Theophylline-bearing microspheres with dual features as a coordinative adsorbent and catalytic support for palladium ions

Polystyrenic microspheres in the sub 5 micrometer size range (micro-gel) with –CH₂Cl active sites were synthesized via the dispersion polymerization of 4-chloromethylstyrene, divinyl benzene and methoxy polyethylene glycol acrylate. Then, theophylline residues were introduced onto the polystyrenic microspheres via the substitution of the chloride in the –CH₂Cl group to prepare chelate type microspheres of μ-T2. It was found that the microspheres have co-continuous structures, monodispersed particle sizes, and excellent solvent and water wettability. Using the μ-T2 microspheres possessing theophylline residues, adsorption experiments involving the adsorption of palladium(ii), copper(ii) and platinum(iv) from acidic chloride media under both individual and mixed conditions were carried out and it was found that the μ-T2 microspheres exhibited excellent adsorption selectivity for palladium(ii) over copper(ii) and platinum(iv). It was also revealed that thiourea or ammonia solutions are the most effective in desorbing palladium ions from the microspheres. Despite being used in four adsorption–desorption cycles, the μ-T2 microspheres were still able to strongly adsorb palladium ions, with an adsorption of over 85%. In addition, the μ-T2 microspheres also showed palladium capturing ability even in very dilute palladium solutions (below 1.0 ppm). Interestingly, the μ-T2 microsphere-adsorbed palladium ions exhibited excellent catalytic activity in the Suzuki–Miyaura coupling reaction of bromobenzene and phenylboronic acid, yielding biphenyl in 100% under the conditions within 1 hour at 50 °C in water.

Sub 5 micrometer sized polystyrenic microspheres bearing theophylline residues were synthesized and used as adsorbent and catalytic support for palladium ions.     

High-dose 131I-metaiodobenzylguanidine therapy in patients with high-risk neuroblastoma in Japan

Annals of Nuclear Medicine - The aim of the study was to investigate the outcomes and prognostic factors of high-dose 131I-metaiodobenzylguanidine (131I-MIBG) therapy in patients with refractory or...     

Protective effects of simultaneous splenectomy on small‐for‐size liver graft injury in rat liver transplantation

Splenectomy is an effective technique in living donor liver transplantation (LDLT) with small‐for‐size (SFS) liver grafts for overcoming SFS liver graft injury. However, the protective mechanism of splenectomy is still unclear. The aim of this study was to investigate how splenectomy could attenuate SFS graft injury through the measurement of biochemical factors, particularly the expression of endothelin (ET)‐1, which is a key molecule of microcirculatory disorders by mediating sinusoidal vasoconstriction. We performed rat orthotopic liver transplantation using SFS liver grafts with or without splenectomy. We investigated intragraft expression of ET‐1 mRNA and hepatic protein levels of ET‐1. In addition, portal pressure, hepatic injury and morphological changes, and survival rate were evaluated. In result, intragraft ET‐1 mRNA expression after SFS liver transplantation was significantly downregulated by splenectomy, and hepatic expression of ET‐1 in SFS grafts was rarely observed. Splenectomy inhibited the increase in portal pressure, ameliorated SFS liver graft injury and improved the graft survival rate after SFS liver transplantation. In conclusion, splenectomy improved the SFS liver injury and decreased the expression of ET‐1 by attenuating portal hypertension on SFS liver transplantation. Downregulation of intragraft ET‐1 expression plays important roles in the protective mechanism of splenectomy in SFS liver transplantation.     

Selective expansion of donor‐derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome

IPEX syndrome is a rare and fatal disorder caused by absence of regulatory T cells (Tregs) due to congenital mutations in the Forkhead box protein 3 gene. Here, we report a patient with IPEX syndrome treated with RIC followed by allogeneic BMT from an HLA‐matched sibling donor. We could achieve engraftment and regimen‐related toxicity was well tolerated. Although the patient was in mixed chimera and the ratio of donor cells in whole peripheral blood remained relatively low, selective and sustained expansion of Tregs determined as CD4+CD25+Foxp3+ cells was observed. Improvement in clinical symptoms was correlated with expansion of donor‐derived Tregs and disappearance of anti‐villin autoantibody, which was involved in the pathogenesis of gastrointestinal symptoms in IPEX syndrome. This clinical observation suggests that donor‐derived Tregs have selective growth advantage in patients with IPEX syndrome even in mixed chimera after allogeneic BMT and contribute to the control of clinical symptoms caused by the defect of Tregs.     

Left Ventricular Mass Regression After Implantation of St. Jude Medical Cardiac Valves in Small Aortic Roots

In this study, we analyzed the extent of regression of left ventricular hypertrophy in patients who received small St. Jude Medical (SJM) aortic valves and compared the results with those of another group receiving larger valves. Eighty-eight patients received either 19 or 21 mm valves (Group 1, 25 patients) or either 23 or 25 mm valves (Group 2, 53 patients). Echocardiographic studies were done before the operation and 5 years postoperatively. At follow-up a significant reduction in the left ventricular mass was found for both patient groups (p < 0.0001). Doppler echocardiography derived pressure gradients for both groups were obtained during the follow-up period. As expected, the patients in Group 1 had higher peak pressure gradients than did those in Group 2. However, there was no significant difference between the 2 groups or any significant correlations between peak pressure gradients and body surface area (BSA). Actuarial survival was 84.7% at 15 years for Group 1 and 85.9% at 17 years for Group 2. Actuarial freedom from valve related events was 91.4 % at 15 years for Group 1 and 82.7% at 17 years for Group 2. There was no significant difference in survival or valve related event free curves between the 2 groups. After implantations of SJM valves in small aortic roots, significant left ventricular mass regression was obtained, and the results were comparable to those for valves of other sizes. The long-term performance of aortic valve replacement with small valves was satisfactory as judged by improvement in the functional class of patients and survival statistics, the durability of the prosthesis, and valve related morbidity comparable to that of valves of other sizes.     

Therapeutic effect of alpha-galactosylceramide-loaded dendritic cells genetically engineered to express SLC/CCL21 along with tumor antigen against peritoneally disseminated tumor cells

The close cooperation of both innate and acquired immunity is essential for the induction of truly effective antitumor immunity. We tested a strategy to enhance the cross-talk between NKT cells and conventional antigen-specific T cells with the use of alpha GalCer-loaded dendritic cells genetically engineered to express antigen plus chemokine, attracting both conventional T cells and NKT cells. DC genetically engineered to express a model antigen, OVA, along with SLC/CCL21 or monokine induced by IFN-gamma/CXCL9, had been generated using a method based on in vitro differentiation of DC from mouse ES cells. The ES-DC were loaded with alpha-GalCer and transferred to mice bearing MO4, an OVA-expressing melanoma, and their capacity to evoke antitumor immunity was evaluated. In vivo transfer of either OVA-expressing ES-DC, stimulating OVA-reactive T cells, or alpha-GalCer-loaded non-transfectant ES-DC, stimulating NKT cells, elicited a significant but limited degree of protection against the i.p. disseminated MO4. A more potent antitumor effect was observed when alpha-GalCer was loaded to ES-DC expressing OVA before in vivo transfer, and the effect was abrogated by the administration of anti-CD8, anti-NK1.1 or anti-asialo GM1 antibody. alpha-GalCer-loaded double transfectant ES-DC expressing SLC along with OVA induced the most potent antitumor immunity. Thus, alpha-GalCer-loaded ES-DC expressing tumor-associated antigen along with SLC can stimulate multiple subsets of effector cells to induce a potent therapeutic effect against peritoneally disseminated tumor cells. The present study suggests a novel way to use alpha-GalCer in immunotherapy for peritoneally