Contents Volume 32 No. 1 (2000) Section One: International Urology and Nephrology

Table of Contents

Contents Volume 32 No. 1 (2000) Section One: International Urology and Nephrology     

Major histocompatibility complex class I peptide-pulsed host dendritic cells induce antigen-specific acquired thymic tolerance to islet cells

BACKGROUND: As T-cell receptor-major histocompatibility complex (MHC) class I/self peptide interaction regulates T-cell development in the thymus, we reasoned that presentation of peptides by self dendritic cells (DC) to developing T cells in the thymus might induce acquired thymic tolerance. This hypothesis is based on the finding that intrathymic injection of allopeptides in the adult animal induces acquired tolerance. To examine this hypothesis, we studied the effects of intrathymic (IT) injection of a single immunodominant Wistar-Furth (WF) MHC class I (RT1.Au) peptide-pulsed host DC on islet allograft survival in the WF-to-ACI rat combination. METHODS: Bone marrow-derived ACI DC expressing MHC class I and II, OX62, and ED2 present allopeptides to naive and specifically peptide-primed syngeneic T cells in mixed lymphocyte reaction. Host DC pulsed with RT1.Au peptide 5 (residues 93-109) were injected into the thymus of streptozotocin-induced diabetic ACI that were transplanted 7 days later with donor-type (WF) or third-party (Brown Norway [BN]) islets. RESULTS: Whereas IT injection of 300 microg of peptide 5 alone led to normoglycemia and permanent islet survival in three of six diabetic ACI recipients, similar treatment combined with simultaneous intraperitoneal injection of 0.5 ml of anti-lymphocyte serum (ALS) on day -7 led to 100% permanent islet allograft survival (>200 days) compared to a mean survival time of 15.0+/-2.3 days in controls treated with ALS alone. In contrast, similarly prepared animals rejected the third-party (BN) islets in an acute fashion. To address the question of indirect allorecognition in acquired thymic tolerance, we examined the effect of peptide-pulsed host DC on graft survival. Whereas IT injection of peptide-pulsed host DC alone resulted in permanent islet survival in two of five animals, IT injection of peptide-pulsed host DC combined with 0.5 ml of ALS induced 100% donor-specific permanent islet allograft survival in the WF-to-ACI rat combination. These results suggest that thymic DC take up, process, and present the administered peptide to the developing T cells by the indirect allorecognition pathway in the induction of acquired thymic tolerance. CONCLUSION: We have demonstrated a novel approach to inducing transplant tolerance to islet allografts with IT injection of allopeptide-pulsed host DC. This finding suggests that immunization strategies using DC expressing MHC allopeptides or peptide analogue might be potentially useful in the treatment of autoimmune diabetes mellitus.     

Early posttransplant lymphoproliferative disorder presenting with ureteric obstruction in en bloc kidneys

We describe a female patient who received double pediatric (en bloc) kidney transplants. She presented initially with fever of unknown origin 3 months after transplantation; 5 months after surgery, she presented with obstruction of one ureter followed by obstruction of the other. After 9 months she developed posttransplant lymphoproliferative disorder in both kidneys. To our knowledge, this is the first case report of this disorder occurring in en bloc kidneys and presenting with bilateral ureteric obstruction.     

Sub-acute sensory neuronopathy as a preceding sign of recurrence in colon carcinoma

Subacute sensory neuronopathy is a paraneoplastic syndrome, which occurs mostly in lung, breast, ovarian malignancies and lymphoma. A 75-yr-old woman who was at the twentieth month of her postoperative follow-up owing to colon adenocarcinoma admitted with subacute sensory neuronopathy. Six months later from the first, neuropathic symptoms liver metastases developed. To the best of our literature review subacute sensory neuronopathy as a preceding sign of recurrence in colon adenocarcinoma has not previously been reported. We conclude that, in the case of subacute sensory neuronopathy without an obvious underlying etiological factor, an occult malignity should always be researched in clinical practice.     

Acute bronchodilatory effect of salmeterol on methacholine-induced bronchoconstriction in childhood asthma

Abstract A review of the literature highlights the need for research, particularly on the acute bronchodilatory effect of salmeterol on bronchoconstriction in the pediatric age group. The present study attempted to evaluate the acute bronchodilatory effect of salmeterol on methacholine-induced bronchoconstriction in childhood asthma and to compare it with the effect of salbutamol. Forty-four asymptomatic children with mild-to-moderate asthma (23 boys and 21 girls; aged7–17 years) were studied. At the beginning, the baseline forced expiratory volume in 1 s (FEV₁) was measured, and the methacholine challenge was performed by doubling the dose to determine PC₂₀ (provocative concentration of inhaled methacholine required to reduce FEV! by 20%). At the same time, the transcutaneous arterial oxygen saturation (S_ao₂) was also measured. Each subject inhaled a single dose of 25 μ salmeterol (n: 23, group I) or 100 μg salbutamol (n: 21, group II) following the Sp₂ measurement. The same measurements (FEV₁, S_ao₂) were repeated 5 and 20 min after the inhalation. After inhalation of salmeterol or salbutamol, the differences between the values of FEV₁ and S_aO₂ after 5 and 20 min were insignificant in both group I and group II (P > 0.05), although there was a significant improvement in both FEV₁ and S_aO₂ after 5 and 20 min (P < 0.005). From these findings it was concluded that salmeterol can be considered as effective as salbutamol on methacholine-induced bronchoconstriction.