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Biomedical subjects

I Takashima

Publications and source records attributed to I Takashima.

149 records · Page 9Linked to original sources

Immunological properties of tumor cells genetically modified to secrete interleukin-2.

The immunological properties of interleukin-2 (IL-2) gene-transduced tumor cells were investigated in mice. A murine ovarian cancer cell line, OVHM, was retrovirally transduced with the human IL-2 gene (OVHM/IL-2) and the neomycin resistance gene (OVHM/Neo). OVHM/IL-2 cells continuously secreted IL-2 detected by ELISA using an antibody specific for human IL-2, and by a bioassay using an IL-2-reactive cell line (CTLL-2). When OVHM cells were inoculated subcutaneously into syngeneic B6C3F1 mice, OVHM/IL-2 cells but not parental (OVHM/P) or OVHM/Neo cells were regressed even though their rate of in vitro growth was comparable. This was not observed in nude mice, indicating the involvement of T lymphocytes in the regression of OVHM/IL-2 cells. The survival of mice inoculated intraperitoneally with OVHM/IL-2 cells was prolonged compared with those inoculated with OVHM/P cells. In irradiation experiments, IL-2 secretion by irradiated OVHM/IL-2 cells was retained for at least 5 days, although in vitro growth and in vivo tumorigenicity of irradiated OVHM/IL-2 cells were completely diminished. When mice were challenged with viable OVHM/P cells, survival of mice previously immunized with irradiated OVHM/IL-2 cells was prolonged compared to those immunized with irradiated OVHM/P cells, indicating a vaccine property of irradiated OVHM/IL-2 cells. Moreover, survival of mice with established ascites was improved upon injection of irradiated OVHM/IL-2 cells, indicating a therapeutic potential of OVHM/IL-2 cells. Tumor cells genetically engineered to secrete IL-2 may therefore be promising candidates for tumor vaccines and may provide a new mode of cancer immunotherapy.

Animals↗

Labeled avidin-biotin enzyme-linked immunosorbent assay for detecting antibody to infectious laryngotracheitis virus in chickens.

A labeled avidin-biotin enzyme-linked immunosorbent assay (LAB-ELISA) for detecting antibody to infectious laryngotracheitis (ILT) virus in chicken sera was developed and compared with ordinary ELISA. Purified ILT virus, biotin-labeled anti-chicken IgG rabbit IgG conjugate, and horseradish-peroxidase-labeled avidin were used in the LAB-ELISA. When sera from farm chickens were tested by serum neutralization (SN) and two kinds of ELISA, the correlation rate between SN and LAB-ELISA was 50/50 (100%), and that between SN and ordinary ELISA was 39/50 (78%). In LAB-ELISA, all of the sera that were antibody-negative by SN had low absorbance (A) values (below 0.05), and the A values were closely correlated with the SN indexes. In ordinary ELISA, however, the sera antibody-negative by SN had various A values ranging from 0.06 to 0.32. LAB-ELISA had much lower nonspecific reactions than ordinary ELISA against sera from ILT-negative chickens, even when chickens were 30 weeks old. ILT antibody production after ILT vaccination could be detected by LAB-ELISA. A values peaked 5 weeks postinoculation and were maintained for 17 weeks.

Animals↗

Shedding and transmission of Chlamydia psittaci in experimentally infected chickens.

Three avian strains of Chlamydia psittaci were inoculated into 8-day-old chickens by the intra-air-sac or peroral route. Uninoculated chickens were kept as cagemates with the air-sac-inoculated birds. The air-sac-inoculated birds had systemic infection, and chlamydiae were detected frequently in the livers, lungs, jejunums, and colo-rectums at high titers (greater than or equal to 10(5.0) ELD50). All three groups of birds had intermittent and persistent shedding of chlamydiae into feces during the 28-day observation period. In the cagemates, organisms were detected first in the colo-rectum 3 days postexposure and later in the liver, but not in the lung. Limited infection was seen particularly in the colo-rectum of the cagemates and perorally inoculated birds. Antibody response was markedly higher in the air-sac-inoculated chickens than in their cagemates and the perorally inoculated birds. These findings suggest that the colorectum is an important target organ for C. psittaci infection in chickens and that it may be the main site from which the organisms are shed into feces of chickens.

Air Sacs↗

Defective natural killer activity in gastric cancer patients: possible involvement of suppressor factor receptor.

The mechanism of defective natural killer (NK) activity in gastric cancer patients was studied with respect to the soluble immune suppressor factor receptor on NK cells. Phycoerythrin (PE)-conjugated anti-CD8 and -CD16 antibodies were used for the determination of NK phenotype, and fluorescein isothiocyanate (FITC)-conjugated wheat germ agglutinin (WGA) was for the lymphocyte surface receptor of soluble immune suppressor factor (SISF). It was found that NK activity of peripheral blood lymphocytes (PBLs) isolated from gactric cancer patients decreased with tumor progression in spite of an increasing tendency of their CD16+ population. The WGA+ population of PBLs inversely increased in parallel with cancer progression and a significant negative correlation was found between NK activity and the WGA+ population. Two-color flow cytometry showed a significant increase of WGA+ cells in the CD8dim and CD16+ population in advanced cancer patients. It is suggested that an increase of surface receptors for SISF on NK cells may, in part, cause the diminished NK activity in gastric cancer patients.

Antibodies, Monoclonal↗

Locoregional immunotherapy of malignant ascites by intraperitoneal administration of OK-432 plus IL-2 in gastric cancer patients.

The clinical efficacy of intraperitoneal administration of OK-432 plus interleukin-2 (IL-2) for treating malignant ascites was evaluated in gastric cancer patients. Ten KE of OK-432 and 200,000 Jurkat units of IL-2 were intraperitoneally administered in tandem in the order given on alternate days at paracentesis. Of the 22 evaluable patients, 18 (81%) developed complete or partial responses, showing a cytologic disappearance of cancer cells and decrease of ascites. More than 50% of the patients obtained positive responses within 2 weeks after the initial administration of the drugs. Improvements of performance status and clinical symptoms such as abdominal fullness, followed by restoration of oral food intake and prolongation of survival time were observed in responders treated with OK-432 plus IL-2. Flow cytometric analysis demonstrated a predominant increase of the CD3+CD4+ cells, especially of the CD4+CD45RA- subset in the peritoneal cavity of the responders. Cytotoxicity assay after negative selection of the CD4+ cells with the antibody and complement revealed that the CD4+ subset possessed cytotoxic activity against autologous tumor cells. The results suggest that intraperitoneal administration of OK-432 plus IL-2 may not be only a practical but also an effective protocol for treating malignant ascites in gastric cancer patients.

Adult↗