Thrombin-induced connective tissue growth factor expression in human lung fibroblasts requires the ASK1/JNK/AP-1 pathway.

Thrombin plays an important role in lung inflammatory diseases. Thrombin can induce connective tissue growth factor (CTGF) expression in lung fibroblasts. However, little is known about the signaling pathway in thrombin-induced CTGF expression. In this study, we investigated the role of apoptosis signal-regulating kinase 1 (ASK1) in thrombin-induced CTGF expression in human lung fibroblasts. Thrombin caused a concentration- and time-dependent increase in CTGF expression in WI-38 cells and primary lung fibroblasts. Thrombin-induced CTGF expression and CTGF-luciferase activity were inhibited by a protease-activated receptor 1 antagonist (SCH79797), the dominant-negative mutants (DNs) of ASK1 and JNK1/2, and an AP-1 inhibitor (curcumin). Thrombin caused ASK1 Ser(967) dephosphorylation, the dissociation of ASK1 and 14-3-3, and a subsequent increase in ASK1 activity. Thrombin induced increases in JNK phosphorylation and kinase activity, which were attenuated by ASK1DN. Furthermore, SCH79797 diminished the thrombin-induced ASK1 and JNK activities. Thrombin-induced CTGF-luciferase activity was predominately controlled by the sequence -747 to -184 bp upstream of the transcription start site of the human CTGF promoter and was attenuated by transfection with the deleted AP-1 binding site construct. Thrombin caused increases in c-Jun phosphorylation, the formation of an AP-1-specific DNA-protein complex, and the recruitment of c-Jun to the CTGF promoter. Furthermore, thrombin-mediated AP-1 activation was inhibited by ASK1DN, JNK1/2DN, and SP600125. These results suggest for the first time that thrombin, acting through protease-activated receptor 1, activates the ASK1/JNK signaling pathway, which in turn initiates c-Jun/AP-1 activation and recruitment of c-Jun to the CTGF promoter and ultimately induces CTGF expression in human lung fibroblasts.

Mediastinal teratoma with pulmonary involvement presenting as massive hemoptysis in 2 patients.

Massive hemoptysis is described in many disease processes. However, a mediastinal teratoma is rarely considered in a patient presenting with massive hemoptysis. Since a mediastinal teratoma has no specific symptoms, its definitive diagnosis is difficult before surgical intervention. Flexible bronchoscopy can be diagnostic in cases of a mediastinal teratoma with involvement of the bronchial tree. We report 2 cases of hemoptysis caused by mediastinal teratoma with bronchial communication.

Internal thoracic artery encircled by an unusual phrenic nerve loop.

We report an anatomic variation of the phrenic nerve. During a routine gross anatomical dissection course at our medical university, we found an unusual loop of the left phrenic nerve around the internal thoracic artery, about 1 cm from the take-off of the left subclavian artery. The phrenic nerve is close to the internal thoracic artery and is easily injured when dissecting the internal thoracic artery for coronary artery bypass conduit. Therefore, we suggest that the anatomic relationship of the phrenic nerve and internal thoracic artery is important in preventing incidental injury of the phrenic nerve.

Pulmonary valve endocarditis in a pregnant woman with a ventricular septal defect.

Bacterial endocarditis in pregnancy causes maternal and fetal mortality rates of 22.1% and 14.7%, respectively. The mortality rates differ according to the involved valves, and the size of vegetation has a prognostic correlation. This report is of a pregnant woman with an unrepaired ventricular septal defect and pulmonary valve endocarditis with a vegetation size of 3.29 cm. She and her baby were treated successfully. An emergency surgical plan would be appropriate for pregnant women in the third trimester with a large vegetation in the right side of the heart, and dental disease should be treated aggressively with appropriate prophylactic antibiotics.

Off-pump surgery for multiple coronary artery fistulas with aneurysm.

A 78-year-old woman presented with acute myocardial infarction, anterior wall, Killip III, with congestive heart failure. The finding of coronary angiographic examination was multiple congenital coronary artery fistulas with a huge aneurysm, with fistulas originating from both the right coronary artery and left anterior descending artery. The patient received surgery successfully without cardiopulmonary bypass. The finding of the pathologic examination revealed hyaline change in the aneurysmal vessel wall. In a two-year follow-up, the patient was found to be asymptomatic clinically with improved left ventricular function.

Clinical characteristics and treatment of constrictive pericarditis in Taiwan.

BACKGROUND: Constrictive pericarditis is an uncommon disease that prevents the normal diastolic filling of the heart and pericardiectomy is the only satisfactory treatment. METHODS AND RESULTS: The clinical characteristics and treatment of patients who underwent pericardiectomy for constrictive pericarditis (n = 23) were reviewed. Surgery was performed via left anterolateral thoracotomy plus transsternal extension in 3 patients, and median sternotomy in 20 patients. There were 2 deaths, resulting in an overall mortality rate of 8.7%. Of the 23 patients, 8 had Mycobacterium tuberculosis (Tb) infection, 2 had streptococcus infection, 1 had strongyloidiasis (Strongyloides stercoralis) and 1 developed the condition after a myocardial infarction; 2 patients underwent pericardial substitute insertion as post-heart surgery, and 3 patients had connective tissue disorders; 6 patients had idiopathic disease. CONCLUSION: These results show that bacterial infection, especially Tb, is a major etiology of constrictive pericarditis in Taiwan and that median sternotomy is an excellent approach for exposing the heart for pericardiectomy.