Narihisa Yamada

Giant mediastinal bronchial artery aneurysm mimicking benign esophageal tumor: a case report and review of 26 cases from literature

Mediastinal bronchial artery aneurysm is rare but potentially life-threatening, and requires prompt treatment to avert rupture with catastrophic results. A 78-year-old man was referred to our hospital with a benign esophageal tumor, which appeared as an extrinsic, extramucosal filling defect on an esophagogram. Chest computed tomography and selective bronchial arteriography led to a definitive diagnosis of mediastinal bronchial artery aneurysm. Aneurysmectomy and closure of the ostia of both the afferent and efferent bronchial arteries was performed via standard posterolateral thoracotomy. Postoperative course was uneventful, and the patient was discharged on the seventh postoperative day.

Thymidine Phosphorylase Gene Transfer Inhibits Vascular Smooth Muscle Cell Proliferation by Upregulating Heme Oxygenase-1 and p27KIP1

Objective—Thymidine phosphorylase (TP) reportedly promotes endothelial cell migration and induces heme oxygenase (HO)-1 expression. However, its effect on vascular smooth muscle cells (VSMCs) is poorly understood. In this study, we examined the effect of TP on VSMCs in vitro and in vivo. Methods and Results—Phagemid vector encoding human TP gene was transfected into rat VSMCs, and a clone overexpressing TP was selected (C2). C2 showed a slower migration and proliferation than VSMCs cloned with empty vector (pC) under basal, serum-stimulated, and hypoxic conditions. This decrease in proliferation correlated with TP-induced HO-1 expression and was reversed by inhibitors of either TP or HO activity. Furthermore, in C2, the cyclin-dependent kinase inhibitor (p27KIP1) was much more abundant than in pC, and the cell cycle was arrested at the G1 phase. TP or HO activity inhibitors decreased p27KIP1 expression in C2 to the level seen in pC. Adventitial TP gene delivery significantly reduced neointimal VSMC migration and neointima formation in balloon-injured rat carotid arteries. Conclusions—TP overexpression upregulated HO-1 expression and consequently increased p27KIP1 in cultured VSMCs, and inhibited VSMC migration and proliferation in vitro and in vivo. TP represents a promising target for treating vascular obstructive disease.

Adventitial delivery of platelet-derived endothelial cell growth factor gene prevented intimal hyperplasia of vein graft

BACKGROUND Platelet-derived endothelial cell growth factor (PD-ECGF), also known as thymidine phosphorylase (TP) reportedly inhibits vascular smooth muscle cells (VSMCs) migration and proliferation. We hypothesized that adventitial administration of the PD-ECGF/TP gene will suppress intimal hyperplasia and prevent vein graft failure. METHODS The study used 68 female rabbits. Rabbit jugular vein was autogenously transplanted into carotid artery with a cuff anastomotic technique. To define vascular wall gene transfer efficiency, poloxamer hydrogel (20%) containing plasmid vector encoding the LacZ gene and different concentrations of trypsin (0%, 0.1%, 0.25%, and 0.5%, n = 5 for each group) was applied to the adventitia of the vein graft. Gene transfer efficiency was evaluated 7 days later by X-gal staining. An additional 48 rabbits received poloxamer hydrogel (20%) containing 0.25% trypsin and the human PD-ECGF/TP gene, LacZ gene, or saline. Intima thickness was evaluated at 2 and 8 weeks after grafting (n = 8 for each group at each time point). Transgene expression was examined by reverse transcriptase-polymerase chain reaction, immunoblotting assay, and immunohistochemical staining. Immunohistochemical staining was also used to determine VSMC proliferation, heme oxygenase-1 expression, and macrophage infiltration. RESULTS Incorporation of trypsin into the poloxamer hydrogel significantly increased vessel wall gene transfer. Trypsin at 0.25% and 0.5% resulted in higher gene transfer at the same level without effecting intimal hyperplasia and inflammation; thus, trypsin at 0.25% concentration was used for subsequent experiments. Compared with the LacZ and saline groups, grafts receiving the PD-ECGF/TP gene significantly reduced intimal thickness at 2 and 8 weeks after treatment. The ratio of proliferative VSMC was lower in PD-ECGF/TP treated grafts. Histologic examination of the PD-ECGF/TP transgene grafts demonstrated high expression of heme oxygenase-1, which has been reported to inhibit VSMC proliferation, suggesting that heme oxygenase-1 may be important in the inhibition effect of PD-ECGF/TP on VSMC. No neoplastic or morphologic changes were found in the remote organs. CONCLUSIONS A safe and highly efficient gene transfer method was developed by using poloxamer hydrogel and a low concentration of trypsin. Neointimal hyperplasia was significantly reduced by adventitial application of the PD-ECGF/TP gene to the vein graft. Our data suggest that adventitial delivery of the PD-ECGF/TP gene after grafting may be promising method for preventing vein graft failure.

Long‐term effect of gene therapy for chronic ischemic myocardium using platelet‐derived endothelial cell growth factor in dogs

We previously reported the 2‐week benefits of platelet‐derived endothelial cell growth factor (PD‐ECGF) gene therapy in chronically ischemic myocardium. However, the long‐term effects and safety using this gene have not been reported.

Renal redox dysregulation in AKI: application for oxidative stress marker of AKI

Oxidative stress is a major determinant of acute kidney injury (AKI); however, the effects of an AKI on renal redox system are unclear, and few existing AKI markers are suitable for evaluating oxidative stress. We measured urinary levels of the redox-regulatory protein thioredoxin 1 (TRX1) in patients with various kinds of kidney disease and in mice with renal ischemia-reperfusion injury. Urinary TRX1 levels were markedly higher in patients with AKI than in those with chronic kidney disease or in healthy subjects. In a receiver operating characteristic curve analysis to differentiate between AKI and other renal diseases, the area under the curve for urinary TRX1 was 0.94 (95% confidence interval, 0.90-0.98), and the sensitivity and specificity were 0.88 and 0.88, respectively, at the optimal cutoff value of 43.0 μg/g creatinine. Immunostaining revealed TRX1 to be diffusely distributed in the tubules of normal kidneys, but to be shifted to the brush borders or urinary lumen in injured tubules in both mice and humans with AKI. Urinary TRX1 in AKI was predominantly in the oxidized form. In cultured human proximal tubular epithelial cells, hydrogen peroxide specifically and dose dependently increased TRX1 levels in the culture supernatant, while reducing intracellular levels. These findings suggest that urinary TRX1 is an oxidative stress-specific biomarker useful for distinguishing AKI from chronic kidney disease and healthy kidneys.

Controlling Air Leaks Using Free Pericardial Fat Pads as Surgical Sealant in Pulmonary Resection

BACKGROUND This study evaluated the feasibility and efficacy of a new operative method for controlling intraoperative air leaks using free pericardial fat pads as a covering sealant in pulmonary resection. METHODS To manage air leaks that must be controlled in pulmonary resection at the first water sealing test, collected free pericardial fat was used as a covering sealant and sewn on by the suture closing the lesion. In cases of uncontrolled air leaks at the second sealing test, fibrin glue was used to fill the residual lesion between the fat and visceral pleura. Fifty-one eligible patients were enrolled in this study to evaluate the duration of postoperative air leaks and the condition of the implanted fat on chest computed tomography (CT) 6 months later. RESULTS The mean duration of postoperative air leaks was 1.05 ± 1.84 days in the 39 cases that received the pericardial fat covering technique only and 2.66 ± 3.42 days in the 12 cases that received the pericardial fat covering technique combined with fibrin glue. Prolonged alveolar air leaks occurred in 1 case and 2 cases, respectively. No cases required conversion to conventional methods, and there were no further adverse events. On follow-up chest CT approximately 62.7% of obvious engrafted fat survived. CONCLUSIONS Using free pericardial fat pads as a sealant to control air leaks in pulmonary resection is safe and has good feasibility and potent efficacy. This new method can be an innovative technique for preventing prolonged air leaks.

Thrombosed abdominal aortic aneurysm associated with an extensively "shaggy" aorta repaired anatomically via a thoracoabdominal approach with supraceliac aortic clamping: report of a case.

A 76-year-old man with a history of multiple laparotomies and severe coronary artery disease was referred to our hospital after the sudden development of pain and numbness in the lower extremities. Computed tomography showed a thrombosed abdominal aortic aneurysm and diffuse aortic atherosclerosis; compatible with a “shaggy aorta.” A good response to thrombolytic therapy permitted elective scheduling of abdominal aortic surgery after coronary artery bypass grafting. We operated via an extended left retroperitoneal approach through a thoracoabdominal incision. Epiaortic ultrasonography revealed that only the supraceliac aorta was free of mobile thrombi and had minimal plaque; we therefore placed a proximal aortic cross-clamp there. Anatomic aortic reconstruction was then performed successfully using an aorto-biiliac graft to restore adequate distal blood flow. There were no vital-organ ischemic complications, and the postoperative course was satisfactory.