Intragraft gene expression profile associated with the induction of tolerance by allochimeric MHC I in the rat heart transplantation model.

The MHC class I allochimeric protein containing donor-type epitopes on recipient-type heavy chains induces indefinite survival of heterotopic cardiac allografts in rats. We analyzed gene expression profile of heart allograft tissue. Mutated peptide [alpha1h1/u]-RT1.Aa that contains donor-type (Wistar Furth, WF; RT1u) immunogenic epitopes displayed on recipient-type (ACI, RT1a) was delivered into ACI recipients of WF hearts at the time of transplantation in addition to a 3 days course of oral cyclosporine. Microarray analysis was performed using Affymetrix Rat 230 2.0 Microarray. Allochimeric molecule treatment caused upregulation of genes involved in structural integrity of heart muscle, downregulation of IL-1beta a key modulator of the immune response, and downregulation of partitioning defective six homolog gamma PAR6, which is involved in T cell polarity, motility, and ability to scan dendritic cells (DC). These indicate that the immunosuppressive function of allochimeric molecule and/or the establishment of allograft tolerance depend on the induction of genes responsible for the heart tissue integrity, the suppression of cytokine pathway(s), and possibly the impairment of T cells mobility and their DC scanning ability. These novel findings may have important clinical implications for inhibition of chronic rejection in transplant recipients.

The biopsy-proven benign thyroid nodule: is long-term follow-up necessary?

BACKGROUND: Thyroid nodules are common, and of those biopsied by fine-needle aspiration (FNA), the majority will be benign colloid nodules (BCN). Current guidelines suggest these BCN should be followed by ultrasonographic examination (US) every 3 years, with no endpoint specified. This study evaluated if long-term follow-up of benign thyroid nodules was associated with change in treatment or improvement in diagnosing a missed malignancy compared with short-term follow-up. STUDY DESIGN: All patients with FNA-based diagnosis of BCN at our institution from 1998 to 2009 were identified. Patients observed after the diagnosis were divided into short-term follow-up (<3 years) and long-term follow-up (≥3 years). Rates of repeat FNA, thyroidectomy, and malignancy detection were compared. RESULTS: Of 738 patients with BCN, 92 patients underwent thyroid resection after the initial US. Six hundred forty-six patients were observed, of which 366 returned for 1 or more follow-up US: 226 in the short-term group (median 13 months) and 140 in the long-term group (median 57 months). There were more follow-up US in long-term vs short-term (medians 4 vs 2, p < 0.01), more repeat FNAs in the long-term group (18 of 140 vs 8 of 226, p < 0.01); but no difference in interval thyroidectomies (13 of 140 vs 31 of 226, p = 0.25) or malignant final pathology (0 of 13 vs 2 of 31, p > 0.99). For all patients undergoing surgery, pathology was malignant in 2 of 136 (1.5%). CONCLUSIONS: Long-term follow-up of patients with BCN is associated with increased repeat FNA and US without improvement in the malignancy detection rate. After 3 years of follow-up, consideration should be given to ceasing long-term routine follow-up of biopsy-proven BCN.