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Biomedical subjects

S Tsuru

Publications and source records attributed to S Tsuru.

At least 73 records · Page 4Linked to original sources
PubMed1988

[Effects of UFT on experimental liver metastases and on the immunologic capacity of the hosts].

An experimental model is introduced for the study on liver metastasis using intrasplenically injected EL-4 and Lewis lung tumor (LLT) cells. The inhibitory effects of UFT, FT and 5-FU on the frequencies of metastatic foci in the liver were compared. All drugs showed inhibitory effect on the frequencies of liver metastasis. However, a high dose of UFT suppressed strongly the frequencies of liver metastasis. In order to compare the immunosuppressive activity of UFT with that of FT and 5-FU at the dose to give 50% inhibition of liver metastasis (MED50), we determined the MED50 values of UFT, FT or 5-FU against liver metastasis of EL-4 and LLT cells. FT and 5-FU were suppressed strongly the humoral response against SRBC, the delayed hypersensitivity against picryl chloride and the phagocytic activity. UFT had no inhibitory effect on immune responses.

Administration, Oral↗
PubMed1988

Inhibition of tumor growth by dairy products.

Effects of dairy products (cheeses and yoghurt) on growth of transplanted murine tumors were examined in various tumor-host combinations. Suppression of tumor growth was observed in proportion to the duration of feeding. Peripheral lymph-node (LN) cells of mice fed dairy products showed an increment in the fluorescence intensity of Thy-1.2+ cells in FACS analysis. These cells showed an augmented PHA response and a remarkable antitumor effect in tumor neutralization test (Winn's assay) compared to control lymphocytes. These results suggest that dairy products enhance the activity of peripheral LN cells to suppress the tumor growth. Moreover, serum transfer from cheese fed mice revealed the protective effects against tumors, while that from yoghurt fed mice did not show such an effect. In the former mice, serum iron level was increased compared to control levels but antibody response to sheep erythrocytes (SRBC) was not augmented. From these results, we propose a hypothesis that lymphocytes may be activated by transferable serum factors such as iron-saturated transferrin and suppression of tumor growth caused by the effector-target interaction which is mediated by effector-associated transferrin in the case of cheese fed mice. In yoghurt fed mice another mechanism is suspected because of the low level of serum iron.

Animals↗
PubMed1988

Effect of a high-fat diet on resistance to Listeria monocytogenes.

Effects of a high-fat diet on macrophage (M phi) functions were investigated. Eight-week-old ddN mice were fed a high-fat diet and carbon clearance was tested. Remarkable suppression of phagocytic activity (K16) was observed in mice fed such a diet for 1 or 2 weeks. Resistance against Listeria monocytogenes inoculated intravenously (iv) with a lethal, a sublethal, or a non-pathogenic dose was observed in the liver of mice fed a high-fat diet. When mice were infected with a lethal dose of bacteria, the number of listeria increased progressively in the liver to kill both control and a high-fat diet fed mice by day 4. The number of listeria revealed no significant difference between the group in the case of low dose inoculation. High-fat diet fed mice given a sublethal dose of bacteria showed a rise in the number of viable bacteria during the first 3 days after infection while a decline in the number of bacteria was observed in control mice during such a period. Suppression of M phi activity induced by a high-fat diet may account for the reduced resistance.

Animals↗
PubMed1987

Mechanism of protection during the early phase of a generalized viral infection. II. Contribution of polymorphonuclear leukocytes to protection against intravenous infection with influenza virus.

The contribution of phagocytes to the early protection of mice inoculated intravenously with influenza virus was investigated in phagocyte-depleted mice. Following the inoculation of a sublethal dose of influenza virus, virus titres in the liver and lung of both untreated and carrageenan-treated mice were reduced rapidly by day 1 and decreased slowly to reach an undetectable level by day 7. The titres in gamma-irradiated mice decreased transiently by day 1 and increased progressively thereafter to kill all of the hosts by day 8. The clearance of virus from blood at the early stage of infection was retarded by gamma-irradiation but not by carrageenan treatment. In addition, increase in virus titres in the liver and lung in the early stage of the infection was prevented by adoptive transfer with syngeneic polymorphonuclear leukocytes into gamma-irradiated mice. No significant rise of neutralizing antibody was detectable by day 3 after the inoculation, in any of the three groups of mice. These observations imply that gamma-sensitive and carrageenan-resistant polymorphonuclear leukocytes play a protective role at the early stage in the infection, whereas fixed macrophages or natural killer cells, both of which are carrageenan-sensitive and gamma-resistant, scarcely participate in the early phase.

Animals↗
PubMed1987

Protective mechanisms against pulmonary infection with influenza virus. I. Relative contribution of polymorphonuclear leukocytes and of alveolar macrophages to protection during the early phase of intranasal infection.

The relative contribution of polymorphonuclear leukocytes and macrophages in the early protection against intranasal infection of mice with influenza virus was investigated. Virus multiplication in the lung in the early phase of infection with less than 1.5 X 10(3) plaque-forming units was enhanced by X-ray irradiation. The intranasal administration of carrageenan did not influence the titre of virus. However, when mice were infected with 1.5 X 10(4) plaque-forming units, the virus titre was elevated by intranasal administration of carrageenan as well as by X-ray irradiation, but not by intraperitoneal administration of carrageenan. The intranasal administration of carrageenan not only inhibited the phagocytic activity of alveolar macrophages but also enhanced susceptibility to the virus. On the other hand, polymorphonuclear leukocytes were capable of phagocytosing the virus in vitro and were non-permissive for virus infection. Neutralizing antibody and interferon were not detectable in the early stage of the infection. These results suggested that polymorphonuclear leukocytes (X-ray-sensitive, carrageenan-resistant) were the cells primarily responsible for early protection in influenza virus infection and that after infection with a high dose of the virus alveolar macrophages (X-ray-resistant, carrageenan-sensitive) also played a protective role in the early phase.

Administration, Intranasal↗
PubMed1987

Oral immunization in adult mice to live and heat-killed Vibrio cholerae.

Effects of systemic and intestinal local immune responses in mice fed ad libitum and forcedly with live or heat-killed Vibrio cholerae on the elimination of vibrios from the intestine were investigated. In mice fed with live vibrios, ad libitum feeding could induce potential delayed-type hypersensitivity and rapid production of vibriocidal antibody in the serum whereas forcedly feeding suppressed the delayed-type hypersensitivity and retarded the antibody production. In contrast, when killed microorganisms were used as antigens, significant delayed-type hypersensitivity and rapid response of vibriocidal antibody were induced in forcedly fed mice although ad libitum feeding suppressed the induction of the delayed-type hypersensitivity and retarded the production of vibriocidal antibody. The elimination of vibrios from the intestine of mice was promoted in both mice groups fed ad libitum and forcedly with live vibrios but not with killed microorganisms. Total IgA in the intestinal contents of mice fed with live vibrios both ad libitum and forcedly were higher than those of mice fed with killed antigens. In addition, when the extracts of intestinal contents were absorbed by live antigens, IgA contents in mice fed with live vibrios were reduced more markedly than those in mice immunized orally by the feeding with killed antigens. These findings suggested that the elimination of vibrios from the organ was closely related to local IgA antibody response to heat-labile substance of live Vibrio cholerae.

Animals↗
PubMed1987

Cholera toxin-induced tolerance to allografts in mice.

When C3H/HeN (C3H) mice were primed with viable C57BL/6 (B6) spleen cells and treated with cholera toxin (CT) on the same day, a profound tolerance to tumour allografts of B6 origin was induced. The tolerant state was sustained for as long as 6 weeks or more. Skin allografts of B6 were rejected by such tolerant C3H mice, although the survival times were prolonged very slightly. Generation of cytotoxic T lymphocytes was reduced markedly in the tolerant mice, whereas delayed footpad reaction to B6 cells was maintained at the normal immune level or higher. There is a possibility that a T-cell subset responsible for delayed footpad reaction is resistant to CT-induced tolerance and participates in the rejection of skin allografts in tolerant mice.

Animals↗
PubMed1987

Contradictory responses in induction of delayed type hypersensitivity in orally immunized mice.

Induction of delayed type hypersensitivity (DTH) in mice fed with sheep red blood cells (SRBC) and live Vibrio cholerae (V. cholerae) both forcedly and ad lib was comparatively investigated. Although suppression of DTH to SRBC or V. cholerae was induced in mice fed forcedly for 1 or 2 weeks, mice fed ad lib could produce the positive footpad reactions to antigens. Furthermore, the suppression of DTH in forcedly fed mice showed an antigenic specificity. These observations indicated that the induction of unresponsiveness to DTH in orally immunized mice was markedly influenced by the oral administration.

Administration, Oral↗
PubMed1987

Enhancement of host defence by Y-19995 (2,4'-bis(1-methyl-2-dimethyl-aminoethoxyl)-3-benzoylpyridine dimaleate), a novel synthetic compound. I. Accelerated restoration from the leukocytopenia and augmented protection against microbial infections in immunocompromised mice.

Effects of a novel synthetic compound, Y-19995, on the host defence in immunocompromised mice were investigated in terms of the restoration of leukocytopenia and the protection against several microbial infections. Oral or intravenous administration of Y-19995 into mice after X-irradiation, treatment with cyclophosphamide or mitomycin C prevented the leukocytopenia to some extent and promoted the restoration in cell numbers of both the peripheral blood leukocytes and bone marrow. Intravenous administration of Y-19995 increased significantly the survival rates of X-ray irradiated mice against acute systemic infections with Escherichia coli, Pseudomonas aeruginosa and Candida albicans, and intramuscular infection with Escherichia coli. The clearance of Escherichia coli from the blood of X-ray irradiated mice was also promoted by the treatment with Y-19995. The augmented protection against microbial infections in immunocompromised hosts by Y-19995 may be attributed mainly to the prevention of leukocytopenia or the enhanced restoration from leukocytopenia.

Animals↗
PubMed1987

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

In C3H/He mice, the weight and cell number of the thymus were reduced and the size distribution (scatter profile measured by flow cytometer) of the thymus cells was changed 1 week after subcutaneous inoculation of X5563 plasmacytoma. This involution and change were prevented by intraperitoneal or oral administration of PSK. We examined the mechanism of this involution and change in thymus and the effect of PSK on them. In X5563-bearing C3H/He mice, 3H-thymidine incorporation into the thymus was reduced compared with that in control mice, as evaluated not only per organ but also per 1 mg of thymus tissue. Such reduction was inhibited by PSK. The substance (IS substance) which possessed a suppressive activity against mitogen induced lymphocyte proliferation, was partially purified from the ascites of X5563-bearing mice by the combination of ammonium sulfate precipitation and Sephacryl S-200 chromatography. IS substance was demonstrated to suppress the antibody response and delayed type foot-pad response against sheep red blood cells in mice. The reduction of weight and cell number and the change of scatter profile in thymus were caused by injection of this substance even in tumor-free mice. The restorative effects of PSK were observed also in IS substance injected mice. These results suggested that the various changes in the thymus observed in tumor-bearing mice might be attributable to the suppression of cell proliferation in the thymus, that such suppression was caused at least partly by an immunosuppressive substance which possessed inhibitory activity against lymphocyte proliferation, and that PSK had an antagonistic activity against such a substance so as to restore the function of the thymus in tumor-bearing hosts.

Animals↗
PubMed1987

Alteration of T cell maturation and proliferation in the mouse thymus induced by serum factors from patients with ulcerative colitis.

Recently it has been reported that patients with ulcerative colitis (UC) often have thymus abnormalities, although the precise mechanisms which induce those abnormalities remain unclear. We have examined the effect of serum fractions from patients with UC and other colonic diseases on mouse thymus to clarify the possible existence of factors which have thymus growth activity. These fractions were separated from sera of patients with UC by gel filtration and anion exchange high performance liquid chromatography. In mice given UC serum fractions; (i) remarkable increases in weight and total cell number of the thymus were observed from day 4 to day 9; (ii) a significant increase in the number of peanut agglutinin (PNA)+ thymus cells was demonstrated using flow cytometry on day 9; (iii) on quantitative analysis of surface antigens the percentage of Lyt-2+ thymus cells decreased and that of L3T4+ thymus cells increased remarkably on day 13; the number of bright Thy-1.2+ cells and of dull Lyt-1+ cells increased. In contrast, the serum fractions from patients with other colonic diseases and from normal persons caused little change in mouse thymus throughout the study. The results suggest that factors fractionated from the serum of patients with UC disturb intra-thymic T cell maturation and enhance the proliferation of thymus cells.

Animals↗
PubMed1987

Treatment of autoimmune MRL/Mp-lpr/lpr mice with cholera toxin.

The autoimmune manifestations of MRL/Mp-lpr/lpr(MRL/l), a murine model of systemic lupus erythematosus (SLE), were alleviated by administering 1 microgram cholera toxin (CT) every 14 days. The beneficial effects were: (i) significant prolongation of survival time, (ii) prevention of lymphadenopathy, (iii) improvement of T cell mitogenic responses and suppression of a B cell mitogenic response, (iv) decrease in serum anti-DNA and anti-Sm antibodies, (v) increase in IL-2 production by stimulation of spleen cells with concanavalin A (Con A). It is possible that CT may be effective for treatment of murine lupus nephritis by modulating polyclonal lymphocyte activation. This type of immunomodulation may pave the way toward treatment of lupus and other autoimmune diseases.

Animals↗
PubMed1987

Enhancement of host defence by Y-19995 (2,4'-bis(1-methyl-2-dimethyl-aminoethoxyl)-3-benzoylpyridine dimaleate), a novel synthetic compound. II. Activation of phagocytic cell functions.

A novel synthetic compound, Y-19995 potentiated phagocytic activity of rat or mouse peritoneal polymorphonuclear leukocytes in vitro or in vivo, respectively. The agent enhanced NBT reducing capacities of rat and guinea pig polymorphonuclear leukocytes in the peripheral blood ex vivo. Y-19995 restored from phagocytic activity of mouse peritoneal macrophages suppressed by the treatment with prednisolone ex vivo. In addition, IL-1 production by mouse macrophages was augmented by culturing with the agent in vitro. Furthermore, Y-19995 potentiated both phagocytic activity and NBT reducing capacity of human peripheral polymorphonuclear leukocytes in vitro. These results suggested that the activation of phagocytic cell functions by Y-19995 contributed to the enhancement of host defence in immunocompromised hosts.

Adjuvants, Immunologic↗
PubMed1987

Differing resistance to polymorphonuclear cells of halophilic- and hypotonic-types of Vibrio vulnificus.

Bacterial growth and lethality of 4 strains of Vibrio vulnificus infection of mice were enhanced by gamma-irradiation but not by treatment with carrageenan. Therefore, protection against V. vulnificus, at least in the early phases, probably depends mainly on polymorphonuclear cells (PMN), since carrageenan depletes macrophages but not PMN. PMN dependent protection against infection differs for 2 types of V. vulnificus strains. Halophilic- and hypotonic-type were distinguished from the corresponding parent strain. The hypotonic-type of the strains had capsular materials, as clarified by electron microscopic observation of the organisms stained with ruthenium red. On the other hand, halophilic-types either had no observable capsular materials, or incomplete materials, in contrast to the corresponding hypotonic-type. The corresponding halophilic- and hypotonic-types of the strains were compared for virulence in mice. The strains with capsular materials acquired resistance to phagocytic activity and were highly lethal. Capsular materials of V. vulnificus are no doubt important for the expression of virulence.

Animals↗
PubMed1986

Induction of interleukin 2 receptor gene expression by p40x encoded by human T-cell leukemia virus type 1.

Human T-cell leukemia virus type 1 (HTLV-1) is an etiologic agent of adult T-cell leukemia (ATL). A viral product, p40x, encoded by the pX sequence of HTLV-1 is a trans-acting transcriptional activator of the long terminal repeat (LTR) and has been suspected of involvement in leukemogenesis, activating the cellular genes. The cellular interleukin-2 (IL-2) and its receptor (IL-2R), the latter of which is expressed on ATL leukemic cells, were shown to be transiently induced by transfection of plasmid pMTPX expressing pX in two T-cell lines, Jurkat and HSB-2, but not in other human T- or B-cell lines. The cell type specificity of IL-2R induction by pX expression was the same as that by phytohaemagglutinin/phorbol ester activation, indicating the requirement for some specific cellular factors or a certain state of cellular differentiation. Induction of IL-2 and IL-2R at mRNA level was also demonstrated in transfected cells. Transfections with mutants of pMTPX in which the open reading frames for p40x, p27x-III and p21x-III were inactivated indicated that p40x alone was sufficient for induction of the IL-2R in inducible cells. This induction of the IL-2R by p40x of HTLV-1 may contribute to preferential proliferation of HTLV-1 infected cells at an early stage of ATL development and eventually increase the number of putative target cells for malignant transformation.

Cell Line↗
PubMed1986

Depression of protective mechanism during the early phase of a viral infection in tumor-bearing mice and prevention by PSK.

Effector mechanisms responsible for resistance against ectromelia virus including antiviral activity of non-immune macrophages, antiviral antibody, delayed footpad reaction to viral antigen, and interferon induction after viral infection were depressed in BALB/c mice bearing syngeneic Meth A tumor. The degree of viral growth correlated well with the depression of delayed footpad reaction, antibody production, and interferon induction. Therefore, modification of macrophage functions by a tumor-bearing state and treatment with PSK may contribute to this modification of antiviral resistance, at an early phase of infection. Cytotoxic activity may not be the principal effector, since the cytotoxicity was induced in normal and tumor-bearing mice to almost the same extent yet an extensive viral growth occurred only in the latter.

Animals↗
PubMed1986

[Changes in nonspecific suppressor factors in the serum of gastric cancer patients after surgery and immunochemotherapy].

After curative surgery for gastric cancers judged macroscopically to be at stage 2 or 3, patients were divided into 4 groups by randomization. As the basic treatment, patients were given one-shot Mitomycin and Tegafur as maintenance therapy for 8 months (group A). PSK (group B), OK-432 (group C) or both PSK and OK-432 (group D) were added to the treatment of group A for 8 months. Sera were obtained from these groups of patients at 4 weeks and 3, 6, 9 and 12 months after surgery. In all of these groups, values of IAP increased slightly at 4 weeks but decreased at 3 months and were maintained at such a level by 12 months. On the other hand, suppressive effects of such sera on the blastogenesis of murine spleen cells in response to PHA varied among these group. In groups A and C, the suppressive effect of sera increased after surgery and was detected continuously by 12 months. In groups B and D, in contrast, the suppressive effect disappeared from 3 to 12 months. The rise and fall of such a suppressive effect of sera may reflect the mode of action of PSK.

Female↗