[Cholera research 100 years after its discovery--current topics].
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Adenylyl Cyclases↗
Biomedical subjects
Y Zinnaka
Publications and source records attributed to Y Zinnaka.
[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↗
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↗
[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↗
Effects of cyclic AMP on in vivo cytotoxic T lymphocytes generation.
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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↗
Synthesis of glucan on the cell surface of Streptococcus mutans: chemical and scanning electron microscopic studies.
The appearance and continuing growth of extracellular material on Streptococcus mutans HS6 cells in sucrose-containing Merthiolated buffer was observed in a scanning electron microscope and was found to be related to the glucan synthesis on the cell and to adherence of the cell to a smooth surface. Cells grown in broth completely deprived of sucrose by invertase (HS6-IV) had a characteristic, slightly rugged surface structure. On incubation of HS6-IV in the sucrose-containing buffer, a few small globular particles appeared on the surface and grew to an irregular shape (globular to fibrilar) after several hours. The increase in the total glucan content of the cells paralleled the growth of the globular material, to which ferritin-conjugated anti-dextran globulin was found to bind. On the cell surface of cells harvested from conventional broth, both small globular and irregular structures, which possibly formed from sucrose in the broth, existed originally and continued to grow during incubation, along with the material newly appearing on the surface. The accumulation of glucan on the cells resulted in their adherence to a glass surface. The inhibition of growth of the extracellular material on the cells by trypsin, dextranase or anti-glucosyltransferase corresponded to the decrease in glucan synthesis and the loss of adhering ability. These results indicated that the material growing on the cell surface was glucan synthesized by glucosyltransferases.
Adhesiveness↗
[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↗
Importance of polymorphonuclear leucocytes in protection of mice against Escherichia coli.
Bacterial growth and lethality of Escherichia coli infection of mice were enhanced by X-irradiation but not by treatment with carrageenan. Since carrageenan depletes macrophages but not polymorphonuclear leucocytes, it is concluded that protection against E. coli, at least in the early phases, depends mainly on polymorphonuclear leucocytes.
Animals↗
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↗