Enantioselective Alkylation of Hydrophobic Vitamin B12 Bearing a Binaphthyl Moiety

The enantioselective alkylation of hydrophobia vitamin B12 derivatives at the β-axial site was examined in methanol with various alkyl bromides, and those B12 analogues bearing a peripheral binaphthyl moiety showed the highest S-selectivity toward enantiomeric alkyl bromides among vitamin B12 models as caused by a steric effect of the peripheral substituent

Photolysis of Hydrophobic Vitamin B12 Derivatives Covalently Bound to Lipid in Aqueous Media

An alkyl ligand coordinated to hydrophobic vitamin B12 derivatives covalently bound to N,N-dihexadecyl-Nα-[6-(trimethylammonio)hexanoyl]-L-aspartamide bromide underwent a novel bromination reaction along with its rearrangement in the single-walled vesicle of N,N-dihexadecyl-Nα-[6-(trimethylammonio)hexanoyl]-L-alaninamide bromide under photolysis conditions

Role of a 65-kDa Heat Shock Protein in Protective Immunity against Toxoplasma Infection

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Development of malaria vaccines that block transmission of parasites by mosquito vectors

Malaria is still one of the infectious diseases urgently requiring control and causes socioeconomic burdens on people residing in developing countries. Malaria vaccines are expected to control the disease. However, there is no effective vaccine available despite the intense efforts of malaria scientists. One strategy for a malaria vaccine is to prevent parasite spread by means of interfering with parasite development in mosquito vectors, which is the so-called transmission-blocking vaccine (TBV). We will here review the current progress of TBV

ナゼ アレルギー シッカン ワ ゾウカ シテ イルノカ : メンエキガク ノ タチバ ヨリ

Type I allergic diseases, such as rhinitis, pollinosis and bronchial asthma, are mediated by Th2-type helper T cell induction, specific IgE antibody production and mast cell activation. Increases of these allergic diseases in recent years might be caused by skewed differentiation of T cells toward Th2 cells by some environmental factors including diesel exhaust particles and decreases of virus and bacteria infection in childhood. The decrease of parasite infection is also thought to affect the susceptibility against allergic diseases by eliciting polyclonal IgE production that suppresses mast cell activation. Important clues for prevention and therapy of the allergic diseases would be derived from further investigations of the relationship between the diseases and these environmental factors

Expression of 65 000 MW Heat-shock Protein in SCID Mice Infected with Toxoplasma gondii after Transplantation of Mouse Fetal Thymus

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Experimental study of combined treatment with tacrolimus and donor splenocytes via the portal vein in small bowel transplantation

We previously reported that the combined treatment of perioperative administration of donor splenocytes via the recipient's portal vein (DSPV) and a short-course Tacrolimus significantly prolonged the survival of fully allogenic grafts in rat small bowel transplantation (SBTX). In the present study we examined whether this effect depended on the quantity of the administered alloantigens in DSPV. In addition, we examined the expression of the surface antigen on T cells of the splenocytes and the induced toleragenic factor, according to the tolerant recipients which in our previous report had shown the prolongation of allogenic transplant small bowel graft survival by the combined treatment of DSPV (1×108 donor splenocytes) and a short-course Tacrolimus. Donor splenocytes were prepared from Brown-Norway (BN (RT1n)) rat spleens for Lewis (LEW (RT1l)) recipients. The recipients (n=10), treated with a short course of Tacrolimus (0.5mg/kg, 0 to 3 days postoperatively) only showed graft rejection with an average of 6.3±1.0 days postoperatively. However, the combined treatment, consisting of DSPV of 1×108 donor splenocytes and a short course Tacrolimus significantly prolonged graft survival to 12.7±2.1 days (n=12, P<0.01). DSPV of less than 1×108 donor splenocytes (5×107 cells and 2.5×107) could not prolong the graft or animal survival under a short-course Tacrolimus treatment. In the tolerant recipients, the CD4 and CD8 percentages of splenocytes were not significantly different from those of control rats or recipients that were treated with short-course Tacrolimus alone. Neverthless, the percentage of Tcr-αβ+ cells expressing IL-2 receptor (R) was significantly lower than in either control rats or the recipients with short-course Tacrolimus. In the suppression assay to one-way mixed lymphocyte response, a toleragenic factor was suggested to the present in the serum of the tolerant recipients. In the present study, it was suggested that the effects of the combined treatment of DSPV and short-course Tacrolimus for the prolongation of graft survival in the rat allogenic SBTX should depended on the quantity of the antigens administered into the portal vein. The beneficial effects of this treatment were reflected in the suppression of IL-2R on the recipient's splenocytes, and tolerogenic factor(s) might subsequently be induced in the tolerant recipient's serum

Humoral and cell-mediated immunity to MSP3 peptides in adults immunized with MSP3 in malaria endemic area, Burkina Faso

We performed a single-blind, randomized phase 1 trial of the long synthetic peptide (LSP) of merozoite surface protein-3 (MSP3) in adults living in Burkina Faso. Thirty eligible volunteers were randomized to receive either the MSP3-LSP candidate vaccine or tetanus toxoid vaccine as a control. A dose of each vaccine was administered on days 0, 28 and 112 and the vaccine was formulated with aluminium hydroxide. Humoral immune responses were assessed by ELISA at days 0, 28, 56, 112, 140, 252 and 365 and cell-mediated immune responses by lymphoproliferation assay and by ELISA on days 0, 56 and 140. IgG responses to four peptides of MSP3 were similar in both vaccine groups. Higher IgG concentrations were recorded after the beginning of malaria high transmission season in both vaccine groups. The lymphocyte proliferation and the production of IFN-γ in response to stimulation with the four overlapping peptides increased following vaccination in the MSP3-LSP vaccine group, but did not change appreciably in the control group. In contrast to natural infection, MSP3-LSP did not boost humoral responses to the four overlapping peptides of MSP3 to any detectable degree in our semi-immune adult. MSP3-LSP may be more immunogenic in young children with little or no acquired immunity

Hydrophobic Vitamin B12. XI. Preparation, Characterization, and Enantioselective Alkylation of Hydrophobic Vitamin B12 Bearing a Binaphthyl Moiety

Hydrophobic vitamin B12 derivatives bearing a chiral binaphthyl moiety, hexamethyl 71-decarboxy-71-[(R)-2′-methoxy-1,1′-binaphthyl-2-carboxymethyl]cobyrinate perchlorate [B12–BINAP(R)] and hexamethyl 71-decarboxy-71-[(S)-2′-methoxy-1,1′-binaphtyl-2-carboxymethyl]cobyrinate perchlorate [B12–BINAP(S)], were prepared from cyanocobalamin. These complexes were characterized by means of electronic and circular dichroism spectroscopy as well as by cyclic voltammetry in comparison with those data for a hydrophobic vitamin B12 without a binaphthyl moiety. The enantioselective alkylation of hydrophobic vitamin B12 derivatives at the β-axial site was examined in methanol with various 3-bromo-2-methylpropionic esters by means of 1H NMR spectroscopy. All the hydrophobic vitamin B12 derivatives used here, the one bearing methoxycarbonyl groups as peripheral substituents without a binaphthyl moiety, B12–BINAP(R), and B12-BINAP(S), were found to bind (S)-2-methylpropionates more favorably than the corresponding R-enantiomers; the highest S-selectivity was observed with the latter two derivatives, 65% e.e. The cause of such S-enantioselectivity was discussed with attention to stereochemical configurations of the peripheral substituents placed in the corrin ring

Role of innate immune cells in protection against Toxoplasma gondii at inflamed site

The intraperitoneal infection with Toxoplasma gondii (T. gondii) caused accumulation of γδ T, NK, NK1.1+T-like (NKT) cells at inflamed sites. To clarify the roles of these cells in protection against T. gondii at the inflamed sites, BALB/c mice were depleted of γδ T, NK, NK and NKT cells by treatment with antibody against TCR-γδ, asialoGM1 or Interleukin-2 receptor β-chain (IL-2Rβ), respectively, prior to infection. Mice treated with anti-TCR-γδ monoclonal antibody (mAb) became more susceptible to infection, whereas mice treated with anti-IL-2Rβ mAb acquired resistance. Treatment with anti-asialoGM1 Ab showed no effect. We previously reported that heat shock protein 65 (HSP65) in macrophages induced by γδ T cells plays an essential role in protective immunity against T. gondii infection, by preventing apoptotic death of infected macrophages. In the present study, we showed that treatment with anti-IL-2Rβ mAb, but not with anti-asialoGM1 Ab, enhanced the HSP65 induction in macrophages, and inhibited Interleukin-4 (IL-4) expression in nonadherent peritoneal exudate cells. Furthermore, neutralization of endogenous IL-4 by anti-IL-4 mAb enhanced the HSP65 induction in macrophages. These findings suggest that NKT cells, but not NK cells, negatively regulate the protective immunity against T. gondii infection possibly by producing IL-4and suppressing HSP65 induction