Biomedical subjects

Y Horisawa

Publications and source records attributed to Y Horisawa.

11 recordsLinked to original sources

PubMed1989

In vivo antitumor mechanism of natural human tumor necrosis factor involving a T cell-mediated immunological route.

We have investigated the in vivo antitumor mechanism of natural human tumor necrosis factor (n-TNF) isolated from a culture of human leukemic B cell line (BALL-1), especially its action as an immunomodulator, and found that the in vivo antitumor effect of n-TNF on Meth A sarcoma implanted in BALB/c mice pretreated with monoclonal antibody against T cell-specific surface antigen (Thy-1) was significantly diminished. Furthermore, when BALB/c mice were treated with T cell subset-specific monoclonal antibodies, anti-L3T4 or anti-Lyt-2.2, the antitumor effect of n-TNF on Meth A sarcoma was significantly reduced. Therefore, it was suggested that the in vivo antitumor mechanism of n-TNF might involve a T cell-mediated immunological route.

Animals↗

PubMed1988

Deferoxamine mesylate inhibits bacterial growth in vivo.

Iron is one of the essential element for bacterial growth. To study the effect of chelation of iron on bacterial growth, 17 different strains of bacteria were cultured in chocolate-agar medium in the presence or absence of deferoxamine methylate (DM), a potent chelating agent for iron. A fairly low concentration of DM (10 mg/ml) in the culture medium markedly inhibited the growth rates of the three bacterial strains, B. catarrhalis, N. meningiditis and N. gonorrhoeae. In vivo effect of DM was also tested in mice that were intraperitoneally inoculated with a lethal number of N. meningiditis (2 x 10(8)/animal). After 40 h of inoculation, more than 90% of the control animals died for acute peritonitis. In contrast, animals which were intraperitoneally administered with DM showed a marked resistance to the inoculated bacteria without showing toxic effects of the agent: less than 30% of animals died of acute peritonitis caused by infection within 40 h. The results suggest that, in addition to the currently used antibiotics. DM might also be an useful therapeutic agent for treatment of bacterial infection.

Animals↗

PubMed1987

The inhibition of neoplastic cell proliferation with human natural tumor necrosis factor.

Purified human natural tumor necrosis factor (n-TNF) was prepared by stimulating human leukemic B cell line (BALL-1) with Sendai virus. The colony formations of all of 18 human cancer-derived abnormal cell lines were suppressed by 10(1)-10(6) U/ml of n-TNF, while n-TNF was nontoxic to all human normal fibroblast cells. This in vitro inhibition of cell growth was reversible. In breast adenocarcinoma MCF7 cells treated with n-TNF a specific decrease of DNA synthesis was observed, and DNA histograms showed a block at G1 in the cell cycle. In vivo studies revealed that n-TNF suppressed the tumor growth of murine Meth A sarcoma, human renal adenocarcinoma (ACHN), malignant melanoma (SK-MEL-28) and glioblastoma (U-373 MG). Isobologram analysis showed that n-TNF synergistically inhibited cell growth in combination with human natural interferon (IFN)-a. In vivo synergism of n-TNF and IFN-a was also found in the U-373 MG tumor model implanted into nude mice.

Animals↗

PubMed1986

[Basic study on human interferon-beta: Part III. The mechanisms of its antitumor effect].

The mechanisms of the direct and indirect antitumor effects of human interferon-beta (IFN-beta, MR-21) were examined. IFN-beta suppressed DNA, RNA and protein synthesis in cells derived from human tumor. The expression of cellular oncogenes (c-Ha-ras and c-myc) in tumor-originated cells was also suppressed by IFN-beta. These results suggest that such suppression is one possible mechanism of the direct anticellular effect induced by IFN-beta. IFN-beta augmented NK cell activity and the ADCC activity of human peripheral blood lymphocytes. It is also suggested that these are two of the immune system-mediated mechanisms responsible for the indirect antitumor effect of IFN-beta in vivo.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1986

[Concentrations of cefmenoxime in human bone marrow blood and osseous tissue].

One gram of cefmenoxime (CMX) was administered to each of 10 patients by a one shot intravenous injection at the beginning of surgery. At 30, 60, 90, 120 minutes after the administration, concentrations of CMX in venous blood, bone marrow blood and bone tissue were assayed by the agar-well method. CMX was smoothly transmigrated after the injection from venous blood to bone marrow blood and bone tissue, and effective concentrations higher than MIC80 values were maintained for several hours. CMX, therefore, appears to be a useful drug for the prophylaxis and the treatment of postoperative infections.

Adult↗

PubMed1986

[Basic study on human interferon-beta: Part I. Antiviral effect].

A study was performed on the antiviral effects of human interferon-beta (IFN-beta, MR-21) produced by a normal human diploid fibroblast cell strain. Of 4 DNA and 9 RNA viruses used in this study, all were inhibited by the IFN-beta and the IC90S obtained were approximately 10(1)-10(3) IU/ml. Results showed that IFN-beta had a very wide antiviral spectrum. The IFN-beta was able to induce 2',5'-oligo A synthetase activity in RSa, HeLa S3 and M08 cell lines but not in HEC-1C cell line lacking receptors for IFN-beta. This strongly suggests that one of the antiviral mechanisms might function through the induction of 2',5'-oligo A synthetase activity through the IFN-beta receptor.

2',5'-Oligoadenylate Synthetase↗

PubMed1986

[Basic study on human interferon-beta: Part II. Anticellular effect].

The anticellular effect of human interferon-beta (IFN-beta, MR-21) was examined in vitro. IFN-beta had a wide anticellular spectrum in proliferation inhibition assay. Of 67 human cell lines including 62 tumor-originated cell lines, 51 were sensitive to IFN-beta (IC50 less than 1,000 IU/ml) while 16 including normal diploid cells were resistant (IC50 greater than or equal to 1,000 IU/ml). These anticellular effects were reversible and there was no relationship between the origins of tumor cell lines and their sensitivity to IFN-beta. IFN-beta induced not only proliferation inhibition but also cytotoxicity in several cell lines. It was suggested that the mode of anticellular effects of IFN-beta was mainly time-dependent.

Cell Count↗

PubMed1986

[Basic study on interferon-beta: Part IV. Antitumor effect on nude mouse-transplanted human tumors].

The effects of human interferon-beta (IFN-beta, MR-21) on the growth of xenografted human tumors in nude mice were examined. IFN-beta was administered to mice with malignant melanoma (SK-MEL-28 and Sk-14) intratumorally at a dose of 1 X 10(5)-3 X 10(5) IU/mouse, with acute leukemia (CCRF-HSB-2) intratumorally at a dose of 3 X 10(5) IU/mouse, with glioblastoma (U-373 MG) intravenously or intratumorally at a dose of 1 X 10(5)-6 X 10(5) IU/mouse, or with uterine cervical tumor (HeLa S3) intravenously at a dose of 0.3 X 10(5)-1 X 10(5) IU/mouse. IFN-beta inhibited the growth of all of these tumors in a dose-dependent manner.

Acute Disease↗

PubMed1986

[Study on human lymphoblastoid interferon-alpha (MOR-22): Part III. Antitumor effect on nude mouse-transplanted human tumors].

The effects of human lymphoblastoid interferon-alpha (MOR-22) on the growth of xenografted human tumors in nude mice were examined. IFN-alpha was administered subcutaneously to mice with renal tumor (ACHN), intratumorally for glioblastoma (U-373MG) or intravenously with uterine cervical tumor (HeLa S3). The dosages of IFN-alpha were 2 X 10(4)-5 X 10(5) IU/mouse for ACHN tumor, 1 X 10(5)-5 X 10(5) IU/mouse for U-373MG tumor and 3 X 10(4)-1 X 10(5) IU/mouse for HeLa S3 tumor. IFN-alpha inhibited the growth of these tumors in a dose-dependent manner.

Animals↗

PubMed1986

[Basic study on human lymphoblastoid interferon-alpha (MOR-22): Part I. Antiviral effect].

A study was performed on the antiviral effects of human interferon-alpha (MOR-22) produced by a human lymphoblastoid cell line (BALL-1). Of 4 DNA and 9 RNA viruses used in this study, all were inhibited by the IFN-alpha and the IC90s obtained were 10(1)-10(4) IU/ml. Results showed that IFN-alpha had a very wide antiviral spectrum. The IFN-alpha was able to induce 2',5'-oligo A synthetase activity in RSa, HeLa S3 and M08 cell lines but not in a HEC-IC cell line lacking receptors for IFN-alpha. This strongly suggests that one of the antiviral mechanisms might function through the induction of 2',5'-oligo A synthetase activity through the IFN-alpha receptor.

2',5'-Oligoadenylate Synthetase↗

PubMed1986

[Study on human lymphoblastoid interferon-alpha (MOR-22): Part II. Anticellular effects].

The direct and indirect anti-cell proliferation effects of IFN-alpha produced by BALL-1 cells were examined. Of 23 cell lines, 7 including 2 normal diploids were resistant to a dose 1000 IU/ml of IFN-alpha. On the other hand, 16 cell lines were sensitive and showed IC50 values of less than 1000 IU/ml. This anti-cell proliferation spectrum showed no specificity to tumor origin and its activity was reversible. Cellular oncogene expression was markedly suppressed by IFN-alpha treatment. This finding showed that there might be some correlation between anti-cell proliferation activity and anti-oncogene expression activity. Furthermore, by activating natural killer cell activity and antibody dependent cell-mediated cytotoxicity, IFN-alpha potentiated indirect anti-cell activity.

Antibody-Dependent Cell Cytotoxicity↗