岩見 大基

Background. The effects of histamine on immunologic responses via the histamine receptor 2 (HR2) have been studied, but few investigations explored the immunomodulatory role of histamine in vivo. We examined whether the HR2 antagonist ranitidine affects the alloimmune response in a murine model of cardiac transplantation. Methods. CBA (H-2(k)) recipients were given no treatment or one intravenous injection of ranitidine on the day of transplantation of a heart from C57BL/10 (H-2(b)) donors. Survival of the allografts was recorded. The effect of the ranitidine treatment on cell proliferation and cytokine production was assessed by mixed leukocyte culture and enzyme-linked immunosorbent assays. An adoptive transfer study was conducted to determine whether regulatory cells were generated. The effect on graft survival of adding FK506 to the ranitidine treatment was also examined. Results. CBA recipients given ranitidine (60 mg/kg) had prolonged graft survival (median survival time [MST], 87 days). Ranitidine treatment also suppressed the proliferation of splenocytes and production of interleukin (IL)-2 and up-regulated IL-10 production. Adoptive transfer of splenocytes and CD4(+) cells from ranitidine-treated allograft recipients induced significant prolongation of allograft survival in naive secondary recipients (MST, 71 and > 100 days, respectively). CBA recipients given both ranitidine and FK506 (0.1 mg/kg/day for 14 days) had indefinite survival of cardiac allografts (MST, > 100 days). CBA recipients treated with FK506 alone rejected the allografts (MST, 27 days). Conclusion. In our model, ranitidine treatment induced significantly prolonged survival of fully allogeneic cardiac grafts, generated CD4(+) regulatory cells, and indefinite survival when combined with FK506 (0.1 mg/kg/day).

Suppression of antibody-mediated rejection (AMR) is mandatory for the acceptance of renal allograft in ABO blood type incompatible and pre-sensitized combinations. The aim of this study was to evaluate the difference in histopathology of AMR between ABO incompatible (ABOI) and pre-sensitized cases. Among 69 kidney recipients who underwent transplant surgery at our institute since 2002, four patients who manifested AMR were included in this study. They initially received quadrant immunosuppressants, tacrolimus, mycophenolate mofetil, methylprednisolone and basiliximab. Two patients received grafts from ABOI donors and the other two received grafts from flow T-cell crossmatch-positive donors. Although satisfying antibody removal was achieved by pre-transplant plasmapheresis, all four cases manifested acute AMR, within two wk post-transplant. Antibody titer and panel reactive antibody increased at the time of AMR. ABOI cases showed slight cellular infiltration. These cases showed diffuse, strong and linear deposition of C4d at peritubular capillaries (PTC). On the other hand, pre-sensitized cases showed more intense cellular infiltration, especially in glomerulus but only faint and focal deposition of C4d at PTC. All four cases were treated with corticosteroid pulse therapy in conjunction with several sessions of plasmapheresis.

INTRODUCTION: Recent immunosuppression with tacrolimus and mycophenolate mofetil has improved the results of renal transplantation. In this study, we analyzed the effect and safety of basiliximab as an induction therapy. MATERIAL AND METHODS: Forty-nine kidney recipients were given tacrolimus, mycophenolate mofetil and prednisone (non-Bas group), and 31 recipients were given basiliximab as an induction therapy in addition to the triple immunosuppressants (Bas group). Graft function, incidence of acute rejection (AR), findings of protocol graft biopsy and adverse effects were compared. RESULTS: Serum creatinine within 1 yr post-transplant was comparable between the two groups. Incidence of biopsy-proven AR within 6 months post-transplant was less in the Bas group than in the non-Bas group. Borderline change at 3 months post-transplant was less in the Bas group when compared to the non-Bas group. The frequency and severity of tubulitis were higher in the non-Bas group than in the Bas group. The addition of basiliximab did not increase opportunistic infection, but reduced tacrolimus nephrotoxicity. CONCLUSION: The addition of basiliximab to the tacrolimus-based triple immunosuppressive regimen enabled us to reduce the doses of immunosuppressants and tacrolimus nephrotoxicity without increasing early rejection or infection. This regimen is safe and effective for application during the early period after renal transplantation.

We report on a case of a pure urogenital sinus anomaly presented with bladder distention. A seven-day-old girl with an abdominal distension was referred to the Division of Urology, Hakodate Central Hospital, Hakodate, Japan. A common urogenital sinus without abnormalities in the labium, clitoris or anus was found. A computed tomography (CT) scan documented a distended bladder without hydrometrocolpos or hydroureteronephrosis. Cystography performed at 44 days revealed a large flaccid bladder without ureteral reflux. Urinary management by an indwelling urethral catheter was maintained until 3 months, when an endoscopic examination was performed and a stenotic urethral-type urogenital sinus with low confluence was diagnosed. Parents successfully instituted clean intermittent catheterization as a temporary urinary management, and postvoid residual urine gradually decreased. At 2 years of age, flap vaginoplasty was performed. In an urodynamic study performed postoperatively, the detrusor pressure during voiding was 40-50 cm H2O. The patient maintained spontaneous voiding without consequences. Appropriate urinary care is essential to prevent urological complications in cases with a pure urogenital sinus anomaly.