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Biomedical subjects

Y Niitsu

Publications and source records attributed to Y Niitsu.

At least 307 records · Page 17Linked to original sources
PubMed1986

Release of tumor necrosis factor (TNF) into mouse peritoneal fluids by OK-432, a streptococcal preparation.

A cytotoxic factor was induced in peritoneal fluid by injection of OK-432 in mice which had been primed with OK-432. Two-step stimulation (priming and eliciting) was always necessary to induce the cytotoxic factor. OK-432-primed mice did not produce soluble cytotoxic factor spontaneously and no cytotoxic activity was detected in the mice treated by a single injection of OK-432 as an eliciting agent. This observation was also confirmed by in vitro experiments. Only when activated macrophages were incubated with OK-432 (or with lipopolysaccharide) was cytotoxin released into medium supernatant. High doses of OK-432 were required to prime mice for the production of cytotoxic factor, whereas a small amount was enough to elicit. The peritoneal cytotoxic factor obtained by OK-432 injection appears to be identical to tumor necrosis factor in the serum for the following reasons: The two factors are similar in mode of cytotoxic action. Both are produced from macrophages. They are similar in physicochemical characteristics. The cytotoxicity of the peritoneal cytotoxic factor was totally abolished by anti-TNF serum.

Animals↗
PubMed1986

Characterization of a cytotoxic factor induced in mouse peritoneal fluid by OK-432.

A cytotoxic factor (peritoneal cytotoxic factor, PCF) was strongly induced by the injection of LPS into the peritoneal fluids of mice which had been previously primed with OK-432. In order to clarify characteristics of PCF, physicochemical and immunological studies were conducted. When incubated with LPS, the macrophages from mice primed with OK-432 induced PCF whereas the lymphocytes did not. These results indicate that PCF is different from lymphotoxin. PCF appears to be quite similar to tumor necrosis factor (TNF) in the serum for the following reasons: The two factors are similar in the mode of cytotoxic action in vitro; both factors have a tumor necrotizing effect when injected into tumor bearing mice; both are produced from macrophages; they are similar in physicochemical characteristics; and the cytotoxic activity of PCF is totally abolished by anti-TNF serum.

Animals↗
PubMed1986

Circulating transferrin receptor in human serum.

Circulating transferrin receptor has been detected in human serum with a sensitive immunoassay. The mean concentrations of the serum transferrin receptor in healthy males and females were 251 +/- 94 (mean +/- SD) ng/ml and 256 +/- 99 ng/ml, respectively. The serum receptor concentration in patients with haematological malignancies, including acute leukaemia, multiple myeloma and malignant lymphoma, varied widely, from normal to 1100 ng/ml. A single band with an approximate molecular weight between 80,000 and 100,000 daltons was obtained by polyacrylamide gel electrophoresis-immunoblotting analysis of serum.

Acute Disease↗
PubMed1986

Therapeutic effect of endogenous tumor necrosis factor on ascites Meth A sarcoma.

The therapeutic effect of endogenous tumor necrosis factor (TNF) on Meth A ascites fibrosarcoma in mice was investigated. Serum and peritoneal fluid from tumor bearing mice treated with OK-432 and LPS were cytotoxic to tumor cells in vitro. The peak of cytotoxicity in both the serum and peritoneal fluid was found in the fraction corresponding to a molecular weight of approximately 54,000-56,000 on HPLC and the pI was found to be 4.9-5.1 by isoelectric focusing. These results are consistent with previously reported findings on TNF, and indicate that endogenous TNF has a satisfactory life-prolonging effect. The tumor necrosis factor (TNF) is considered to be one of the clinically most promising anti-cancer cytokines because of its potent and very specific antitumor effect on target cells (Carswell, Old, Kassel, Green, Fiore & Williamson, 1975; Matthews & Watkins, 1978; Niitsu, Watanabe & Urushizaki, 1984). TNF as an anti-cancer cytokine for the treatment of cancer may be applied in one of the two following ways: by administration of purified TNF or by endogenously inducing TNF in cancer bearing individuals. The antitumor effects of TNF administered exogenously have been examined using crude preparations or serum containing TNF (tumor necrosis serum, TNS) (Carswell et al., 1975; Watanabe, Niitsu, Sone, Neda, Ishigaki & Urushizaki, 1984). In a previous paper we reported that mice primed with OK-432 and challenged with endotoxin produced a soluble cytotoxic factor in peritoneal fluids (Yamamoto, Nagamuta, Usami, Sugawara, Watanabe, Niitsu & Urushizaki, 1985; Nagamuta, Yamamoto, Usami, Sugawara, Watanabe, Niitsu & Urushizaki, 1985). Ths peritoneal cytotoxic factor (PCF) had cytostatic and/or cytotoxic effect not only on mouse tumor cell lines but also on human tumor cell lines without species specificity. Normal cell lines were not affected. Here we report the endogenous production of TNF in tumor bearing mice and its antitumor effects.

Animals↗
PubMed1986

[Anti-tumor effect and the mechanism of action of human recombinant TNF].

TNF is cytokine derived from macrophages and holds strong promise for application to cancer therapy because of its marked antitumor effects and its high specificity to tumors. The clinical application (Phase I-II) of TNF has been started because human recombinant TNF (rH-TNF) can been produced on a large scale. In spite of notable antitumor effects, little is known concerning the mechanism of action of its cytotoxic activity. In this article, the antitumor effects of rH-TNF against human and murine tumors, the mechanism of its action and the synergistic effects of rH-TNF in combination with IFN-gamma or with cyclophosphamide are reviewed.

Adult↗
PubMed1986

[Analysis of the TNF receptor in KYM cells by affinity cross-linking].

We investigated the identity of the TNF receptor on the KYM cell membrane by cross-linking 125I-TNF and the presumed receptor site with DSS, and subjecting the TNF-receptor complex to electrophoresis. Four specific bands were observed at 145 K, 50 K, 35 K, and 17 K, and those at 50 K, 35 K and 17 K being consistent with trimers, dimers and monomers of TNF, respectively. The 145 K band disappeared after addition of excess unlabelled TNF or anti-human recombinant TNF monoclonal antibody (IV3-E), which quenched the cytotoxic activity of TNF and inhibited the TNF binding to the receptor. The molecular weight of native TNF as estimated by gel filtration was 45 K and this observation showed that native TNF existed only as the TNF trimer. These results confirmed that 95K, i.e., the difference between 145 K and 50 K, is the molecular size of the TNF receptor.

Antibodies, Monoclonal↗
PubMed1986

[Analysis of TNF receptor by binding assay].

The existence of a TNF receptor on TNF-sensitive tumor cells and on certain normal cells was elucidated by specific binding assay. A close correspondence (r = 0.855) was shown between the receptor number and the sensitivity of the tumor cells. However, for normal cells, despite the existence of TNF receptors, no cytotoxic effect was observed. Furthermore, certain normal diploid cells underwent proliferation as a result of TNF stimulation. It was therefore concluded that the existence of TNF receptor is essential but not sufficient in itself for TNF-induced cytotoxicity.

Animals↗
PubMed1986

[Induction of a cytotoxic factor into the peritoneal fluid (PCF) by OK-432. II. Physicochemical and immunological characteristics of PCF].

A cytotoxic factor (PCF = peritoneal cytotoxic factor) was strongly induced by the injection of LPS into the peritoneal fluids of mice which had been previously primed with OK-432. The similarity in biological activity of PCF, TNF and lymphotoxin led us to study the relationships among the three. When incubated with LPS, the macrophages from the mice primed with OK-432 induced PCF, whereas the lymphocytes did not. These results indicate that PCF is different from lymphotoxin. PCF appears to be identical to Tumor Necrosis Factor (TNF) in the serum for the following reasons: The two factors are similar in their modes of cytotoxic action in vitro. Both factors have a tumor-necrotizing effect when injected into tumor-bearing mice. Both are produced from macrophages. They are similar in their physicochemical characteristics. The cytotoxic activity of PCF was totally abolished by anti-TNF serum.

Animals↗
PubMed1986

[Production of a cytotoxic factor in mouse peritoneal fluid by OK-432, a streptococcal preparation].

A cytotoxic factor was induced by the injection of LPS into the peritoneal fluids of mice which had been previously primed with a streptococcal antitumor preparation, OK-432. No cytotoxic effect on L-929 cells was observed in the peritoneal fluids of mice singly treated with OK-432 or LPS. Various mouse and human tumor cell lines were effectively killed by this peritoneal cytotoxic factor, though normal cell lines were insensitive, which indicates that this factor is not species-specific. The highest level of cytotoxic activity was obtained when LPS was given to mice 5 days after the injection of OK-432. The optimal time for collection of peritoneal fluids for the cytotoxic factor was 2h following the LPS injection. Interferon activity was found to be negative by the plaque reduction test using L-929 cells with vesicular stomatitis virus.

Animals↗
PubMed1986

[Induction of mouse peritoneal cytotoxic factor by OK-432. (3). Comparison between LPS and OK-432 as eliciting agents].

By injection of OK-432, a cytotoxic factor was induced in peritoneal fluids of mice which had been primed with OK-432. Two-step stimulation (priming and eliciting) was always necessary to induce the cytotoxic factor. OK-432-primed mice did not produce soluble cytotoxic factor spontaneously and no cytotoxic activity was detected in the mice treated by a single injection of OK-432 as an eliciting agent. High doses of OK-432 were required to prime mice for the production of cytotoxic factor, whereas a small amount was enough to elicit it. Pathological studies were also conducted in order to clarify whether the mice were safe under the conditions in which PCF had been induced. Moderate liver damage was observed in the mice injected with OK-432 and LPS, whereas no histological change in the liver or spleen was observed in the mice treated with OK-432 alone. These results suggest that OK-432 is a good candidate as an inducer of cytotoxic factor in the peritoneal cavity.

Animals↗