The Experts below are selected from a list of 105 Experts worldwide ranked by ideXlab platform
Swapan K. Ghosh - One of the best experts on this subject based on the ideXlab platform.
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Extracellular Matrix from Porcine Small Intestinal Submucosa (SIS) as Immune Adjuvants
PloS one, 2011Co-Authors: Youssef Aachoui, Swapan K. GhoshAbstract:Porcine small intestinal submucosa (SIS) of Cook Biotech is licensed and widely used for tissue remodeling in humans. SIS was shown to be highly effective as an adjuvant in model studies with prostate and ovarian cancer vaccines. However, SIS adjuvanticity relative to alum, another important human-licensed adjuvant, has not yet been delineated in terms of activation of innate immunity via inflammasomes and boosting of antibody responses to soluble proteins and hapten-protein conjugates. We used ovalbumin, and a hapten-protein conjugate, phthalate-keyhole limpet hemocyanin. The evaluation of SIS was conducted in BALB/c and C57BL/6 mice using both intraperitoneal and subcutaneous routes. Inflammatory responses were studied by microarray profiling of chemokines and cytokines and by qPCR of inflammasomes-related genes. Results showed that SIS affected cytokine and chemokines microenvironments such as up-regulation of IL-4 and CD30-ligand and activation of Chemotactic Factors LIX and KC (neutrophil Chemotactic Factors), MCP-1 (monocytes Chemotactic Factors), MIP 1-α (Macrophage Chemotactic Factor) and lymphotactin, as well as, growth Factors like M-CSF. SIS also promoted gene expression of Nod-like receptors (NLR) and associated downstream effectors. However, in contrast to alum, SIS had no effects on pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) or NLRP3, but it appeared to promote both Th1 and Th2 responses under different conditions. Lastly, it was as effective as alum in engendering a lasting and specific antibody response, primarily of IgG1 type.
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Extracellular Matrix from Porcine Small Intestinal Submucosa (SIS) as Immune Adjuvants
2011Co-Authors: Youssef Aachoui, Swapan K. GhoshAbstract:Porcine small intestinal submucosa (SIS) of Cook Biotech is licensed and widely used for tissue remodeling in humans. SIS was shown to be highly effective as an adjuvant in model studies with prostate and ovarian cancer vaccines. However, SIS adjuvanticity relative to alum, another important human-licensed adjuvant, has not yet been delineated in terms of activation of innate immunity via inflammasomes and boosting of antibody responses to soluble proteins and haptenprotein conjugates. We used ovalbumin, and a hapten-protein conjugate, phthalate-keyhole limpet hemocyanin. The evaluation of SIS was conducted in BALB/c and C57BL/6 mice using both intraperitoneal and subcutaneous routes. Inflammatory responses were studied by microarray profiling of chemokines and cytokines and by qPCR of inflammasomesrelated genes. Results showed that SIS affected cytokine and chemokines microenvironments such as up-regulation of IL-4 and CD30-ligand and activation of Chemotactic Factors LIX and KC (neutrophil Chemotactic Factors), MCP-1 (monocytes Chemotactic Factors), MIP 1-a (Macrophage Chemotactic Factor) and lymphotactin, as well as, growth Factors like M-CSF. SIS also promoted gene expression of Nod-like receptors (NLR) and associated downstream effectors. However, in contrast to alum, SIS had no effects on pro-inflammatory cytokines (IL-6, IL-1b, TNF-a) or NLRP3, but it appeared to promote both Th1 and Th2 responses under different conditions. Lastly, it was as effective as alum in engendering a lasting and specifi
Youssef Aachoui - One of the best experts on this subject based on the ideXlab platform.
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Extracellular Matrix from Porcine Small Intestinal Submucosa (SIS) as Immune Adjuvants
PloS one, 2011Co-Authors: Youssef Aachoui, Swapan K. GhoshAbstract:Porcine small intestinal submucosa (SIS) of Cook Biotech is licensed and widely used for tissue remodeling in humans. SIS was shown to be highly effective as an adjuvant in model studies with prostate and ovarian cancer vaccines. However, SIS adjuvanticity relative to alum, another important human-licensed adjuvant, has not yet been delineated in terms of activation of innate immunity via inflammasomes and boosting of antibody responses to soluble proteins and hapten-protein conjugates. We used ovalbumin, and a hapten-protein conjugate, phthalate-keyhole limpet hemocyanin. The evaluation of SIS was conducted in BALB/c and C57BL/6 mice using both intraperitoneal and subcutaneous routes. Inflammatory responses were studied by microarray profiling of chemokines and cytokines and by qPCR of inflammasomes-related genes. Results showed that SIS affected cytokine and chemokines microenvironments such as up-regulation of IL-4 and CD30-ligand and activation of Chemotactic Factors LIX and KC (neutrophil Chemotactic Factors), MCP-1 (monocytes Chemotactic Factors), MIP 1-α (Macrophage Chemotactic Factor) and lymphotactin, as well as, growth Factors like M-CSF. SIS also promoted gene expression of Nod-like receptors (NLR) and associated downstream effectors. However, in contrast to alum, SIS had no effects on pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) or NLRP3, but it appeared to promote both Th1 and Th2 responses under different conditions. Lastly, it was as effective as alum in engendering a lasting and specific antibody response, primarily of IgG1 type.
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Extracellular Matrix from Porcine Small Intestinal Submucosa (SIS) as Immune Adjuvants
2011Co-Authors: Youssef Aachoui, Swapan K. GhoshAbstract:Porcine small intestinal submucosa (SIS) of Cook Biotech is licensed and widely used for tissue remodeling in humans. SIS was shown to be highly effective as an adjuvant in model studies with prostate and ovarian cancer vaccines. However, SIS adjuvanticity relative to alum, another important human-licensed adjuvant, has not yet been delineated in terms of activation of innate immunity via inflammasomes and boosting of antibody responses to soluble proteins and haptenprotein conjugates. We used ovalbumin, and a hapten-protein conjugate, phthalate-keyhole limpet hemocyanin. The evaluation of SIS was conducted in BALB/c and C57BL/6 mice using both intraperitoneal and subcutaneous routes. Inflammatory responses were studied by microarray profiling of chemokines and cytokines and by qPCR of inflammasomesrelated genes. Results showed that SIS affected cytokine and chemokines microenvironments such as up-regulation of IL-4 and CD30-ligand and activation of Chemotactic Factors LIX and KC (neutrophil Chemotactic Factors), MCP-1 (monocytes Chemotactic Factors), MIP 1-a (Macrophage Chemotactic Factor) and lymphotactin, as well as, growth Factors like M-CSF. SIS also promoted gene expression of Nod-like receptors (NLR) and associated downstream effectors. However, in contrast to alum, SIS had no effects on pro-inflammatory cytokines (IL-6, IL-1b, TNF-a) or NLRP3, but it appeared to promote both Th1 and Th2 responses under different conditions. Lastly, it was as effective as alum in engendering a lasting and specifi
Takusaburo Ebina - One of the best experts on this subject based on the ideXlab platform.
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Antitumor effect of a peptide-glucan preparation extracted from Agaricus blazei in a double-grafted tumor system in mice
Biotherapy, 1998Co-Authors: Takusaburo Ebina, Yoshiaki FujimiyaAbstract:The antitumor effect of extracts obtained from the fruit body of Agaricus blazei Murill was examined in a double-grafted tumor system, in which BALB/ c mice received simultaneous intradermal injections of Meth-A tumor cells in both the right (106 cells) and left flank (2 × 105 cells), and were then injected with 5 mg of extracts of A. blazei in the right tumor on days 3, 4 and 5. Intratumoral administration of ethanol-soluble (Fraction 1), water-ethanol-soluble (Fraction 2), ammonium oxalate-soluble (Fraction 3) and ammonium oxalate-insoluble (Fraction 4) fractions resulted in inhibition of tumor growth, with Fraction 3 showing the most tumoricidal activity, producing regression of the right tumor and inhibitition of growth of the left, non-injected tumor. The maximum effect was obtained using 0.5 mg of Fraction 3 and this amount was used in subsequent experiments. The antitumor effect of intratumorally administered Fraction 3 was enhanced by oral ad lib administration of feed containing 0.083% of Fraction 3. When immunized spleen cells from mice that had been cured by intratumoral administration of 0.5 mg of Fraction 3 were directly injected (2 × 107 cells/mouse) into the Meth-A tumor, tumor growth was inhibited. The tumor cells on day 7 from the Fraction 3-treated right tumor and from the left tumor were cultured for 24 h and their culture supernatants were assayed for neutrophil or Macrophage Chemotactic activity. Significant Macrophage Chemotactic Factor activity was detected in the culture media from the left tumor tissue. Serum levels of immunosuppressive acidic protein (IAP), produced by activated Macrophages and neutrophils, increased transiently soon after intradermal injection of 0.5 mg of Fraction 3. These results suggest that regression of the left non-injected tumor was due to an immune reaction, involving induction of cytotoxic cells in the spleen, and the release of Chemotactic Factors in the distant tumor.
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Antitumor effect of aColiolus preparation, PSK: Induction of Macrophage Chemotactic Factor (MCF) in spleens of tumor bearing mice
Biotherapy, 1992Co-Authors: Keiko Ishikawa, Toshiro Majima, Takusaburo EbinaAbstract:The effect of administration of PSK (Polysaccharide Kureha), a Coliolus preparation, in Meth-A solid tumors was analyzed in BALB/c mice. Spleen cells prepared from normal, non-treated Meth-A bearing, PSK-treated normal and PSK-treated tumor bearing mice were examined for induction of Macrophage Chemotactic Factor (MCF). Only spleen cells from the latter mice produced MCF after 48 hrs of cultivation in the presence of Meth-A cells or Concanavalin A (Con A). MCF-producing cells were indicated to be Lyt-1 positive, L3T4 positive and Lyt-2 negative cells in the negative elimination assay. There were no differences in the production of other cytokines including interleukin-2, inferferon and tumor necrosing Factor, spleen cells obtained other different groups of mice. The antitumor effect of either crude or purified MCF (molecular weight 100,000) was examined by daily consecutive intratumoral injections into Meth-A tumor tissues, and a significant inhibitory effect was detected.
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Antitumor effect of a Coliolus preparation, PSK: induction of Macrophage Chemotactic Factor (MCF) in spleens of tumor bearing mice.
Biotherapy (Dordrecht Netherlands), 1992Co-Authors: Keiko Ishikawa, Toshiro Majima, Takusaburo EbinaAbstract:The effect of administration of PSK (Polysaccharide Kureha), aColiolus preparation, in Meth-A solid tumors was analyzed in BALB/c mice. Spleen cells prepared from normal, non-treated Meth-A bearing, PSK-treated normal and PSK-treated tumor bearing mice were examined for induction of Macrophage Chemotactic Factor (MCF). Only spleen cells from the latter mice produced MCF after 48 hrs of cultivation in the presence of Meth-A cells or Concanavalin A (Con A). MCF-producing cells were indicated to be Lyt-1 positive, L3T4 positive and Lyt-2 negative cells in the negative elimination assay. There were no differences in the production of other cytokines including interleukin-2, inferferon and tumor necrosing Factor, spleen cells obtained other different groups of mice. The antitumor effect of either crude or purified MCF (molecular weight 100,000) was examined by daily consecutive intratumoral injections into Meth-A tumor tissues, and a significant inhibitory effect was detected.
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Differences of antitumor effect of various BRMs by intratumoral administration
Gan to kagaku ryoho. Cancer & chemotherapy, 1992Co-Authors: Takusaburo Ebina, Murata KAbstract:The antitumor effects of biological response modifiers (BRM) in a new experimental mouse model, the "double grafted tumor system", were analysed. BALB/c mice received simultaneous inoculations of Meth-A fibrosarcoma cells on right flank (10(6) cells) and left flank (2 x 10(5) cells) on day 0, and BRMs were injected intratumorally into right tumor on day 3, 4 and 5. The growth of the left-flank tumor was the real target for the evaluation of a given drug after 21 days. PSK (a protein-bound polysaccharide preparation), IL-1 and Cepharanthin cured not only the right, but also the left, non-treated tumor in a double grafted tumor system. OK-432 (a Streptococcus preparation) and BCG cured the right tumor and inhibited the growth of the left tumor. Lentinan (a polysaccharide preparation) inhibited neither the right nor the left tumor. Spleen cells from PSK-treated tumor bearing mice produced Macrophage Chemotactic Factor (MCF) after 48 hrs cultivation in the presence of Con A or Meth-A tumor cells. MCF producing cells were indicated to be L3T4 positive cells. On the other hand, PMN activated by PSK treatment produced MCF in the culture supernatant. Therefore, our present and previous studies on the antitumor effect of BRM in the double grafted tumor system show that intratumoral administration of BRM first induces neurophils in the right tumor via an IL-8-like Factor and then cytotoxic Macrophages are induced by MCF. Then Lyt-1 (L3T4)-positive cells are induced in the right regional lymph nodes and in the spleen, probably via IL-1, which might be produced from Macrophages in contact with tumor cells. Subsequently, Lyt-1-positive cells reach the left tumor through the blood stream, come into contact with Meth-A tumors and then produce MCF. Intratumoral administration of PSK in the right tumor thus induces cytotoxic Macrophages in the left, non-treated tumor, thereby bringing about the regression of the distant tumor.
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Antitumor Effector mechanism of plant alkaloid preparation, cepharanthin, by intratumoral administration
Gan to kagaku ryoho. Cancer & chemotherapy, 1991Co-Authors: Takusaburo Ebina, Kazuko MurataAbstract:The antitumor effect of biscoclaurine alkaloids, at a distant site was examined in the double grafted tumor system, in which mice received simultaneous intradermal inoculations of Meth-A in both right (10(6) cells) and left (2 x 10(5) cells) flanks and were then injected with 0.5 mg of CR in the right tumor on days 3, 4 and 5. CR inhibited the growth of not only the right but also the left, non-treated tumor. In order to examine the role of lymph nodes in the antitumor activity of CR, regional (axillary and inguinal) lymph nodes were resected. Since in resected mice the antitumor activity of CR against the left tumor was weakened, the regional lymph nodes have a very important role in the antitumor effect of intratumoral administration of CR at a distant site. Spleen cells prepared from CR treated mice were examined for Lyt-1, Lyt-2 and L3T4 phenotypes. The number of Lyt-1 positive lymphocytes increased in the spleen after intratumoral administration of CR. Isolated tumor cells obtained from the right tumor treated with CR and the left side tumor on day 6 were cultured for 24 h. The culture supernatants were harvested and tested for the presence of Chemotactic activity for neutrophil or Macrophage. Significant neutrophil Chemotactic Factor (NCF) activity was detected in the culture media from CR-treated right tumor tissue, and Macrophage Chemotactic Factor (MCF) activity was detected in the culture media from left tumor tissue. CR-induced NCF was partially neutralized by treatment with anti-human IL-8 IgG, and might be murine IL-8 Factor. These results suggest that intratumoral administration of CR first induces neutrophils in the right tumor, then Lyt-1 positive cells in the spleen, and subsequently induces cytotoxic Macrophages in the left, non-treated tumor, thus bringing about the regression of distant tumors.
Yoshiro Kobayashi - One of the best experts on this subject based on the ideXlab platform.
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Phenotypic Properties and Cytokine Production of Skin-Infiltrating Cells Obtained from Guinea Pig Delayed-Type Hypersensitivity Reaction Sites
Cellular Immunology, 1995Co-Authors: Nobuaki Higashi, Naonobu Yoshizuka, Yoshiro KobayashiAbstract:Abstract In this study, skin-infiltrating cells were prepared from guinea pig delayed-type hypersensitivity reaction sites, and their phenotypic properties and cytokine production were examined. Our cell preparations contained around 45% nonspecific esterase-positive cells and a few skin-derived cells. Skin-infiltrating cells produced TNF activity and Macrophage Chemotactic activity (MCA), whereas resident skin cells produced much lower activity. The highest TNF activity was produced by skin-infiltrating cells at 2 hr after antigen injection. In contrast, a larger amount of MCA was produced by skin-infiltrating cells at 24 and 48 hr than at 2 hr after antigen injection. These kinetics were in good agreement with our previous results regarding cytokine activity in skin extracts. Gel filtration analysis and neutralization assay with a monoclonal antibody against human Macrophage Chemotactic Factor with a molecular weight of 1 kDa (MCF-1) indicated that a guinea pig homologue of human MCF-1 was partially responsible for the MCA.
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Involvement of Inflammatory Cytokines in a Delayed-Type Hypersensitivity Reaction
Cellular immunology, 1995Co-Authors: Nobuaki Higashi, Naonobu Yoshizuka, Toshiaki Osawa, Atsushi Ohuchi, Yoshiro KobayashiAbstract:We previously reported the amino acid sequence of the human Macrophage Chemotactic Factor with a molecular weight of 1000 (MCF-1) was WLGREDGSE. In this study we examined the roles of MCF-1 and tumor necrosis Factor (TNF) in a guinea pig delayed-type hypersensitivity (DTH) reaction. When Macrophage Chemotactic activity (MCA) in a skin extract was subjected to gel filtration, only the activity with a molecular weight of 1000 was significantly inhibited by anti-human MCF-1 mAb (7-3 mAb). Both MCA and TNF activity were detected in skin extracts from DTH inflammation sites where the specific antigen was injected. Both activities were produced at the early DTH reaction stage. In contrast, MCF-1 was produced at the late DTH reaction stage. The erythema was suppressed significantly either by anti-guinea pig TNF Ab or by 7-3 mAb, suggesting the roles of these two cytokines in a DTH reaction.
M Mitsuyama - One of the best experts on this subject based on the ideXlab platform.
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Difference in the functional maturation of T cells against Listeria monocytogenes in lymph nodes and spleen.
Immunology, 1992Co-Authors: B A Serushago, T Handa, M Mitsuyama, K Muramori, Toshitaka Koga, Kikuo NomotoAbstract:After subcutaneous immunization of mice with viable Listeria monocytogenes (LM), we evaluated the function of T cells induced in draining lymph nodes (LN) and spleen as determined by the local transfer of delayed-type hypersensitivity (DTH), acquired cellular resistance (ACR) and in vitro lymphokine production. LN cells could transfer specifically DTH but not ACR. In contrast, spleen cells from the same donor mice evoked the DTH response as well as bacterial clearance at the reaction site. Comparison of bacterial counts in spleen and in LN upon subcutaneous inoculation of mice with LM suggested that the lack of bacterial proliferation in LN underlay the failure to induce protective T cells in this lymphoid tissue. Spleen and LN T cells expressed CD4 and CD8 surface antigens equally and DTH response was solely dependent on CD4+ cells. Another major difference between LN and spleen cells was the profile of lymphokines produced in vitro. Upon the in vitro restimulation with killed Listeria, immune spleen cells produced Macrophage Chemotactic Factor (MCF), interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). In contrast, LN cells could produce all of the measured lymphokines but not IFN-gamma. The results provided strong evidence for the dissociation of DTH and ACR. Listerial growth appeared to be the requirement for full maturation of anti-listerial immunity that may coincide with the generation of IFN-gamma-producing T cells.
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A dissociated induction of MCF-producing and MAF-producing T cells specific for Listeria monocytogenes in the in vitro primary culture system.
Immunology, 1991Co-Authors: K Muramori, T Handa, M Mitsuyama, B A Serushago, K NomotoAbstract:Using an in vitro primary culture system which we had previously established, the induction phase of Listeria monocytogenes-specific effector cells was analysed with respect to their abilities to produce effector lymphokines, Macrophage Chemotactic Factor (MCF) and Macrophage-activating Factor (MAF). Listeria-specific effector cells generated after in vitro culture of normal spleen cells with viable L. monocytogenes for 5 days conveyed L3T4+, Lyt-2-, Thy-1+ surface antigens and produced MCF and MAF in response to the secondary stimulation with heat-killed L. monocytogenes. The cells required for the induction of Listeria-specific effector cells, which produce effector lymphokines, MCF and MAF, were L3T4+, Lyt-2-, Thy-1+ cells. The kinetic analysis revealed that the ability of these effector cells to produce MCF was generated earlier than that to produce MAF. Furthermore, using passive transfer of cells, the effector cells producing only MCF, which were generated early in culture, conferred delayed-type hypersensitivity (DTH) alone, but MCF- and MAF-producing effector cells generated late in culture conferred sufficient levels of DTH and acquired cellular resistance (ACR). These results indicate a dissociated production of MCF and MAF by L. monocytogenes-specific T cells generated in the primary in vitro culture system.
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Dissociated development of T cells mediating delayed-type hypersensitivity and protective T cells against Listeria monocytogenes and their functional difference in lymphokine production.
Infection and immunity, 1991Co-Authors: Hiroki Tsukada, Kikuo Nomoto, Ikuo Kawamura, Masaaki Arakawa, M MitsuyamaAbstract:CD4+ T cells mediating both delayed-type hypersensitivity (DTH) and acquired cellular resistance (ACR) were generated in mice after immunization with viable Listeria monocytogenes. In contrast, CD4+ T cells from mice immunized with killed L. monocytogenes in complete Freund's adjuvant were capable of mediating only DTH but not ACR. To determine the functional difference between T cells mediating DTH and T cells mediating ACR, we examined two different populations of T cells for profiles of lymphokine production after stimulation with a specific antigen in vitro. The production of interleukin-2 (IL-2) and IL-3 but not IL-4 was observed in both T cells mediating only DTH and those mediating DTH and ACR. In this respect, both types of T cells could be categorized into the TH1 population, and they produced Macrophage Chemotactic Factor equally well. However, the production of gamma interferon (IFN-gamma) was observed only in T cells capable of mediating both DTH and ACR. This result was confirmed not only by an enzyme immunoassay specific for murine IFN-gamma but also by Northern (RNA) analysis for the detection of IFN-gamma mRNA. These results suggested that the TH1 population may be subdivided further into two distinct subsets and that the ineffectiveness of the killed bacterial vaccine may be partly explained by the dissociated development of T cell function.
