Recipient intramuscular cotransfection of transforming growth factor beta1 and interleukin 10 ameliorates acute lung graft rejection.

Objective: Multiple gene transfer might permit modulation of concurrent biochemical pathways involved in acute lung graft rejection. We investigated whether gene cotransfection into the recipient reduces acute lung graft rejection.

Methods: Brown Norway rats were used as donors, and F344 rats were used as recipients.

Gene transfer of tumor necrosis factor inhibitor improves the function of lung allografts.

Background: Tumor necrosis factor is an important mediator of lung transplant acute rejection. Soluble type I tumor necrosis factor receptor binds to tumor necrosis factor-alpha and -beta and inhibits their function. The objectives of this study were to demonstrate efficient in vivo gene transfer of a soluble type I tumor necrosis factor receptor fusion protein (sTNF-RI-Ig) and determine its effects on lung allograft acute rejection.

Recipient intramuscular administration of naked plasmid TGF-beta1 attenuates lung graft reperfusion injury.

Background: Gene therapy may be an effective strategy for modulating lung graft ischemia-reperfusion injury. We investigated whether recipient intramuscular (IM) naked plasmid gene transfer of transforming growth factor beta1-active (TGF-beta1-active) ameliorates lung graft ischemia-reperfusion injury.

Methods: Preliminary studies in F344 rats demonstrated that gastrocnemius muscle transfection of TGF-beta1-active produced muscle and plasma protein expression at 24 and 48 hours after transfection.

Adenovirus encoding soluble tumor necrosis factor alpha receptor immunoglobulin prolongs gene expression of a cotransfected reporter gene in rat lung.

Objective: Because almost all pulmonary diseases are not caused by one gene, multiple gene transfection is required for current gene therapy. Adenovirus is an important gene therapy vector, but a short duration and the inability of repeated administration remain limitations. The aims of this study were to evaluate whether adenoviral vector encoding soluble tumor necrosis factor alpha receptor immunoglobulin and beta-galactosidase cotransfection prolongs gene expression and facilitates repeated vector administration to investigate the feasibility of a cotransfection strategy.

Tumor necrosis factor inhibitor gene transfer ameliorates lung graft ischemia-reperfusion injury.

Objective: Tumor necrosis factor is an important mediator of lung transplant ischemia-reperfusion injury, and soluble type I tumor necrosis factor receptor binds to tumor necrosis factor and works as a tumor necrosis factor inhibitor. The objectives of this study were to demonstrate that gene transfer of type I tumor necrosis factor receptor-IgG fusion protein reduces lung isograft ischemia-reperfusion injury and to compare donor endobronchial versus recipient intramuscular transfection strategies.

Methods: Three donor groups of Fischer rats (n = 6/group) underwent endobronchial transfection with either saline, 2 x 10(7) plaque-forming units of control adenovirus encoding beta-galactosidase, or 2 x 10(7) plaque-forming units of adenovirus encoding type I tumor necrosis factor receptor-IgG fusion protein.

Intratracheal adenovirus-mediated gene transfer is optimal in experimental lung transplantation.

Objective: Gene transfer to experimental lung grafts has been shown to reduce ischemia-reperfusion injury and acute rejection. The optimal delivery route should produce high lung expression with no inflammation and minimal systemic expression. The goal of this study was to determine the optimal gene transfer route for use in experimental lung transplantation.

Intramuscular gene transfer of interleukin-10 reduces neutrophil recruitment and ameliorates lung graft ischemia-reperfusion injury.

Interleukin-10 (IL-10) has potent anti-inflammatory properties but its direct effects on neutrophil trafficking in lung transplant ischemia-reperfusion (I/R) injury are unknown. This study was performed to determine if recipient intramuscular IL-10 gene transfer reduces neutrophil infiltration in lung isografts and ameliorates I/R injury. Twenty-four hours before transplantation, recipient rodents received intramuscular injection with 1 x 10(10) plaque-forming units (pfu) adenovirus encoding human IL-10 (hIL-10), 1 x 10(10) pfu adenovirus control encoding p-galactosidase, or saline.

Recipient intramuscular cotransfection of naked plasmid transforming growth factor beta1 and interleukin 10 ameliorates lung graft ischemia-reperfusion injury.

Objective: Multiple gene transfer might permit modulation of concurrent biochemical pathways involved in lung graft ischemia-reperfusion injury. In this study we analyzed whether recipient intramuscular naked plasmid cotransfection of transforming growth factor beta(1) and interleukin 10 would result in amelioration of lung graft ischemia-reperfusion injury.

Methods: Forty-eight hours before transplantation, 6 groups (n = 6) of F344 rats received intramuscular injection of naked plasmid encoding chloramphenicol acetyltransferase, chloramphenicol acetyltransferase plus beta-galactosidase, transforming growth factor beta(1), interleukin 10, or transforming growth factor beta(1) plus interleukin 10 or were not treated.

Risk factors for conversion of laparoscopic to open cholecystectomy.

Background: Laparoscopic cholecystectomy (LC) has become the treatment of choice for symptomatic gallstones; however conversion to open cholecystectomy (OC) remains a possibility. Unfortunately, preoperative factors indicating risk of conversion are unclear. Therefore, we aimed to identify risk factors associated with conversion of LC to OC.

Low-dose endobronchial gene transfer to ameliorate lung graft ischemia-reperfusion injury.

Objective: This study was undertaken to determine whether low-dose endobronchial transfer to the donor of the gene for human interleukin 10 would decrease ischemia-reperfusion injury in lung transplantation.

Methods: Experiments used male Fischer rats. Donor animals underwent right thoracotomy.