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Biomedical subjects

Y Seto

Publications and source records attributed to Y Seto.

At least 145 records · Page 8Linked to original sources

Role of the spleen on immunosuppression in esophageal and gastric cancer.

To elucidate the role of the spleen on immunosuppression of gastric and esophageal cancer, suppressor cell activities of spleen cells (SCs), splenic vein lymphocytes (SVLs) and peripheral blood lymphocytes (PBLs) were investigated. Concanavalin-A induced suppressor cell (Con-AS) activity of SCs was significantly higher in patients with gastric cancer than in those with benign diseases. Higher Con-AS activity of SCs was observed in esophageal cancer patients with tumors located in the lower portion of the esophagus. In comparison with suppressor activities of SCs and SVLs, the decrease of the predominance of suppressor precursors in SCs and the increase of the spontaneously activated suppressor cells in SVLs were noted with the advance of the tumors. Culture supernatants from splenic adherent cells significantly induced suppressor cell activities as well as did sera from splenic venous blood. From these results, it is concluded that the generation of suppressor precursors in the spleen is dependent on the location of tumors and that the maturation of suppressor cells occurs in the spleen by factors released from splenic adherent cells, then migrates into the peripheral blood.

Adult↗

The effect of food dye and other environmental substances on the host defense reaction in mice in relation to virus infection.

Environmental substances were examined for their effect on interferon induction and delayed type hypersensitivity (DTH) responses in mice. Amaranth, safrole, phenacetin and nicotine suppressed the DTH response, and suppressed the serum interferon titers induced by virus infection. However, they did not affect the interferon titers which were induced by tilorone, a chemical inducer. The peak of interferon titer was 12 hours after infection with herpes simplex virus type 2 (HSV-2). Therefore, amaranth, safrole, phenacetin and nicotine were given to mice intraperitoneally 24 hours before, and 2 and 18 hours after infection with HSV-2. It was found that safrole and nicotine shortened the mean survival time of HSV-2 infected mice when they were given to mice 2 hours after virus inoculation. Amaranth and phenacetin showed similar effects. However it was not definite statistically. In biochemical and hematological tests, these four substances did not affect the functions of liver, kidney and carbohydrate metabolism in normal mice. These results suggest that substances which may often be taken into the body have the potential to affect the onset of virus infectious diseases as a result of the suppression of the host defense reaction.

Animals↗

[Comparative study of estrogen receptor assays between immunocytochemical assay using monoclonal antibody and the dextran- coated charcoal method].

Estrogen receptor (ER) was measured by the estrogen receptor-immunocytochemical assay (ER-ICA) using monoclonal antibody in 36 mammary carcinomas. Simultaneously, ER and progesterone receptor (PgR) were measured by the dextran coated charcoal (DCC) method. In ER-ICA, tumor cells with estrogen receptors were histologically observed. The proportion of ER-positive tumor cells among tumor tissues and the levels of staining intensity were also examined. Results were compared to those obtained by the dextran coated charcoal (DCC) method. Tumors were evaluated as ER-ICA-positive when they contained more than 10% ER-positive cells. ER at a level of more than 5.0 fmol/mg protein was evaluated ER-positive and PgR at more than 5.0 fmol/mg protein as PgR-positive by the DCC method. Twenty-one out of 24 ER-ICA-positive tumors were ER-positive by the DCC method, and 11 out of 12 ER-ICA-negative tumors were ER-negative by the DCC method. Correlation of ER-ICA and ER by the DCC method was 88.9%. There were 11 PgR-positive tumors, and all were included among ER-ICA-positive tumors which had a high proportion of ER-positive cells and high staining intensities.

Antibodies, Monoclonal↗

[Immune reactivities of lymphocytes from peripheral blood, regional lymph nodes and tumor-infiltrating lymphocytes in breast cancer].

Immune reactivities in 174 breast cancer patients were investigated. Immune reactivities were assessed by lymphocyte responsiveness to phytohemagglutinin (PHA), suppressor cell activities, sera-induced suppressor cell activities, NK activities and autologous tumor-killing activities. Low responsiveness of peripheral blood lymphocytes (PBL) to PHA mitogen and an increase in the inductive activity of suppressor cells by sera were observed in breast cancer patients as compared with normal volunteers or patients with benign breast diseases. These impairments of immune reactivities were compared with those of patients with cancer of the digestive tract. Cytotoxicities against both K562 and autologous tumor cells were low or absent in the regional lymph node lymphocytes (LNL). Cytotoxicities against autologous tumor cells were absent in tumor-infiltrating lymphocytes. The low NK activity of LNL was not due to coexistent suppressor cells but to a lack of active NK cells and/or their precursors. NK activities of LNL were augmented by IL-2 and OK-432, suggesting usefulness for local immune therapy.

Breast Neoplasms↗

Dexamethasone fails to produce antipyretic and analgesic actions in experimental animals.

In order to explore the role of phospholipase A2 inhibition in the mechanisms of the action of glucocorticoids, it was investigated whether the steroid exhibits the analgesic and antipyretic actions as well as cyclo-oxygenase inhibitors such as indomethacin or not. Dexamethasone has been reported to produce the anti-inflammatory action with a lag time of at least 1 h at doses of up to 0.1 mg/kg in mice and rats. However, dexamethasone when given 4 h beforehand had no significant analgesic activity even at doses of 1 and 10 mg/kg i.v. in the acetic acid writhing test in rats. In mice, the significant reduction in writhes counts was seen when dexamethasone (1 and 10 mg/kg i.v.) was given 15 min or 4 h before phenylquinone injection; i.e. the activity had not the lag time. On the other hand, dexamethasone showed a strong antipyretic activity against both the fevers caused by LPS and yeast in rats. In the yeast-febrile rats, the antipyretic activity had a lag time of about 1 h, and was dose-related at doses as low as 0.03 to 0.3 mg/kg i.v.; the steroid markedly reduced the increased PGE2 content in the cerebrospinal fluid. The antipyretic activity after local injection into the cerebroventricle or the yeast pouch was stronger than that after systemic injection into the tail vein, although so large a difference in the activity between the dosage routes was not seen, suggesting that the site of the antipyretic action is in both the brain and periphery. The antipyretic activity of dexamethasone (10 mg/kg i.v.) was not seen in rabbits with fever caused by LPS.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

Inhibition of prostaglandin generation in the rabbit brain in-vivo by AD-1590, a non-steroidal anti-inflammatory agent with potent antipyretic activity.

The inhibition of prostaglandin generation by AD-1590 was investigated in the rabbit brain in-vivo. AD-1590 (0.4 mg kg-1 i.v.) markedly prevented both the increases in body temperature and PGE2 level in cerebrospinal fluid (CSF) caused by i.v. injection of lipopolysaccharide. On the other hand, 2,4-dinitrophenol (20 mg kg-1 i.v.)-induced hyperthermia, which was not affected by AD-1590, was not accompanied by an increase in PGE2 level in CSF. When injected intracerebroventricularly, AD-1590 dose-dependently inhibited the hyperthermia caused by arachidonic acid given by the same route; its ED50 was 1.6 micrograms compared with about 35 micrograms for indomethacin. From these results, it is suggested that AD-1590 is more active than indomethacin in suppressing prostaglandin synthetase in rabbit brain.

Animals↗

[The role of the spleen in immunosuppression and the effects of splenectomy on prognosis in gastric cancer patients].

To elucidate the role of the spleen on the immunosuppression in gastric cancer patients, mechanism of the induction of suppressor cells in the spleen was investigated. Studies of tissue distribution of T cells using monoclonal antibodies revealed that spleen contained much higher proportion of OKT8 reactive T cells as compared with those in regional lymphnodes without metastasis. Lymphocytes released from the spleen during perfusion were taken to be representative of recirculating lymphocytes. Suppressor precursor cells were found to exist predominantly in perfusate from the spleen, while spontaneously activated suppressor cells were in the residual lymphocytes in the spleen after perfusion. Culture supernatants from splenic adherent cells induced suppressor cell activities as well as sera from splenic venous blood. These results suggest that suppressor precursor cells which could be mobilized slowly was more comparable to splenic lymphocytes and might be matured by factors released from splenic adherent cells, partly moving into peripheral blood. Furthermore, the effect of splenectomy on the prognosis of gastric cancer patients was investigated in randomized controlled trial. The patients who underwent total gastrectomy and had main location of the tumor on lesser curvature region were divided into two groups at random; splenectomy (+) and splenectomy (-) groups. A suggestive prolongation of survival time was observed in splenectomy (+) group. Thus, spleen seem to contribute to the immunosuppression in gastric cancer patients and splenectomy may lead to better prognosis.

Adult↗

Reaction of nucleic acids bases and their derivatives with peroxodisulfate ion.

Reaction with peroxodisulfate ion was investigated, that is, reaction of 1,3-dimethyluracil, 1,3-dimethylthymine, and caffeine with carbon radicals formed from decarboxylation of carboxylic acids, oxidation of the methyl group at 5-position of thymines, and halogenation of nucleic acids bases and their derivatives with alkali halides.

Caffeine↗

Central versus peripheral sites of antipyretic action of a non-steroidal anti-inflammatory agent, AD-1590, in rabbits.

The site of antipyretic action of AD-1590 in the sequential process involved in the development of fever caused by bacterial pyrogen (LPS) was investigated in rabbits. AD-1590 (1 microgram/ml) did not inactivate both LPS and leucocytic pyrogen (LP) and did not affect the generation of LP in the in vitro test. AD-1590 (0.1 mg/kg i.v.) prevented the fever caused by LP as well as LPS, but did not prevent the fever by PGE2 (100 ng/rabbit) injected into the preoptic anterior hypothalamic (PO/AH) regions. A significant antipyretic effect of AD-1590 on LPS-fever was found when AD-1590 (4 micrograms/rabbit) was injected into the PO/AH regions. AD-1590 (0.4 mg/kg i.v.) did not produce anti-pyretic activity against 2,4-dinitrophenol-hyperthermia; the monoamine levels in the brain were not affected with AD-1590 (10 mg/kg p.o.). These results suggest that AD-1590, like acidic non-steroidal anti-inflammatory drugs, produces its antipyretic action through the central mechanisms.

Animals↗

The enhancement of tumor cell susceptibility to macrophage binding and cytolysis by p-aminobenzoic acid-N-xyloside sodium salt (K-247).

The enhancement of tumor cell susceptibility to macrophage binding and cytolysis by the pretreatment of tumor cells by p-aminobenzoic acid-N-xyloside sodium salt (K-247) was investigated in the C3H/He mouse-syngeneic tumor system. Binding and cytolytic activities of Corynebacterium parvum-activated macrophages were significantly enhanced when target MM-102 and MH-134 cells were pretreated with K-247 at doses of 200 or 400 micrograms/ml, while thioglycollate-elicited macrophages showed much lower binding and lytic activities against K-247 pretreated target cells. No enhancement of these activities were observed when target cells were pretreated with D-xylose, which had no anti-tumor activity. Furthermore, in a binding assay a significant reduction of macrophage binding to target cells by the K-247 pretreated cold competitors was observed. It is suggested that target cell susceptibility to macrophage cytolytic activity might be enhanced by pretreatment with K-247, involving an initially increased target binding.

4-Aminobenzoic Acid↗

AD-1590, a potent antagonist of lipopolysaccharide-induced fever in rabbits.

The antipyretic activity of AD-1590 (2-[8-methyl-10,11-0xodibenz[b,f]oxepin-2-yl]propionic acid), a non-steroidal anti-inflammatory drug with a novel chemical structure, was investigated in rabbits with lipopolysaccharide (LPS)-induced fever and monkeys with leucocytic pyrogen-induced fever. AD-1590 produced a dose-related inhibition of the LPS-fever at oral doses of 0.1 mg kg-1 or more (ED50 = 0.089 mgg kg-1). Its potency was 10-12, 20-35, 100-170, 400-540, greater than 1500 and greater than 2000 times that of ketoprofen, diclofenac sodium, indomethacin, ibuprofen, mefenamic acid and aspirin, respectively. The fever caused by leucocytic pyrogen was significantly inhibited by intravenous administration of 0.1-0.2 mg kg-1 of AD-1590 (10 mg kg-1 oral or i.v.) did not affect body temperature in afebrile rabbits or monkeys. These results suggest that AD-1590 shows a potent antipyretic activity in the rabbit and monkey and is a potent antagonist of LPS-fever.

Animals↗

[Significance of human Tr cell in gastric cancer --with special reference to suppressor cell activity].

Peripheral blood lymphocytes from gastric cancer patients and normal donors were divided into T, non T, Tr, and T non-r cell fractions. Suppressor cell activity of each fraction and surface antigen of T cell subsets were investigated. T and Tr cell fractions activated by concanavalin A (Con A) significantly depressed the lymphocyte proliferative responsiveness (LP) to phytohemagglutinin (PHA) of responder autologous lymphocytes, but non T and T non-r cell fractions didn't. LP response to PHA of responder autologous cells were depressed by Tr cell fraction from gastric cancer patients without Con A activation, but not from normal donors. The percentage of Tr cells in T cells increased from 8.9% to 18.2% in gastric cancer patients, and from 4.7% to 9.5% in normal donors when lymphocytes were activated by Con A for 24 hours. The percentages of Tr cells reacting with OKT3, 4, and 8 monoclonal antibodies were 72.5%, 29.0% and 43.4%, respectively. Therefore, Tr cell was relatively enriched by OKT8 cell. The percentage of Tr cells and suppressor cell activity increased when normal lymphocytes were incubated with sera from gastric cancer patients for 24 hours and suppression by T, Tr and T non-r cell fractions 23%, 8% and 5%, respectively. From these results it is suggested that Tr cells contain suppressor precursors which can be activated by Con A in vitro and matured suppressor cells which have been already activated in vivo, and that higher proportion of suppressor precursors is found in gastric cancer patients as compared with normal donors. Furthermore, it is indicated that cancer sera may contain factors which induce suppressor cell and induction of suppressor cell activity requires the interaction between Tr cell and T non-r cell.

Antigens, Surface↗

[Local immunotherapy for cancer].

As for the non-specific cancer immunotherapy concerned, the effect is limited and local use of immunopotentiators which could collect effector cells around tumor tissues might be the best way of cancer immunotherapy. Intratumoral or intraperitoneal administration of large-dose of OK-432 (100 KE) has been investigated since many years with favorable results. Side effects were minimum with a few days continuing slight fever elevation. From the immunohistological examinations using monoclonal antibodies, participation of killer T cells and NK cells was confirmed after intratumoral administration of large-dose OK-432. On the other hand, after intraperitoneal administration of OK-432, neutrophil leucocytes appeared at first on the 2nd to 4th day and they were followed by lymphocytes on the 4th to 5th day and finally appeared lot of macrophages on the 6th and later days. From the results of in vitro and in vivo experiments, these macrophages seemed to play the leading role in the cytostatic activities after intraperitoneal OK-432 administration. As for the fear of introducing suppressor cells after large-dose OK-432 administration, detailed studies on suppressor activities before and after operation for gastric cancer patients revealed no particular increase of suppressor cell activities after intratumoral and intraperitoneal administration of 100 KE OK-432 as compared with curative resection cases with no OK-432 administration.

Adjuvants, Immunologic↗

Purification and properties of a cytochrome P-450 of a fungus, Fusarium oxysporum.

A cytochrome P-450 was isolated from a fungus, Fusarium oxysporum, which grew on a medium containing soybean oil as a sole carbon source. It was found as a heme protein that possess lipoxygenase activity, and seemed to exist in the soluble fraction of cell-free extracts. The cytochrome revealed multiplicity and could be separated into a least 3 fractions (A, B, and C). Two of them, termed Fusarium P-450A and -B, were highly purified. The complex of the ferrous Fusarium P-450 with carbon monoxide showed a Soret peak at 447 nm. The properties of the cytochromes (P-450A and -b) were closely similar to each other, the only detectable difference being in the pI (isoelectric point) value (5.2 and 5.0, respectively). The pI and molecular weight (48,000) values together with amino acid composition of Fusarium P-450 were similar to those of other cytochromes P-450 from various sources. Some other spectral properties as well as interactions with various ligands were also studied. Peroxidase or chloroperoxidase activity was not detected with Fusarium P-450.

Amino Acids↗

[Enhancement of antitumor activity of Propionibacterium avidum in combined with neurotropin in tumor bearing mice].

The enhancement of antitumor activity of Propionibacterium avidum (P. avidum) in combination with Neurotropin (NSP) was investigated in C3H mice-MH 134 tumor system. P. avidum (0.5 mg) and NSP (20 mg/kg) were administered on day 2 and from day 1 to 7 after tumor inoculation, respectively. When mice were treated with P. avidum in combination with NSP, a significant prolongation in survival days was observed (P less than 0.01). Treatment with P. avidum alone produced prolongation in survival days, but NSP did fail. Increase of Con-A induced suppressor cell activity and depressed proliferative response of spleen cells were observed by the treatment with P. avidum. However, recovery of proliferative response to normal level and disappearance of suppressor cell activity were observed when NSP was combined. Thus, treatment by P. avidum in combination with NSP produced a significant prolongation in survival days and it may be depending on macrophage activation by P. avidum and on the restoration of T cell functions by NSP.

Animals↗