expression of cell surface receptors for tumor necrosis factor (TNF) was examined in two human cell lines. In HeLa cells, IFN-alpha and IFN-beta increased 125I-TNF binding, whereas in HT-29 cells these two IFN either slightly decreased or had no effect on 125I-TNF binding. In contrast, IFN-gamma increased 125I-TNF binding in both cell lines. Both IFN-alpha and IFN-beta exerted an antagonistic effect on IFN-gamma-induced stimulation of TNF receptor expression in HT-29 cells, but did not inhibit TNF receptor induction by IFN-gamma in HeLa cells. IFN-gamma and, to a lesser extent, IFN-beta were synergistic with TNF in producing cytotoxic/cytostatic activity in HT-29 cells. Despite the inhibitory effect of IFN-beta on the IFN-gamma-induced stimulation of TNF receptor expression, IFN-beta did not inhibit the synergistic enhancement of TNF cytotoxicity by IFN-gamma in HT-29 cells. The dissociation between the effects of IFN-beta on TNF receptor expression and on the cytotoxic activity of TNF in HT-29 cells suggests that TNF receptor modulation is not a major mechanism of synergism between IFN and TNF.

Cell Cycle↗
PubMed1986

Tumor necrosis factor provokes superoxide anion generation from neutrophils.

We report that tumor necrosis factor (TNF) provokes superoxide anion generation from human neutrophils. Superoxide anion generation was provoked at TNF concentration of 1 X 10(-11) M and maximal generation was attained at TNF concentration of 1 X 10(-9) M. We also show that movements of intracellular calcium may mediate the TNF-stimulated superoxide anion generation because 8-(diethylamino) octyl 3,4,5-trimethoxybenzoate hydrochloride--but not extracellular EGTA--inhibited the generation of superoxide anion. These results suggest that TNF may mediate some mechanisms of host defense by provoking superoxide anion generation from neutrophils.

Calcium↗
PubMed1986

Tumor necrosis factor receptors in HeLa cells and their regulation by interferon-gamma.

Incubation of HeLa cell cultures with human interferon-gamma (IFN-gamma) increased the binding of radioiodinated human tumor necrosis factor (TNF) to specific cell surface receptors (TNF-R). IFN-gamma also produced a proportionate increase in receptor-mediated endocytosis of TNF. TNF-R expression was significantly increased after 6 h of exposure to IFN-gamma (100 units/ml), and it remained elevated in the continuous presence of IFN-gamma for at least 20 h. Incubation of cells with IFN-gamma in the presence of cycloheximide, followed by treatment with actinomycin D and reversal of the inhibition of protein synthesis, also resulted in increased TNF-R expression as compared to cultures subjected to the same treatments in the absence of IFN-gamma. These results suggest that IFN-gamma can directly stimulate accumulation of the mRNA for TNF-R and that TNF-R is among the cellular proteins whose synthesis is increased by IFN-gamma.

Cycloheximide↗