Unresponsiveness of antidonor cytotoxic T cells in a long-term stable renal transplant recipient.

The antidonor immune response was examined in a one haplotype-mismatched renal transplant recipient with an allograft that had been well-functioning for more than 10 years. Although the relative response of the mixed lymphocyte reaction (MLR) was (45.8)% and the MLR responder cells stimulated by donor cells produced measurable amounts of interleukin-2 (IL-2) (11.6 U/ml), the cytotoxic T lymphocytes (CTL) could not be generated against donor cells, even with exogenous IL-2. These results indicate that antidonor CTL precursors were either deleted or inactivated in this recipient.</p

Analysis of the immune status in the recipients with long-term well-functioning kidneys allografts.

The immune status of thirteen living and related kidney transplant recipients with stable allografts were examined. The immunological assays consisted of a mixed lymphocyte reaction (MLR), cell-mediated lympholysis (CML) assay, interleukin-2 (IL-2) production in mixed lymphocytes culture (MLC) and IL-2 receptor (IL-2 R) expression on MLC cells. The suppression rates of the monoclonal antibodies (mAbs) against IL-2 R were tested on MLRs. The stimulation indices (SI) of the MLR against both donor and third-party cells increased compared with those of pretransplantation. The MLC responder cells stimulated by donor cells produced detectable amounts of IL-2, these amounts were lower than those by third-party cells. The MLC cells against donor cells expressed IL-2 R alpha and beta chains to the same degree as those against third-party cells. Anti-IL-2 R mAbs equally inhibited the MLRs between recipient and donor or third-party cells. Cytotoxic T lymphocytes (CTL) against donor cells were not generated, even with the addition of recombinant IL-2 in any of recipients except one, while anti-donor CTL had been detected prior to transplantation and the CTL against third-party cells were induced in posttranspalnt CML assays. These results indicate that the clonal anergy phenomenon might mediate the specific CTL unresponsiveness observed in kidney transplant recipients and the anergy phenomenon might serve in the long-term acceptance of allograft.</p

Successful pregnancy in renal transplant recipients.

Three cases of successful pregnancies in renal transplant recipients who had undergone transplantation in the Okayama University Medical School Hospital are reported. Two of the women had received an organ from a living relative and one woman received a cadaveric organ graft. These patients, aged 28-37 at the time of the delivery, had received their transplants 2-5 years prior to their conception. The periods of gestation ranged between 35 and 40 weeks. The weight of the babies at birth ranged from 2,380g to 2,500g and the apgar score at 1 min was 8 or 9. None of the infants showed any congenital abnormalities. Lower-segment cesarean section was performed in all of three cases. Serum creatinine levels, an indicator of renal graft function, did not deteriorate during the pregnancy or after delivery. Although further work is needed to solve problems regarding pregnancy in renal transplant recipients, these results encouraged us to meet their hope for a baby.</p

有限要素法を用いた大規模空間吊り天井の脱落被害再現シミュレーション

Many ceiling collapse damages were observed in wide-area structures such as gymnasiums during the 2011 Great East-Japan Earthquake and the 2016 Kumamoto Earthquake. The prevention of ceiling collapse phenomena is an important issue not only to save people\u27s lives, but to keep these facilities to be safely used as shelters after earthquakes. In this paper, a numerical analysis to simulate the ceiling collapse in a full-scale gymnasium specimen, which was tested at the E-Defense shaking table facility in 2014, was conducted. A numerical model consisted of steel structural frames and suspended ceilings were constructed. All the members were modeled using linear Timoshenko beam elements and the adaptively shifted integration (ASI) - Gauss code was applied. Hangers and hanging bolts were modeled in one piece. The plaster boards were assumed as rigid in out of plane direction and only the mass of rock wool boards was considered. Their strength were neglected. Clips and screws were modeled with minute, small elements. Each plaster board was modeled separately to consider local contact between plaster boards, which was simulated by modeling the screws slightly apart. Elasto-plastic buckling of braces and hanging bolts were considered by modeling them with eight beam elements each and two hinge elements on both ends. The clips connecting ceiling joists and ceiling joist receivers are small and delicate components that may be detached during repeated excitation. Once there is a local detachment of clips, a change in the load distribution may cause a chain reaction of detachments, which ends in a drop of plaster boards. Furthermore, the detachments of hanging bolts that are connected to the structural members composing the roof, and failure of screws on plaster boards are assumed to be other main causes of the ceiling collapse. The results of some preliminary tests conducted to see the actual strength of these components are implemented in the analysis for criteria. The numerical result was validated by the experimental result, which was performed at the E-Defense under an input of two continuous K-NET Sendai 50% waves. The acceleration responses, the spectrum and the displacement responses obtained on the roof matched well with the experimental result. According to the results, the plaster boards near walls pattered down occasionally at the first peak of the first wave. These were due to detachment of clips and screws caused by collisions to the walls. Then, the clips near roof top began to get loose due to buckling of hanging bolts caused by vertical excitation, which ends, at the first peak of the second wave, in drop of plaster boards in a wide range. The numerical result had shown the collapse of the ceilings progressed owing to the detachment of clips that connected the ceiling joists to the ceiling joist receivers, which eventually led to a large-scale collapse of the ceilings

The impact of triple drug immunosuppression on clinical results of cadaveric kidney transplantation: a comparison of conventional immunosuppression.

A retrospective study was carried out in 110 cadaveric kidney transplant recipients to compare the effects of low doses of cyclosporine (CsA), azathioprine (AZP) and steroids (triple-drug therapy) with those of higher doses of steroids plus AZP (conventional immunosuppression). Graft survival rate in the triple-drug therapy was 77%, 69%, and 69% at 1, 3, and 5 years, respectively. This was significantly better than 48%, 34%, and 29% in conventional immunosuppression. The incidence of acute rejection episodes was significantly lower in the triple-drug therapy than in conventional immunosuppression (25% vs 58%). In conclusion, our study shows that triple-drug therapy using low-dose cyclosporine is the safest of the immunosuppressive regimens and provides a beneficial effect on the long-term survival of cadaveric kidney transplants.</p

Renal transplantation from HLA-haploidentical living-related donors: the effects of donor-specific blood transfusions and different immunosuppressive regimens.

One-hundred-nine HLA-haploidentical living related renal transplants have been retrospectively analysed to compare the effect of donor-specific blood transfusion (DST) and different immunosuppressive regimens on graft survival and acute rejection. The recipients were divided into four groups according to the immunosuppressive therapy. Group 1 (n = 44): conventional therapy with posttransplant azathioprine (AZP) + methylprednisolone (MP). Group 2 (n = 25): pretransplant DST + posttransplant AZP + MP. Group 3 (n = 12): triple-drug therapy with posttransplant AZP + MP + cyclosporine (CS). Group 4 (n = 25): pretransplant DST + posttransplant AZP + MP + CS. The five-year actuarial survival rates for groups 1, 2, 3 and 4 were 48%, 73%, 79%, and 89%, respectively. The graft survival rate in group 3 was significantly (p less than 0.01) better than that in group 1. The transfusion effect was reduced, and appears as a 10% improvement in the graft survival in the cyclosporin era compared with a 25% improvement at pre-cyclosporin era. Furthermore, the incidence of the first rejection episode was decreased in recipients that received DST. The present study revealed that DST, as pretransplant conditioning has a definite impact on rejection-free long-term graft survival in HLA-haploidentical living-related kidney recipients and the most favorable outcome in such patients could be achieved by DST pretreatment in conjunction with posttransplant triple-drug therapy including cyclosporine.</p

Two-step parameter identification of multi-axial cyclic constitutive law of structural steels from cyclic structural responses

This paper presents a two-step Bayesian optimization (BO) method for identifying the elastoplastic material parameters of structural steels subjected to multi-axial cyclic loading. A series of simple elastic and elastoplastic shaking table tests is conducted for a structure that has a steel specimen experiencing elastoplastic response. An inverse problem is formulated to identify the multi-axial material parameters of the specimen from the structural responses obtained by the shaking table tests. This is notable because it is more difficult to carry out multi-axial static cyclic material tests than to conduct dynamic cyclic structural tests. The inverse problem minimizes the error between the measured structural responses and those simulated by finite element (FE) analysis. The two-step BO devised for solving the inverse problem successfully offers a global optimization framework while considerably reducing the number of costly simulations. It first seeks to infer Young’s modulus values from the cyclic elastic responses of the structure, thereby validating the FE model in its elastic state. It then finds the parameters for the nonlinear combined isotropic/kinematic hardening model of the specimen using the cyclic elastoplastic responses of the structure. Verification results show that the parameters identified by the proposed method well reproduce the cyclic responses of the structure under different cyclic loading conditions

Utility of Maternal 6-Thioguanine Nucleotide Levels in Predicting Neonatal Pancytopenia

Abstract An infant with pancytopenia was born to a mother who used the common immunosuppressant azathioprine (AZA). Maternal and neonatal blood levels of 6-thioguanine nucleotides (6TGN; metabolite of AZA) were 1890 and 1480 pmol/8 × 108 red blood cells, respectively. Maternal 6TGN levels could be useful in predicting neonatal pancytopenia