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Biomedical subjects

S Tsuru

Publications and source records attributed to S Tsuru.

121 records · Page 7Linked to original sources

Decrease in cholera toxin-binding T cells in aged mice and human volunteers.

The capacity of T cell-enriched populations of cells from mice and human volunteers to bind cholera toxin was analyzed by means of a fluorescence-activated cell sorter. In aged mice and humans, the number of cells capable of binding high concentrations of cholera toxin was lower than that in young mice and humans. The capacity to bind cholera toxin may be one of the useful indicators for the detection of aging in the immune system.

Adult↗

Effects of cholera toxin on lymphoid system. I. Reduction of thymus cells after cholera toxin injection.

One microgram of cholera toxin was injected intravenously into DDD and AKR mice and its effects on lymphoid tissues were examined at various intervals. A remarkable reduction of thymus cells were revealed from days 1 to 11 and from days 1 to 7 in DDD and AKR mice, respectively. Only slight effects were detected on the numbers of spleen cells and peripheral blood leukocytes in both strains throughout the observation period.

Animals↗

Effects of cholera toxin on the lymphoid system II. Selective augmentation of delayed footpad reaction in mice.

Effects on immune responses to sheep erythrocytes (SRBC) were examined at various intervals after an intravenous injection of 1 microgram of cholera toxin in DDD and AKR mice. Delayed footpad reaction was augmented by pretreatment with cholera toxin 1, 7 or 10 days before immunization in both strains. The delayed reaction was not suppressed even in the presence of a prominent antibody production. In mice given cholera toxin, macrophage migration inhibition was not positive 5 days after immunization, but became weakly positive 10 days after immunization. Antibody production against SRBC especially of IgG class, was facilitated, when cholera toxin was given one day before immunization, on the other hand, antibody production was suppressed irrespective of immunizing routes and mouse strains. Similar results were observed in guinea pigs which were injected with 1 microgram of cholera toxin 0 or 7 days before immunization with bovine gamma globulin in complete or incomplete Freund's adjuvant. Erythema was augmented strikingly by cholera toxin, while macrophage migration inhibition was affected scarcely.

Animals↗

Cyclic AMP and immune responses: identification of prostaglandin E-producing cells in mouse spleens.

Previous work has shown that normal mice respond to the intravenous injection of sheep erythrocytes (SRBC) with a transient increase in splenic cyclic AMP peaking after 2 minutes, and this cyclic AMP response has been shown to be due to prostaglandins (PGs) released from antigen-specific cells. In the present study, the cell type responsible for PG production in response to antigen was determined using a fluorescence-activated cell sorter (FACS) and an electron microscope. C57Bl/6 mice injected with SRBC showed a 2% increase of PGE-producing spleen cells relative to controls. In control mice injected with phosphate-buffered saline (PBS), 19% of the spleen cells produced PGE. An electron microscopic study of PGE-producing cells sorted on FACS showed that they were small lymphocytes and plasma cells. In addition, nude mice also increased the number of PGE-producing spleen cells in response to antigen. These findings suggest that lymphocytes involving at least B-cells respond to antigen with an increase in PGE production.

Animals↗

Effect of cyclic cisplatin and etoposide therapy with continuous UFT administration on the recurrence of endometrial cancer in nude mice.

Effects of cisplatin and etoposide chemotherapy and/or continuous administration of oral anticancer agent UFT following the initial chemotherapy with cisplatin and etoposide on the tumor recurrence rate were studied in endometrial cancer-bearing mice. Complete response (CR) rate of cyclic administration of cisplatin and etoposide (91%) was significantly higher than that in the control group (60%; p < 0.05). Continuous UFT administration raised a CR rate of 75%, which was not significantly higher than that of the control group. When cyclic administration of cisplatin and etoposide was combined with continuous UFT administration, 100% of CR rate was obtained (p < 0.01). Our results suggest that cisplatin-based cyclic chemotherapy has a therapeutic effect on gynecologic malignancies and is particularly effective in preventing tumor recurrence in mice. Combining this therapy with continuous administration of an oral anticancer agent enhances its therapeutic effect.

Administration, Oral↗

Thymidylate synthase activity as a prognostic factor in ovarian cancer.

We assayed thymidylate synthase (TS) activity and performed flow-cytometric DNA analyses in fresh tumor tissues from 38 patients with ovarian cancer. TS activity was closely correlated with prognosis but was not related to age, clinical stage, histologic type or lymph node metastases. Patients with TS activity higher than 2.0 pmol/g tissue had significantly worse prognoses than those with lower levels (p < 0.01). Also, patients with DNA aneuploidy or high S-phase fractions (> 20%) had worse prognoses than those with DNA diploidy or lower fractions. Results suggest that TS activity may be a good prognostic indicator in ovarian cancer.

Adult↗

Effects of cisplatin on cell cycle kinetics, morphological change, and cleavage pattern of DNA in two human ovarian carcinoma cell lines.

We evaluated the effects of cisplatin on the cell kinetics, cytomorphological changes, and cleavage patterns of DNA in two lines of human ovarian carcinoma cells. KF-1 cells displayed a cell cycle arrest in the G2M phase, while HMG cells displayed a transient cell accumulation in the S phase, without obvious G2M arrest. Morphological changes characterized by condensation and fragmentation of chromatin, and DNA cleavage by oligonucleosome-sized DNA fragments were observed in the HMG cells but not in the KF-1 cells. The pattern of cell death in HMG cells was considered to be apoptosis, but that of KF-1 cells necrosis. These findings showed the different mechanisms of anti-tumor effect of cisplatin on human ovarian carcinoma cell lines, including cell kinetics and pattern of cell death.

Carcinoma↗

Functional changes of alveolar macrophages in carragheenan-induced aspiration pneumonia model mice.

Alveolar macrophages (AMs) are cells with unique characteristics because of their localization in the aerobic environment and are receiving stimuli by inhalation. To estimate the functional changes of AMs induced by inflammation, a murine model of aspiration pneumonia was made by an intratracheal injection with carragheenan, whose mortality rate was approximately 25%. The cell component which increased predominantly in the inflammatory site was polymorphonuclear leukocytes, and the number of AMs did not show a remarkable increment. Control group showed a high level of intracellular oxidation of 2'7'-dichlorofluorescin (DCFH) by AMs, while that in carragheenan-treated mice decreased significantly (p < 0.05). There were two populations in AMs classified according to the oxidative activity of DCFH; the population showing high oxidative activity of DCFH was asialo GM1 positive, in contrast, that with lower oxidative activity was asialo GM1 negative. Decrease in DCFH-oxidative activity of AMs in control group was observed after a treatment with KCN or deferoxamine. But in the carragheenan-treated group, this decrease was not observed after treatment with KCN. These results show that both oxygen-derived radical produced in mitochondria, which is inhibited by KCN, and cytoplasmic OH radical, which is selectively inhibited by deferoxamine, are concerned with intracellular oxidation of DCFH by AMs, and that a decrease in DCFH-oxidative activity in the carragheenan-treated group was attributed to the depression of mitochondrial respiration. Nevertheless, increased expressions of Ia and F4/80 in AMs of the carragheenan-treated group were observed and phagocytic activity was well preserved at the control level. These results suggest that AMs may play a crucial role, as well as differentiated phagocytes possessing antigen-presenting ability and/or digestive activity against various types of foreign bodies despite showing an obvious decrement in oxidative activity. These results imply that AMs have a strong oxidative activity and deal with various types of antigens in normal states, but in case of acute inflammation they will change into mature type macrophages with high expression of class II molecules which correlates with an antigen-presenting capacity.

Amino Acid Oxidoreductases↗

Effects of macrophage colony-stimulating factor on the activities of murine monocytes and peritoneal macrophages in vivo.

The ability of peripheral blood monocytes, granulocytes and resident peritoneal macrophages to generate hydrogen peroxide in response to concanavalin A was enhanced by a single intravenous injection of macrophage colony-stimulating factor (M-CSF) of recombinant human type in AKR mice. In response to phorbol myristate acetate, only granulocytes and resident peritoneal macrophages showed the enhanced ability. Phagocytosis by those cells was not stimulated by M-CSF. Surface marker analysis showed an increased expression of F4/80 and Mac1 on monocytes, Mac1 expression on granulocytes and LFA-1 expression on resident peritoneal macrophages. Ia antigen on resident peritoneal macrophages was suppressed by M-CSF. M-CSF can induce monocytes, granulocytes and resident peritoneal macrophages to generate hydrogen peroxide and enhances their maturation in vivo.

Animals↗