The role of interventional radiology in complications associated with liver transplantation.

The evolution of liver transplantation (LT) from an unusual procedure to a practical therapeutic option for patients with life-threatening liver diseases has brought with it several unique challenges. Although the patient survival rates have been steadily improving, with more complex surgeries being performed and increasing duration of graft survival, the overall post LT complication rate continues to stay high. They include inflow complications related to portal vein (PV) or hepatic artery, outflow complications related to hepatic vein or inferior vena cava, biliary leaks or strictures, postoperative collections or abscesses, graft rejection or post-transplant malignancy. These post-transplant complications provide a fertile ground for interventional radiology (IR) to flourish as it can contribute towards the management of each of these, and on most occasions, except for in graft rejection, it can circumvent a major surgery or even re-transplantation. The minimally invasive nature and lower morbidity associated with IR procedures make them preferable to similar surgical procedures. In post-transplant biliary complications, IR and therapeutic endoscopy have almost completely replaced surgery as the first-line treatments. The same can be said regarding the important role that IR plays in the management of most non-acute vascular complications. Meanwhile, more evidence and experience needs to be accumulated in the endovascular treatment of acute vascular complications encountered in the early post-operative period. This review primarily focuses on the various IR strategies in the management of the LT-related vascular and biliary complications with illustrative cases.

Transgenic mice expressing the T cell antigen receptor specific for an immunodominant epitope of a major allergen of house dust mite develop an asthmatic phenotype on exposure of the airways to allergen.

BACKGROUND: Current studies on mechanisms underlying allergen-induced pulmonary inflammation and asthma are hampered by the lack of appropriate physiological in vivo models that reflect the natural route of allergen exposure and sensitization. OBJECTIVE: To generate and phenotype a transgenic mouse strain expressing the T cell receptor (TCR) specific for an immunodominant domain of the major inhalant allergen Dermatophagoides pteronyssinus species of house dust mite (Der p 1), for the development of an in vivo model of allergic asthma. METHODS: Der p 1 transgenic mice were generated using TCR-alphabeta derived from a CD4+ T cell hybridoma reactive with Der p 1 residues p 110-131. The frequency and functional activity of peripheral T cells were determined and parameters of airway inflammation assessed following allergen challenge of the airways with Der p 1. RESULTS: CD4+ T cells are functionally active, exhibiting dose-dependent proliferation and IL-4 production on primary stimulation with Der p 1 or Der p 1, p 110-131 in vitro, independent of in vivo antigen priming. On sensitization of the airways with allergen, in the absence of systemic priming or the application of adjuvants, the TCR transgenic mice develop airway inflammation characterized by a marked lymphocytic and eosinophilic infiltrate with goblet cell hyperplasia and enhanced mucin production. CONCLUSION: The Der p 1 TCR transgenic mice provide a model for investigating the pathophysiological mechanisms of pulmonary inflammation following sensitization by exposure of the airways to allergen and for investigating the mode of action and efficacy of novel immunotherapeutics.

Androgen regulation of stage-dependent cyclin D2 expression in Sertoli cells suggests a role in modulating androgen action on spermatogenesis.

Regulation of spermatogenesis involves stage-dependent androgen action on Sertoli cells, but the pathways involved are unclear. We assessed if cyclin D2 could play a role. In rats, Sertoli cell nuclear, stage-dependent immunoexpression of cyclin D2 switched on after Day 10 and persisted through Day 35, but disappeared by adulthood. However, ethane dimethane sulfonate (EDS)-induced testosterone withdrawal in adult rats for 6 days induced stage-dependent cyclin D2 immunoexpression in Sertoli cells, with highest expression at stages IX-XII and nondetectable at stages VI-VIII (opposite that for androgen receptor [AR] immunoexpression). In EDS-treated rats, a single injection of testosterone but not of estrogen reversed this change in 4 h, and testosterone administration from the time of EDS treatment prevented expression of cyclin D2 in Sertoli cells. The EDS-induced changes in cyclin D2 immunoexpression were matched by changes in expression of Ccnd2 (cyclin D2) mRNA in isolated stage-dissected tubules. Treatment of adult rats with flutamide induced stage-dependent cyclin D2 immunoexpression in Sertoli cells within 18 h, and confocal microscopy revealed that immunoexpression of AR and cyclin D2 were mutually exclusive within individual seminiferous tubules in these animals. Sertoli cell-selective ablation of the AR in mice using Cre/loxP technology also resulted in stage-dependent Sertoli cell cyclin D2 immunoexpression. Downstream from cyclin D2 action is retinoblastoma 1 (RB1), a tumor suppressor protein, immunoexpression of which paralleled stage-dependent AR expression in Sertoli cells; RB1 stage specificity disappeared after EDS treatment. These results point to a non-cell cycle role for cyclin D2 and RB1 in mature Sertoli cells in the stage-dependent mechanisms regulated by AR expression and androgen action.