Search PubMed⌕ Search

Biomedical subjects

T Kishida

Publications and source records attributed to T Kishida.

At least 235 records · Page 13Linked to original sources

Direct and indirect effects of interferon on in vivo murine tumor cell growth.

We cloned two sublines (S1 and R1) of murine Meth A fibrosarcoma cells with respect to their sensitivity to a murine alpha/beta-interferon (IFN) preparation. The growth of S1 cells was suppressed and that of R1 cells was hardly affected by IFN in vitro. This was also the case with cells enclosed in cell-impermeable diffusion chambers in peritoneal cavities. Nevertheless, IFN suppressed the growth of not only S1 cells but also R1 cells in mice inoculated i.p. with these cells, and the survival rates of both S1 cell recipients and R1 cell recipients were markedly improved. S1 cells were observed microscopically to be injured by the direct effect of IFN in vitro and in vivo, but R1 cells in in vitro culture with IFN and those surviving in vivo in the presence of IFN appeared to proliferate well. In the peritoneal cavity of R1 recipients treated daily with IFN, the recruitment of macrophages was enhanced in comparison with untreated R1 recipients. Adherent peritoneal exudate cells obtained from IFN-treated, R1-bearing mice were highly suppressive for the in vitro growth of not only R1 cells but also allogeneic and human cells. The role of macrophages in the indirect effect of IFN on tumor cell growth is discussed.

Animals↗

Effect of low dosage of interferon on natural killer activity in patients with HBsAg-positive chronic active hepatitis.

The effect of human leukocyte interferon (IFN) on natural killer (NK) activity in 7 patients with HBsAg-positive chronic active hepatitis was investigated. Human leukocyte IFN was intramuscularly given once a week for 4 consecutive weeks (10 X 10(5), 5 X 10(5), 2 X 10(5) and 1 X 10(5) U). 1 week after the initial injection, NK activity showed a significant rise compared with the preinjection levels (p less than 0.001) and remained elevated during the 1-month treatment, while it fell after the cessation of IFN therapy. 4 of 5 patients showed a marked decrease in Dane particle-associated DNA-polymerase activity. Serum HBeAg disappeared in 3 of 6 patients and serum transaminase levels markedly improved in all patients. Only a transient reduction in HBsAg was observed in 2 patients after the treatment period. The findings indicate that a low dosage of human leukocyte IFN such as 18 X 10(5) U, administered in decreasing doses, enhances NK activity in patients with HBsAg-positive chronic active hepatitis, and that the effect of IFN is involved in the immune mechanisms associated with natural cytotoxicity.

Adult↗

Factor determining the antigenic type of interferons produced in human lymphoblastoid cell lines.

The factor that determines the antigenic type of IFN produced in human lymphoblastoid cell lines was examined using live Sendai virus, ultraviolet (UV)-irradiated virus, HANA spikes exposed on L cells persistently infected with Sendai virus (L-HVJ) and poly-inosinic acid poly-cytidylic acid (poly I: C). When Sendai virus was irradiated with UV-light for 300 sec, its abilities to infect chicken eggs and induce IFN were diminished, but its HA activity was unaffected. HANA spikes exposed on L-HVJ could not induce IFN in human lymphoblastoid cell lines, although they induced IFN in mouse spleen cells. These results suggest that the induction of IFN in human lymphoblastoid cells is closely related to viral nucleic acid. Poly I: C also induced IFN in some human lymphoblastoid cell lines in which IFN production is induced by Sendai virus. The antigenic types of IFN induced by poly I: C were the same as those induced by Sendai virus. These results suggest that the antigenic type of IFN produced depends on the nature of the IFN producer cells rather than on the kind of IFN inducer.

Animals↗

[Current problems on interferon research].

The Interferon is a biological response modifier (BRM) rather than a antibio-chemotherapeutic substance. Or, in other words, it may be a member of "hormonal immune interferon prostaglandin (HIIP)" multisystem in animal body. The author wishes to pick up the problems on clinical researches of human interferons (alpha, beta and gamma type) from the view point of BRM. So, main theme is the optimal posology and combined method of interferons and other therapies in viral diseases and especially on cancer patients.

Animals↗

Interferon counteracts pyrimidinone-induced hyporeactivity and the combined treatment has antitumor effect in mice.

A potent interferon (IFN) inducer, 2-amino-5-bromo-6-phenyl-4-pyrimidinone (ABPP), induced hyporeactivity in mice, and so IFN induced by subsequently administered ABPP was reduced even 120 hr after the first administration of ABPP. This hyporeactivity was counteracted by the injection of IFN (10,000 IU or more) 3 hr before the subsequent administrations of ABPP. Since the injection of more than 5,000 IU/mouse of IFN 3 hr before an administration of ABPP enhanced the circulating IFN titer, the priming effect in vivo by IFN may result in the reduction of hyporeactivity. Administrations of ABPP (200 mg/kg or 500 mg/kg) at intervals of 2 days and the injection of IFN (25,000 IU/mouse) 3 hr before each administration of ABPP to neuroblastoma-bearing A/J mice reduced the mortality and completely cured 40% of the mice in each combined therapy group. These results suggest that the combined use of the IFN inducer with IFN may be available for patients with neoplasm or viral infection.

Animals↗

[Trial of purifying tumor degenerating factor of human fibroblasts].

Tumor-degenerating factor (TDF) with the specific activity of 2.9 units/mg of protein was produced and purified by several chromatographies. The specific activity was increased to 302 units/mg of protein by DEAE-Sephadex A-50 chromatography, repeated twice. Then, this preparation was purified to the specific activity of 2,040 units/mg of protein with recovery rate of 16.6% by Con A-Sepharose and CM-Sephadex C-50 chromatographies. Finally, the specific activity was increased to 9,010 units/mg of protein with the final recovery rate of 14.6% by Blue Sepharose CL-6B chromatography.

Cell Transformation, Neoplastic↗

Reduced resistance to experimental viral and bacterial infections of mice treated with polychlorinated biphenyl.

When mice given diet containing 100, 200 or 400 micrograms of polychlorinated biphenyl (PCB) per g, or PCB-free diet for 21 days were inoculated intranasally with influenza virus, the mortality was higher in some groups given PCB than in the control group. When Staphylococcus aureus was inoculated intraperitoneally into mice given a diets with or without PCB, a significant difference was observed in the mortalities in the groups. Subcutaneous injection of S. aureus also caused a larger subcutaneous abscess in the mice given diets containing PCB than in those given control diet. Thus, it is suggested that PCB ingestion reduces host resistance to systemic or local infection with viruses or bacteria.

Administration, Oral↗

Identification of human blood with hybridoma-derived antibody to human immunoglobulin G.

During production of monoclonal anti-Gamma (Gm) antibody by the hybridoma technique, an antihuman immunoglobulin G (IgG) antibody was obtained. Unlike conventional antihuman IgG heteroantisera, this antibody reacted with the serum of humans and chimpanzees but did not cross-react with that of other primates or lower animal species in hemagglutination-inhibition tests with anti-D-coated red cells. To examine for the practical utility of the antihuman IgG antibody in an enzyme-linked immunosorbent assay (ELISA) for identification of human blood, microtiter wells were coated with human IgG and allowed to react with the antibody in the presence of human or animal serum under test. The bound antibody was detected with enzyme labeled antimouse IgG. The ELISA gave satisfactory results.

Animals↗

Effect of human leukocyte interferon on malignant brain tumors.

The antitumor effect of human leukocyte interferon was investigated on ten patients with malignant brain tumor. In eight cases of primary tumor, IFN alone was administered when their recurrent sign was evident. A dose of 3 X 10(6) IU or 1 X 10(6) IU of IFN was injected intramuscularly two or three times a week in high-dose group, while a dose of 5 X 10(4) IU once a week in low-dose group. No remarkable side effects including bone marrow depression were noted. Natural killer activity was enhanced and immunologic skin reaction manifested. Partial remission of more than 50% decrease of tumor volume calculated on CT scan was seen in two cases in the low-dose group for about 3-6 months. Complete remission could not be obtained by IFN alone. Our pilot study has shown that IFN alone will not be effective against progressive malignant brain tumors by general administration. Further investigation should be carried out to improve the use of IFN therapy in malignant brain tumor.

Adolescent↗

The production of interferon-alpha and -beta by cloned human lymphoblastoid cells. Brief report.

In our previous study we found that the ARH 77 human B lymphoblastoid cell line, originating from a patient with multiple myeloma, produced both human interferon-alpha (HuIFN-alpha) and HuIFN-beta after induction with Sendai virus. In order to examine whether IFN-alpha-producing ARH 77 cell clones can be separated from IFN-beta-producing ones, the ARH 77 line was cloned by the soft agar method. Twelve clones chosen at random were examined for IFN production and the antigenic types of IFN produced were determined. All examined clones simultaneously produced both HuIFN-alpha and HuIFN-beta, although the ratio of HuIFN-alpha to HuIFN-beta production was variable among the clones. This result suggests that one lymphoblastoid cell can produce both HuIFN-alpha and HuIFN-beta.

Cell Line↗

Prolongation by interferon preparation of the survival time of mice implanted with differentiation-inducible mouse myeloid leukemia cells.

The effect of L-cell interferon (IFN) preparation on the survival times of mice implanted with two different clones (T-22 and R-4) of mouse myeloid leukemic M1 cells were examined. T-22 cells, but not variant R-4 cells, can be induced to differentiate in vitro or in vivo into macrophages and granulocytes. In vitro growth of R-4 cells was markedly suppressed by IFN, but that of T-22 cells was resistant to IFN. The survival times of mice with implanted T-22 cells were prolonged by treatment with IFN but those of mice with implanted R-4 cells were not.

Animals↗

Effect of anti-interferon serum of influenza virus infection in mice.

Mice were infected by an aerosol of influenza virus Type A (0.5 LD50) and subsequently treated with 4 intranasal instillations of anti-interferon antiserum over a period of 72 h. All the mice treated with antiserum died within 7 days post-infection, whilst the mice in the control groups survived. In mice that did not receive the antibody, virus titers in the lung peaked on day 3 and then decreased again. Also, interferon was detectable both in lung homogenates and serum. In mice treated with antiserum, no interferon was detectable and the virus concentrations in the lung increased until death. These results suggest that interferon produced in the respiratory tract plays an important role in the early stages of influenza virus infection.

Animals↗

Mode of protection of mice against herpes simplex virus type 2 infection by Propionibacterium.

We compared various strains of Propionibacterium with regard to protection of young adult mice against lethal infection with herpes simplex virus type 2 (HSV-2). Propionibacterium acnes, P. granulosum, and P. avidum were protective, while P. acidi-propionici and P. lymphophilum were ineffective. The protective effect proved to be in the cell wall fraction. Attempts were made to elucidate possible mechanisms of the protection using both effective and ineffective strains. The results strongly suggest that induction of interferon rather than activation of macrophages and natural killer cells by Propionibacterium pretreatment plays a crucial role, directly or indirectly, in protection against infection by herpes simplex virus. Propionibacterium only moderately protected newborn mice against HSV-2 infection.

Adjuvants, Immunologic↗

Studies on biological actions of dimethyl sulfoxide in familial amyloidosis.

DMSO was therapeutically administered to patients with FAP and in about half of the patients there was some clinical improvement. Urinary proteins were analyzed biochemically and immunochemically before and after DMSO administration in seven cases of amyloidosis. As the results, increased excretion of various proteins of different molecular weights in the urine was observed depending on cases and examined organs. The in vitro effects of DMSO on amyloid proteins were examined. DMSO-degraded amyloid proteins showed void-volume materials and lower molecular weight components on Sephadex G column elution profiles as did guanidine-degraded amyloid protein. Among various denaturating or reducing agents, DMSO is the least potent in dissolving amyloid fibrils into prealbumin-related proteins.

Adult↗

Therapeutic effect of a low dosage of human leukocyte interferon on chronic hepatitis B virus infection.

A low dosage of human leukocyte interferon was intramuscularly given to 47 patients with hepatitis B surface antigen (HBsAg) positive chronic active hepatitis once a week for 4 consecutive weeks (10 X 10(5), 5 X 10(5), 2 X 10(5) and 1 X 10(5) U). After treatment, a reduction of serum HBsAg was observed in 26 patients; 3 of them showed no serum HBsAg and 1 of the 3 appeared to produce antibody to HBsAg. 31 of 34 patients investigated showed a significant decrease in Dane particle-associated DNA-polymerase activity (p less than 0.001). Among 17 patients positive for hepatitis B e antigen (HBeAg), 10 of them seroconverted to anti-HBe. Serum transaminase levels also significantly improved in 34 of 38 patients (p less than 0.001). Our findings indicate that a low dosage of human leukocyte interferon such as 18 X 10(5) U, administered in progressively decreasing doses, may be effective in the treatment of chronic hepatitis B virus infection.

Adult↗