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Biomedical subjects

S Tsuru

Publications and source records attributed to S Tsuru.

At least 91 records · Page 5Linked to original sources

Antitumor activity of protein-bound polysaccharide from Cordyceps ophioglossoides in mice.

The effects of protein-bound polysaccharide (SN-C) extracted from Cordyceps ophioglossoides on the growth of transplanted allogeneic and syngeneic murine tumors were studied. SN-C given by intraperitoneal administration suppressed the growth of sarcoma-180 transplanted subcutaneously in mice. Intraperitoneal administration of SN-C also caused a significant prolongation of the life span of ICR mice inoculated intraperitoneally with Ehrlich carcinoma, and C3H/He mice inoculated intraperitoneally with a syngeneic tumor (X-5563). SN-C showed a significant cytocidal effect on cultured tumor cells. SN-C did not affect delayed-type hypersensitivity (DTH) in normal mice, but restored the depressed capacity to raise DTH in tumor-bearing mice. These results suggested that SN-C may exert both direct and host-mediated antitumor effects.

Animals↗

Immune protective mechanisms during pregnancy. I. Cell-mediated immunity against Listeria monocytogenes in pregnant mice.

Characteristics of protective mechanisms during pregnancy were investigated using neonatally thymectomized (NTx) and/or pregnant mice infected with sublethal doses of Listeria monocytogenes, of which the explosive growth at an early phase of 2 or 3 days after infection is prevented by non-immune macrophages, and complete elimination at a late phase from 4 to 10 days after infection is attributed to the augmented functions of macrophages in co-operation with lymphokine-producing sensitized T lymphocytes. Although in virgin control mice there was a gradual decline of bacteria from the day after infection, viable bacteria in pregnant mice showed an increase in number until Day 3. In such pregnant mice, carbon clearance was suppressed. Thus, the enhanced bacterial growth in pregnant mice within 3 days may be attributable to the suppressed functions of non-immune macrophages. Complete elimination of Listeria from Day 4 was observed in pregnant sham-operated mice as well as in non-pregnant and pregnant NTx mice. Twenty-four hour reaction of delayed-type in normal mice induced by sheep red blood cells (SRBC) in incomplete Freund's adjuvant (IFA) was not affected by pregnancy, while 48 hr reaction in mice immunized with SRBC in complete Freund's adjuvant (CFA) was suppressed by pregnancy. We have reported previously that macrophage migration inhibitory factor (MIF) was produced in the latter but not in the former, and that the tuberculin type of delayed hypersensitivity accompanied by MIF production scarcely participated in acquired resistance to Listeria. Effective elimination of Listeria in pregnant and/or NTx mice at a late phase may be attributable to the activity of cellular immunity comparable to 24 hr reaction. These results suggest that T cells showing a low degree of thymus dependency in the ontogenic development may be the major component required for acquired protective immunity against Listeria and may account for the protection in pregnant mice.

Animals↗

Response of bacterial antigen in palmoplantar pustulosis.

Motilities of leukocytes in response to bacterial antigens or sera were examined in tissues from patients with palmoplantar pustulosis (PPP). Accelerated migration towards bacterial antigens was detected in the case of Staphylococcus epidermidis in 9 of 19 patients, to Propionibacterium acnes in 5 of 19, to Proteus mirabilis and Staphylococcus aureus in 3 of 19, while no acceleration was found in neutrophils from the controls. A significantly accelerated migration of normal lymphocytes in response to both patients' and control sera was nil. Inhibition of migration of guinea pig peritoneal exudate cells mixed with lymphocytes from PPP patients was detected in 12 out of 14 patients with the addition of S. epidermidis antigen and 8 of 14 with the addition of P. acnes antigen, while no such inhibition was detected in all 7 controls. The accelerated migration of neutrophils and inhibition of macrophages may participate in the development of PPP.

Adult↗

Immunological studies on Crohn's disease. V. Enumeration of circulating lymphocytes subsets using monoclonal antibodies.

We found normal levels of suppressor cell activity and reduced natural killer (NK) and antibody dependent cell-mediated cytotoxicity (ADCC) activities in patients with Crohn's disease (CD). To further characterize these activities, studies were carried out using monoclonal antibodies. There were no changes in the proportion of OKT4+ (helper/inducer T cells), OKT8+ or Leu 2+ (suppressor/cytotoxic T cells) and Leu 7+ (large granular lymphocytes: LGL, NK + K cells), thereby suggesting that suppressor cell activity in CD is likely to be normal both in function and in number, and that depressed NK and ADCC activities are not due to a reduction in the number of NK or K cells but rather to functional defects. Using a double staining method, we noted a low percentage of both Leu 2 and Leu 7 positive cells in CD.

Antibodies, Monoclonal↗

[Augmentation of resistance against metastatic tumor cells after local administration of PSK].

Local administration of PSK augmented the generation of cytotoxic lymphocytes and the induction of resistance against metastatic tumor. Augmented generation of cytotoxic lymphocytes may be ascribed to local effects of PSK in the lymph nodes, since this is mediated by Lyt-1+2+ cells. Local administration of PSK increased the threshold number of metastatic tumors eliminated by 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.

Adjuvants, Immunologic↗

Mechanisms of in vivo generation of cytotoxic activity against syngeneic tumours. I. Local differentiation of mature cytotoxic T lymphocytes in the rejection of tumours.

Mature cytotoxic T lymphocytes (CTL) were detected in the peritoneal cavity of syngeneic mice immunized intraperitoneally (i.p.) with mitomycin C (MC)-treated EL-4 or X5563 cells, but were not found in their spleens or lymph nodes. Mature CTL appeared among PE cells after transfer of spleen cells from those immune mice, along with MC-treated tumour cells, to the peritoneal cavity of syngeneic mice. These results lead us to the hypothesis that immature CTL primed in the spleen and lymph nodes may migrate to the site of tumour inoculation and differentiate into mature CTL after antigenic or non-specific stimulation at that site. Inability of primed CTL to differentiate to mature CTL in the spleen might be explained by the effect of splenic suppressor cells, since mature CTL became detectable in the spleen of immune mice by treatment with cyclophosphamide.

Animals↗

Demonstration and characterization of immunosuppressive factors in sera from patients with Crohn's disease.

The effect of sera from 17 patients with Crohn's disease, 8 with ulcerative colitis or 5 with intestinal tuberculosis on the proliferative response of mouse spleen cells induced by phytohemagglutinin (PHA) was studied. Sera from patients with Crohn's disease markedly suppressed the blastogenesis of mouse spleen cells (S.I. = 6.8 +/- 2.0, % suppression = 83%), as compared with normal sera (S.I. = 41.0 +/- 5.2, p less than 0.001, % suppression = 0). Conversely, ulcerative colitis sera did not suppress the blastogenesis of mouse spleen cells (S.I. = 43.5 +/- 8.7, % suppression = -6%), nor the sera of intestinal tuberculosis (S.I. = 38.9 +/- 4.0, % suppression = 6%). Thus, we confirmed the possible existence of immunosuppressive factors in Crohn's disease. Moreover, immunosuppressive factors in Crohn's disease were characterized for biochemical properties. The approximate molecular weight is 45,000 estimated by diafiltration and gel filtration on a Sephadex G-75 column. Analytical isoelectric focusing showed an increased amount of acidic protein in fractionated sera (m.w. ranging 30,000-50,000) from patients with Crohn's disease and ulcerative colitis, in comparison with that in normal sera. Furthermore, the main peak of this acidic protein in Crohn's disease was an isoelectric point (pI) of 2.8, while the pI of that from ulcerative colitis was 3.0. These results suggest that qualitative differences of such acidic protein may serve to discriminate between the sera of Crohn's disease and ulcerative colitis.

Adolescent↗

Depression of macrophage functions and T-cell-mediated immunity to listeria infection in tumor-bearing mice and its prevention by PSK.

The effect of PSK on the depressed bactericidal activity of macrophages and delayed-type hypersensitivity (DTH) to Listeria monocytogenes in BALB/c mice bearing transplantable Meth A fibrosarcoma was studied. In tumor-bearing mice pretreated with PSK, L. monocytogenes was cleared rapidly from the circulating blood and bacterial growth in the liver was inhibited effectively in the early phase of infection. This resistance to the infection could be transferred with adherent peritoneal exudate cells (PEC) but not with nonadherent or adherent spleen cells of PSK-treated mice. In the early phase of infection, tumor-bearing mice developed a lower level of DTH to L. monocytogenes than nongrafted control mice. However, the control levels of DTH could be obtained by pretreatment with PSK in tumor-bearing mice. These results suggest that the restoration of DTH to L. monocytogenes by pretreatment with PSK may be attributable to the restoration of the depressed immunological responsiveness to the normal levels in tumor-bearing mice.

Animals↗

Cholera toxin-binding T cells in the human peripheral blood at different ages.

The capacity of human T cells to bind cholera toxin was shown to decrease with age. In aged humans, the number of cells capable of binding high concentrations of cholera toxin was lower than that in young humans. The method presented in this paper may be useful as one of the indicators of aging of the immune system.

Adolescent↗

Separation of osteoblast-like cells from bone marrow by fluorescence-activated cell sorting.

The purification of the osteoblast-like cells (2-3%) among the bone marrow cells (BMC) of C57BL/6 mice using a specific anti-osteoblast serum and a fluorescence-activated cell sorter is described. The antiserum was raised against osteoblast cells isolated from calvaria from neonatal mice. The majority of the cells of the osteoblast-enriched fraction from bone marrow showed a parathormone-induced increase in cyclic adenine monophosphate but no response to calcitonin. This is similar to the response of osteoblast cells obtained from the calvaria. Electron microscopic studies of the extracellular matrix of cultured osteoblast-like cells purified from bone marrow showed the deposition of apatite crystals within and in close apposition to the vesicles. These findings suggest that the isolated cell population was enriched in osteoblasts. Such a cell system from bone marrow might provide an experimental system for investigating the mechanism of bone formation.

Animals↗

Entrance of cholera enterotoxin subunits into thymus cells.

Analysis of the staining of cholera enterotoxin on the surface of cells with specific antibodies against each subunit of cholera enterotoxin, using a fluorescence-activated cell sorter and electron microscopy, showed that not only subunit A but also subunit B penetrates the cell membrane. The detection of subunits inside the cell was facilitated by the use of saponin, an agent that increases membrane permeability.

Animals↗

Effect of PSK on interferon production in tumor-bearing mice.

The effect of PSK on the depressed interferon (IF) production in tumor-bearing mice was studied. In tumor-bearing mice, in vitro IF production by spleen cells treated with polyinosinic-polycytidylic acid (poly I:C) was remarkably inhibited. However, these inhibitions were prevented by the intraperitoneal (ip) administration of PSK. Mice were inoculated intravenously (iv) with poly I:C-treated spleen cells, administered with PSK ip at 3 days after the tumor inoculation. When PSK was not given, poly I:C-treated spleen cells did not show an inhibitory effect on tumor growth. In mice given PSK ip, poly I:C-treated spleen cells exerted slightly inhibiting effects on tumor growth. These results suggest that PSK prevented such a modulation in tumor-bearing mice.

Animals↗

[Depression of protective mechanisms against ectromelia virus infection in tumor-bearing mice and its prevention by PSK].

Effector mechanisms responsible for protection against ectromelia virus (EMV) including antiviral activity of non-immune macrophages, cytotoxic T cells, antiviral antibody, delayed footpad reaction to viral antigen and interferon induction after viral infection were depressed in BALB/c mice bearing syngeneic Meth A tumors. The degree of viral growth correlated well with the depression of delayed footpad reaction, antibody production and interferon induction. But a control level of these elements could be obtained by pretreatment of tumor-bearing mice, with PSK Cytotoxic activity may not be the principal effector, since cytotoxicity was induced in both normal and tumor-bearing mice to almost the same extent but an explosive viral growth was observed only in the latter. These results suggest that PSK was responsible for restoring the depressed antiviral protective immunity to normal levels in tumor-bearing animals.

Adjuvants, Immunologic↗

[Effect of PSK on the recovery of macrophage function and T cell-mediated immunity in tumor-bearing mice].

The effect of PSK on the depressed bactericidal activity of macrophages and delayed-type hypersensitivity (DTH) to Listeria monocytogenes in BALB/c mice bearing transplantable Meth A fibrosarcoma was studied. In tumor-bearing mice pretreated with PSK, L. monocytogenes was cleared rapidly from the circulating blood and bacterial growth in the liver was inhibited effectively in the early phase of infection. This resistance to the infection could be transferred with peritoneal exudate cells (PEC) but not with non-adherent PE cells of PSK-treated mice. In the early phase of infection, tumor-bearing mice developed a lower level of DTH to L. monocytogenes than did nongrafted control mice. However, the control levels of DTH could be obtained by pretreatment of tumor-bearing mice with PSK. These results suggest that the restoration of resistance to L. monocytogenes in tumor-bearing mice by PSK may be ascribed to both prevention of depression or activation of macrophage function and prevention of depression of T cell-mediated immunity.

Animals↗

Relationship between bactericidal and phagocytic activities of peritoneal macrophages induced by irritants.

Cellular accumulation to the peritoneal cavity and modification of various functions of peritoneal macrophages were observed in mice injected intraperitoneally (ip) with thioglycollate medium (TG), liquid paraffin, proteose peptone and Corynebacterium parvum. The cellular composition of peritoneal exudates at 4 days after injection of irritants was almost the same in all the groups and the proportion of macrophages was increased approximately 4 times more than nontreated controls. The ability to kill Listeria monocytogenes and to generate chemiluminescence (CL) were augmented strongly in C. parvum-induced macrophages, while depressed in TG-induced macrophages. The activities of liquid paraffin- or proteose peptone-induced macrophages were almost the same as those in nontreated controls. However, the ability to phagocytose native sheep erythrocytes was greatly augmented both in C. parvum- and TG-induced macrophages. There is thus a discrepancy between bactericidal activity and phagocytic activity among macrophages induced with various irritants.

Animals↗

Characterization of thymus cells in hyperplastic thymuses in patients with myasthenia gravis and ulcerative colitis with monoclonal antibodies.

Recently, increasing attention has been paid to thymic relevance to pathogenesis in some autoimmune diseases. In this report, the thymus cells from 7 patients with myasthenia gravis (MG) and 6 patients with ulcerative colitis (UC), who had undergone thymectomy for complication of thymic hyperplasia, were studied. The thymus cells were characterized with monoclonal antibodies (Anti-Leu-2a and Anti-Leu-3a) which define human T-cell surface antigens. Although the control thymus consisted of 82-94% of thymocytes which were reactive with Anti-Leu-2a and 90-95% of cells reactive with Anti-Leu-3a, in UC patients both Leu-2a positive thymus cells (38-56%) and Leu-3a positive cells (68-82%) were decreased. Concerning MG thymocytes, Leu-2a positive cells were also decreased (66-81%), but the percentage of Leu-3a positive cells did not show a remarkable change (86-90%) compared with control thymocytes. Considering the above results and many reports telling functional and populational abnormalities of peripheral immunocompetent cells, the process of intra-thymic T-cell maturation may be impaired in these autoimmune diseases.

Adult↗