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Biomedical subjects

S Tsuru

Publications and source records attributed to S Tsuru.

At least 109 records · Page 6Linked to original sources

Induction of impaired activation of lymphocytes by suppressive factor in Crohn's disease patients.

Lymphocyte proliferative response to phytohemagglutinin (PHA) and relevance of serum factors to the response were studied in 12 patients with Crohn's disease (CD). The lymphocyte proliferative response was markedly reduced in patients with Crohn's disease (S.I. = 38.8 +/- 36.8) (mean +/- SD), as compared with normal controls (S.I. = 100.6 +/- 28.6) (p less than 0.01). In addition, the effect of sera from patients with CD or 10 patients with ulcerative colitis (UC) who had extremely impaired lymphocyte responsiveness to PHA on the proliferative response of normal lymphocytes to PHA was also measured. Sera from CD patients had a marked suppressive effect on the blastogenesis of normal lymphocytes (S.I. = 46.4 +/- 28.5), as compared with normal sera (S.I. = 126.2 +/- 14.7) (p less than 0.001). On the other hand, UC sera did not suppress the blastogenesis of normal lymphocytes (S.I. = 114.9 +/- 27.7). Moreover, serum immunosuppressive acidic protein (IAP) levels in patients' sera were measured by single radial immunodiffusion assay. A marked increase in serum IAP levels was revealed both in CD patients (780 +/- 470 micrograms/ml) and in UC patients (601 +/- 278 micrograms/ml), as compared with normal controls (376 +/- 92 micrograms/ml) (p less than 0.001). But there was no precise correlation between the suppressive effect of sera and serum IAP levels in patients with CD. Thus, we demonstrated an impairment of the lymphocyte responsiveness to PHA in CD patients and the possible existence of immunosuppressive factors which is not identical with IAP in the sera from patients with CD.

Adult↗

Mechanism of protection during the early phase of a generalized viral infection. I. Contribution of phagocytes to protection against ectromelia virus.

Effects of carrageenan and gamma-irradiation on virus titre in the liver were observed after intravenous inoculation of 8 X 10(3) p.f.u. of ectromelia virus which was not lethal for untreated mice. Trapping of virus by the liver within 30 min and an initial transient reduction in titre by day 1 were not affected by gamma-irradiation but were inhibited by pretreatment with carrageenan. An increase from day 1 to day 3 was not affected by gamma-irradiation but was augmented by pretreatment with carrageenan. Therefore, protection within 3 days may depend principally upon carrageenan-sensitive and irradiation-resistant cells, namely, fixed macrophages. Elimination of virus from day 4 to day 7 depended upon cell-mediated immunity. When carrageenan was given 3 days after virus inoculation, the titre of virus increased progressively from day 4 ultimately to kill the hosts. The cytotoxic activity of spleen cells against infected target cells was raised in carrageenan-treated mice as well as in untreated mice. Immune elimination of virus may be mediated by a mechanism requiring the cooperation of sensitized T lymphocytes and blood monocytes.

Animals↗

Regulation of lymphocyte responses in cancer patients. I. Study of cell-surface gangliosides by cholera toxin and their induction of impaired activation.

The gangliosides compose a major portion of the surface membrane structure of the lymphocytes and their expression may relate with functional properties of different lymphocyte subpopulations. In the present study, the binding of the ganglioside GM1 to the human peripheral blood mononuclear cells (PBMC) and their effects on the lymphocyte function were examined. Cholera toxin (CT) was used as an indicator for detection of GM1 on the cell surface. It was shown that the exogenous GM1 binds to normal PBMC and inhibits proliferative responses in vitro by various mitogens (Con A, PHA, PWM). It was also revealed that more than 18 h is required to induce unresponsiveness of lymphocytes by preincubation with GM1, even though GM1 bound very rapidly (10-30 min) to lymphocytes. Some intracellular event may be needed to induce unresponsive state of the lymphocytes by GM1 binding. Moreover, the number of CT binding lymphocytes and the amount of CT bound to each cell showed to increase in the cancer patients. These results suggest that the increase of GM1 in the serum and the lymphocyte surface may be one of the mechanisms of suppressed lymphocyte responsiveness in the various pathological states especially in the cancer patients.

G(M1) Ganglioside↗

Circulating antibodies to the surface antigens on colon epithelial cells in ulcerative colitis.

The fluorescence activated cell sorter (FACS) was used for detecting circulating antibodies to the surface antigens on isolated colon epithelial cells (anti-colon antibodies) by indirect immunofluorescence. Anti-colon antibodies were found in the serum of 30 of 41 (73%) patients with ulcerative colitis. This incidence is much higher than one established in earlier reports by application of indirect immunofluorescence to colon tissue using the fluorescence microscope. The results suggest that FACS analysis is very useful for detecting antibodies to colon specific antigen.

Adult↗

Effects of PSK on specific tumor immunity to syngeneic tumor cells.

Substantial degrees of resistance against rechallenge with viable tumor cells and cytotoxic activity of peritoneal exudate cells (PE cells) as detected by in vitro 51Cr-release test or in vivo Winn's test were raised by immunization with Mitomycin C-treated EL-4 tumor cells in syngeneic C57BL/6J mice. Cytotoxicity of PE cells was found to reside in glass-nonadherent and anti-Thy 1.2-sensitive population, while such activity was not detected within the spleen and mesenteric lymph nodes. Intraperitoneal or oral administration of PSK augmented such resistance or cytotoxicity.

Animals↗

[Effect of solcoseryl and combined therapy of solcoseryl and FT-207 for mice bearing meth-A tumor].

The effects of a combined chemotherapy of solcoseryl and FT-207 on tumor growth, delayed hypersensitivity and cell population of the spleen were studied using inbred BALB/c mice. Meth-A tumor cells (2 X 10(6] were inoculated into the back of 5 to 6 week old BALB/c male mouse. Animals were divided into three groups: Solcoseryl group, in which 0.04 mg of solcoseryl was injected intravenously three times before inoculation and four times after inoculation; Combined group, in which 1.2 mg of FT-207 and 0.04 mg of solcoseryl were injected intravenously four times after inoculation; FT-207 group, in which 1.2 mg of FT-207 was injected four times after inoculation, with out solcoseryl administration. Following results were obtained: Solcoseryl group showed enhanced immunity and tumor suppression; Decreased immunity due to FT-207 was recovered by administration of solcoseryl but no tumor suppression was observed and, Decreased T-cell population of spleen due to FT-207 was recovered by administration of solcoseryl. These facts suggested that solcoseryl was useful because of making recovery possible from decreased immunity due to chemotherapy.

Actihaemyl↗

Effects of cholera toxin on the lymphoid system. III. In vivo generation of cytotoxic lymphocytes.

Cytotoxic T lymphocytes (CTL) were generated in the spleen by subcutaneous inoculation of EL-4 leukaemia cells (H-2b) into C3H/He mice (H-2k). (1) Cytotoxicity of spleen cells was profoundly suppressed by an intravenous injection of 1 microgram cholera toxin on the day of tumor inoculation. Tumors continued to grow progressively. (2) Differentiation of memory cells to mature CTL was suppressed by cholera toxin injection on the day of booster inoculation of EL-4 cells. The tumors grew progressively in immune mice given cholera toxin on the day of the booster. (3) In vitro treatment of CTL with cholera toxin suppressed the expression of their cytotoxic activity to a considerable extent. However, tumors regressed very rapidly after rechallenge to immune mice carrying CTL, even when cholera toxin was injected on the day of rechallenge. Cholera toxin suppressed not only the functional expression of CTL but also the induction phase of CTL generation.

Animals↗

Augmented delayed footpad reaction in thymus cell-depleted mice induced by cholera toxoid.

One hundred microgram of cholera toxoid was injected intravenously into DDD and AKR mice and its effects on lymphoid tissues and immune responses against sheep erythrocytes (SRBC) were examined at various times after the injection. (1) A remarkable reduction of thymus cells was revealed from day 1 to 7 and from day 1 to 4 in DDD and AKR mice, respectively. (2) Cholera toxoid exhibited only slight effects on the numbers of spleen cells and peripheral blood leukocytes in both strains. (3) Delayed footpad reactions to SRBC were augmented by a pretreatment with cholera toxoid 4 or 7 days before immunization in both strains. The delayed reactions were not suppressed in the presence of a prominent antibody production and were accompanied by positive macrophage migration inhibition. (4) Antibody production against SRBC, especially of IgG class, was facilitated, when cholera toxoid was given 7 days before the immunization through the footpad in DDD mice. On the other hand, antibody production was suppressed irrespective of immunizing routes and mouse strains, when cholera toxoid was given 1 day before immunization.

Animals↗

Involution of the thymus in tumor-bearing mice and its restoration by PSK.

In Balb/C mice, the size and weight of the thymus and the number of thymus cells were reduced 1 week after the subcutaneous inoculation of Meth A fibrosarcoma. These changes were prevented by the intraperitoneal administration of PSK. In normal mice, the majority of thymus cells are large and the minority are small as demonstrated by analysis with a fluorescence activated cell sorter. In tumor-bearing mice, the number of large cells are decreased and the number of small cells are relatively increased. PSK prevented such a modulation in tumor-bearing mice.

Animals↗

Entrance of cholera enterotoxin subunits into cells.

Quantitative analysis of the staining of cholera enterotoxin on the surface of cells with specific antibodies against each subunit of cholera toxin, using a Fluorescence-Activated Cell Sorter, showed that not only subunit A but also subunit B penetrates the cell membrane. The detection of each subunit inside the cell was facilitated by the use of saponin, an agent which increases membrane permeability.

Animals↗

Production by cultured spleen cells of inflammatory substances and other lymphokines that mediate delayed-type hypersensitivity in mice.

In vitro cultivation of normal mouse spleen cells with human serum albumin generated effector cells that mediate the delayed-type hypersensitivity (DTH) reaction. The cultured cells, when incubated in a serum-free medium for a further 24 hr, released substances (FPRF) which caused a footpad inflammatory reaction at a maximum of 6 hr after injection into normal syngeneic or allogeneic strains of mice, as well as macrophage migration inhibition factor (MIF) and macrophage activating factor (MAF). The DTH-effector cells in the culture were fractionated in the low density layers by discontinuous bovine serum albumin density gradient centrifugation. The effector cells in the low density layers were further enriched in the Lyt 1 subpopulation of T cells when fractionated on a fluorescence activated cell sorter. Cells capable of producing the inflammatory substances (FPRF), MIF and MAF were also enriched in the same fraction containing DTH-effector cells. These results suggest that low density, Lyt 1-positive T cells mediating the DTH reaction produce FPRF as well as MIF and MAF.

Animals↗

Experimental study on immunological reactions against the articular cartilage.

In rats immunized with articular cartilage antigens, delayed hypersensitivity was detected by the macrophage migration inhibition test and delayed footpad reaction. Additionally, a proliferative response was found in the regional lymph nodes of immunized rats. The mixed addition of sensitized lymphocytes and antibodies exerted a cytotoxic effect on cultured chondrocytes. Articular damage including accelerated chondrolysis may have some relation to delayed hypersensitivity to autologous articular cartilage antigens.

Animals↗

[Effect of PSK on tumor-specific immunity induced by MMC-treated syngeneic tumor cells].

Immunization with MMC-treated EL-4 tumor cells could raise cytotoxic activity of non-adherent PE cells and resistance against rechallenge with small or medium doses of viable tumor cells. Administration of PSK augmented the generation of cytotoxic lymphocytes and the induction of resistance against rechallenge in mice immunized with such MMC-treated tumor cells. Augmented generation of cytotoxic lymphocytes may be ascribed to systemic effects of PSK but not to local effects in the peritoneal cavity, since augmenting effects of PSK were observed not only after intraperitoneal administration but also after oral administration. Either after intraperitoneal administration or after oral administration cytotoxic activity was detected in PE cells but not in spleen cells. Cytotoxic activity was detected in PE cells but not in spleen cells after intraperitoneal injections of MMC-treated tumor cells. Cytotoxic lymphocytes appear to differentiate to their mature form capable of being detected by 51Cr-release test principally at the site of direct graft rejection. Intraperitoneal administration of PSK was more effective in the augmentation of cytotoxicity of PE cells than oral administration. PSK may be able to have contact with precursors of cytotoxic lymphocytes more efficiently after intraperitoneal administration. Immunity against syngeneic tumor cells appears to be effective in elimination of small doses of tumor cells but to be overcome by medium or large doses of tumor cells at the rechallenge. Administration of PSK increased the threshold number to be eliminated by immune hosts. This finding seems to be important in relation to augmentation of resistance against metastasis or local implantation with a limited number of tumor cells.

Animals↗

Characterization of immunoregulatory T cells and lymphocytophilic antibodies in ulcerative colitis: analysis with monoclonal antibodies.

Using monoclonal antibodies to the surface antigens or suppressor/cytotoxic (Anti-Leu-2a) and helper/inducer (Anti-Leu-3a) T cell subsets, we characterized peripheral lymphocytes in 27 patients with ulcerative colitis (UC) and 15 age-matched healthy controls by a fluorescence activated cell sorter. The patients with active UC had a reduced percentage (8.2 +/- 3.6%) of Anti-Leu-2a reactive subset in comparison with healthy controls (24.6 +/- 3.6%) (P less than 0.01). No significant change was found in the percentage of Anti-Leu-3a reactive T cells between the patients and the controls. Moreover, the relationship of lymphocytophilic antibodies found in the patients with UC to the T cell subsets was also examined. After a fraction of normal T cells was eliminated with treatment of the sera from patients with active UC, the percentage of T cells reactive with Anti-Leu-2a decreased from 25 to 15%, whereas the percentage of T cells reactive with Anti-Leu-3a increased from 40 to 70%. In the reciprocal study, the lymphocytophilic antibodies reacted with 80% of Leu-3a negative T cells and 65% of Leu-2a negative T cells. These results demonstrated that the lymphocytophilic antibodies found in UC patients are reactive with suppressor T cells and thus play an important role in the loss of peripheral suppressor cells in the active UC patients. The lymphocytophilic antibodies were also demonstrated to be reactive with non-helper, non-suppressor T cell subsets and some populations of helper T cells. These studies suggest the presence of immune-regulatory disturbances contributing the pathogenesis of UC.

Adult↗

Anti-colon antibody and lymphocytophilic antibody in ulcerative colitis.

The presence of anti-colon antibody in the sera from patients with ulcerative colitis was demonstrated by antibody-dependent cell-mediated cytotoxicity (ADCC) assay. In addition, the high prevalence of lymphocytophilic antibody in the sera from patients with ulcerative colitis was obtained by fluorescence activated cell sorter (FACS) analysis. This lymphocytophilic antibody was absorbed by rat colon epithelial cells. Moreover the lymphocytes from ulcerative colitis showed lower binding capacity to this antibody, but acquired higher binding capacity after 20 hr incubation at 37 degrees C in vitro. These data suggest that ADCC may have some role in the pathogenesis of ulcerative colitis.

Antibodies↗