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Toshihiko Hirano – 1st expert on this subject based on the ideXlab platform

  • Promotion of Lymphocyte Blastogenesis by Hemodialysate of Chronic Renal Failure
    Nephron, 2008
    Co-Authors: Toshihiko Hirano, Yasuharu Toyoshima, Tohru Tamaki, Masami Kozaki


    Effects of hemodialysate of patients with chronic renal failure (CRF) on Blastogenesis of human peripheral blood lymphocytes in the presence of concanavalin A or phytohemagglutinin was investigated. H

  • comparison of suppressive potency between azathioprine and 6 mercaptopurine against mitogen induced Blastogenesis of human peripheral blood mononuclear cells in vitro
    Journal of Pharmacy and Pharmacology, 2003
    Co-Authors: Kentaro Sugiyama, Hiroshi Satoh, Toshihiko Hirano


    : Azathioprine (AZ) is a prodrug of 6-mercaptopurine (6-MP), but little is known about the relative suppressive efficacy of these agents against Blastogenesis of human peripheral blood mononuclear cells (PBMCs) in-vitro. We compared the pharmacological efficacy of AZ and 6-MP against T cell mitogen-induced Blastogenesis of PBMCs in-vitro. PBMCs were obtained from seven healthy subjects. The potency of AZ and 6-MP to suppress PBMC-Blastogenesis in-vitro was compared using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay procedures. Production of 6-MP from AZ in PBMC culture was examined by high-performance liquid chromatography. Both AZ and 6-MP dose-dependently suppressed PBMC Blastogenesis. Mean +/- s.d. IC50 (concentration of drug that gave 50% inhibition) values for AZ and 6-MP were 230.4 +/- 231.3 and 149.5 +/- 124.9 nM, respectively. Thus, the potencies of AZ and 6-MP to suppress PBMC Blastogenesis were not significantly different. A significant correlation was observed between the IC50 values of AZ and 6-MP (P < 0.01, n = 6). After incubation of PBMCs with 100 microM AZ for 4 days, 35.3-92.5 microM 6-MP was liberated into the culture medium. The ratio of 6-MP liberation from AZ was influenced by the presence of PBMCs, but not by the medium or fetal bovine serum. The results suggest that the suppressive potency of the prodrug AZ and its converted form 6-MP against Blastogenesis of human PBMCs in-vitro is similar, although PBMCs appeared to convert AZ to 6-MP. AZ is suggested to be effective after conversion to 6-MP to express immunosuppressive efficacy in-vitro.

  • gramicidin as a potential immunosuppressant for organ transplantation suppression of human lymphocyte Blastogenesis in vitro and prolongation of heart allograft survival in the rat
    Journal of Pharmacology and Experimental Therapeutics, 1995
    Co-Authors: Toshihiko Hirano, T Tamaki


    Linear polypeptide antibiotic gramicidin is known to interact with the cell membrane and deregulate cation exchange. Because perturbation of cell membrane function may suppress the immune cell network, the authors investigated the effects of gramicidin on lymphocyte Blastogenesis in vitro and allograft survival in vivo. Gramicidin blocked Blastogenesis of human peripheral blood lymphocytes that responded to mitogens (IC50 = 0.2-10.1 ng/ml) or allogeneic lymphocytes (IC50 = 4.9 ng/ml). The extent of these suppressive effects was equal to or superior to that of cyclosporine or prednisolone. The antibiotic caused no apparent cytotoxicity at a dose of 10,000 ng/ml. The suppression of lymphocyte Blastogenesis in vitro by cyclosporine or prednisolone was restored by addition of interleukin (IL)-1, IL-2, IL-4, IL-5 or IL-6. In contrast, none of these cytokines affected the suppressive activity of gramicidin on lymphocyte Blastogenesis. The immunosuppressive efficacy of gramicidin was further examined in vivo in heterotopically heart-transplanted rats. A heart graft from (Lewis x BN) F1 donor was implanted in the neck of allogeneic Lewis rats. In this model, beating of the graft in control recipients (placebo group) stopped as a result of acute allograft rejection at 5.4 +/- 0.4 days after transplantation (n = 38), whereas beating of the graft in recipients that received 2.0 or 4.0 mg kg-1 day-1 of gramicidin i.p. for 6 days was significantly prolonged to 15.4 +/- 4.3 (n = 5) or 18.4 +/- 3.9 (n = 5) days after transplantation, respectively (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

H D Johnson – 2nd expert on this subject based on the ideXlab platform

  • suppressed peripheral blood lymphocyte Blastogenesis in pre and postpartal sheep by chronic heat stress and suppressive property of heat stressed sheep serum on lymphocytes
    Developmental and Comparative Immunology, 1990
    Co-Authors: Y Niwano, B A Becker, Ranadhir Mitra, C W Caldwell, E B Abdalla, H D Johnson


    Abstract Phytohemagglutinin (PHA) and concanavalin A (Con A)-induced Blastogenesis of peripheral blood lymphocytes was examined in heat-stressed pre- and postpartal sheep. The peak responses of lymphocytes to PHA and Con A in heat-stressed sheep revealed significant reduction before and after parturition compared with those in the corresponding control animals kept under thermoneutral conditions. Furthermore, the effect of serum from control or heat-stressed sheep on PHA-induced lymphocyte Blastogenesis was examined. Supplementation of serum from heat-stressed sheep significantly suppressed the Blastogenesis of lymphocytes obtained from healthy sheep, bovine, and human donors. Unlike dexamethasone, heat-stressed sheep serum did not inhibit IL-2 production by PHA-stimulated human peripheral blood lymphocytes. These results indicate that the immunosuppression of heat-stressed sheep is in part mediated by serum factor(s) that can modulate T-cell function in a species nonspecific manner.

Michael K Robinson – 3rd expert on this subject based on the ideXlab platform

  • use of an optimized in vitro lymphocyte Blastogenesis assay to detect contact sensitivity to nickel sulfate in mice
    Toxicology and Applied Pharmacology, 1990
    Co-Authors: Michael K Robinson, D L Sneller


    Abstract This study was designed to determine whether an optimized in vitro lymphocyte Blastogenesis assay for identification of strong contact sensitizers would also detect sensitization to the weaker, clinically relevant allergen nickel sulfate (NiSO4). Though NiSO4 is effective in eliciting allergic skin reactions in patients sensitized to nickel-containing metals, it has been difficult to assess its potential to induce sensitization using standard or developmental in vivo animal tests. In vitro lymphocyte Blastogenesis has been useful in the diagnosis of nickel allergy in humans, but has not been applied to predictive testing in animals. We used a previously optimized lymphocyte Blastogenesis assay to determine whether lymphocytes from NiSO4-treated mice would exhibit NiSO4-specific proliferation and whether this would correlate with an in vivo ear swelling response. BALB/c mice given repeated open induction applications of NiSO4 were ear challenged, then lymphocytes from the draining nodes were cultured with Langerhans cell-enriched epidermal cells (EC), EC + soluble NiSO4, or NiSO4-modified EC (modified by preincubation with NiSO4). The NiSO4-modified EC stimulated significant NiSO4-specific specific proliferation. EC + soluble NiSO4 stimulated a nonspecific blastogenic response in lymphocytes from both NiSO4-treated and naive mice. There was no ear swelling response to NiSO4 using standard challenge procedures. However, exaggeration of the challenge procedure by gently abrading the ears just prior to NiSO4 application resulted in significant ear swelling, thereby supporting the conclusion that the in vitro results were indicative of in vivo sensitization.

  • an optimized lymphocyte Blastogenesis assay for detecting the response of contact sensitized or photosensitized lymphocytes to hapten or photohapten modified antigen presenting cells
    Toxicology in Vitro, 1990
    Co-Authors: G F Gerberick, Cindy A Ryan, E R Fletcher, D L Sneller, Michael K Robinson


    Abstract In vitro assays for predictive identification of contact sensitizers of photosensitizers are more quantifiable than current skin test methods and have the potential to reduce animal use. Mice were sensitized to various strong contact allergens, then an optimized lymphocyte Blastogenesis assay was used for detecting the proliferation of lymph node lymphocytes from those mice in response to soluble antigen or hapten-modified antigen presenting cells in culture. In vivo sensitization to oxazolone (OXAZ), a prototype sensitizer, resulted in poor in vitro lymphocyte Blastogenesis to a solubilized OXAZ preparation. To increase the assay sensitivity, dendritic cells from the draining lymph nodes of OXAZ-painted mice or OXAZ-modified Langerhans cell-enriched cultured epidermal cells (EC) were used as antigen presenting cells. This increased the OXAZ-specific response greater than 10-fold and 50-fold, respectively. This approach has since been used to demonstrate significant, albeit smaller, responses to weaker contact allergens such as nickel sulphate. EC were also used as antigen-presenting cells for in vitro lymphocyte Blastogenesis assays designed to detect photoallergens. Lymphocytes from mice photosensitized to tetrachlorosalicylanilide (TCSA) showed a significantly increased response to EC previously photohapten-modified by treatment with TCSA plus ultraviolet A (UVA), as compared with lymphocytes cultured with EC treated with TCSA but no UVA. The lymphocyte Blastogenesis assay may have potential as a predictive screen to identify contact and photocontact allergens.