Altered expression of MHC isoforms is a sensitive indicator in the diagnosis of acute and chronic cardiac rejection. The pathophysiology of this alteration in MHC isoform expression should be studied further to elucidate the pathogenesis of cardiac rejection.

Abstract-Cardiac allograft arteriopathy, which limits the long-term survival of recipients, is characterized by diffuse intimal thickening composed of proliferative smooth muscle cells. The transcription factor E2F plays a pivotal role in the coordinated transcription of cell-cycle regulatory genes. To test the hypothesis that double-stranded DNA with specific affinity for E2F (E2F decoy) is effective in preventing intimal hyperplasia, we performed ex vivo single intraluminal delivery of E2F decoy into cardiac allografts of mice and Japanese monkeys using the hemagglutinating virus of Japan (HVJ) artificial viral envelope-liposome method. In murine models, antisense cyclin-dependent kinase 2 (cdk2) kinase oligodeoxynucleotide (ODN) and no transfers were performed to compare the effects. Severe intimal thickening was observed, and multiple cell-cycle regulatory genes were enhanced in untreated allografts. E2F decoy prevented neointimal formation and suppressed these genes for up to 8 weeks, whereas antisense cdk2 kinase ODN had limited effects. In primate models, E2F decoy dramatically prevented neointimal thickening and suppressed multiple cell-cycle regulatory genes, whereas intimal thickening developed in the nontransfected or mismatch decoy-transfected allografts. Gel mobility shift assay proved the specific effects of E2F decoy, and reverse transcriptase-polymerase chain reaction documented that neither complication nor dissemination of HVJ into other organs was observed. We demonstrate that ex vivo gene delivery to allografts is a potent strategy to modify allograft gene expression, resulting in prevention of graft arteriopathy without systemic adverse effects. Key Words: primate Ⅲ heart transplantation Ⅲ transcription factor Ⅲ arteriosclerosis Ⅲ gene therapy C ardiac transplantation often results in accelerated graft coronary disease in long-term survivors. 1 Neointimal hyperplasia of the coronary arteries results from vascular smooth muscle cell (SMC) proliferation; this proliferation is dependent on the coordinated actions of cell-cycle regulatory genes. 2 Recently, we reported that antisense cyclin-dependent kinase (cdk) 2 kinase oligodeoxynucleotide (ODN) prevents neointimal formation in murine cardiac allografts. 3 The transcription factor E2F regulates multiple cell-cycle regulatory genes, which are critical to the process of cell growth and proliferation. 4,5 Double-stranded DNA with high affinity for E2F acting as a decoy (E2F decoy) inhibits cell-cycle regulatory gene expression and SMC proliferation in rat carotid injury models. 6 However, the effect of E2F decoy in preventing graft coronary arterial neointimal formation has not been investigated. Several gene therapy trials have been performed in search of methods to prevent and treat several diseases using the hemagglutinating virus of Japan (HVJ)-liposome method. 7 Recently, HVJ artificial viral envelope (AVE) liposome, which is a modified method of HVJliposome delivery, has been demonstrated to increase efficiency of cellular uptake of ODN. 8...

No abstract

SUMMARYAtrial septal defect (ASD) is the most common congenital heart anomaly encountered in adults. For patients over 60 years old, acceptable operative mortality and symptomatic improvement following surgery have been reported. We reviewed patients with ASD aged over 70 years and studied their preoperative hemodynamics, the surgical procedures used and the results.Between January 1994 and December 1996, 18 patients over the age of 40 years underwent surgical repair of ASD. Four patients were over 70 years of age (Group A). The other 14 patients were studied as a control group (Group B). We compared the preoperative clinical status, hemodynamic data, and surgical results between the two groups. The postoperative clinical status of Group A was studied during the follow-up period.The NYHA functional class of the elderly patients was greater than that of the middle-aged patients. None of the elderly patients had pulmonary hypertension. Moderate or severe tricuspid valve regurgitation (TR) due to annular dilatation was found, and tricuspid annuloplasty was performed in all four elderly patients. There were no operative or hospital deaths in either group. The NYHA functional class and TR improved in all the aged patients after surgery.In order to prevent progressive tricuspid annular dilatation due to an intraatrial left to right shunt, surgical closure of ASD should be performed for physically active adult patients. (Jpn Heart J 1997; 38: 677-684)

No abstract