BACKGROUND: Chronic rejection limits the long-term success of cardiac transplantation and the underlying causes of the disease are unknown. Connective tissue growth factor (CTGF) is considered as a mitogenic and chemotactic factor for fibroblasts and is associated with cell proliferation and collagen synthesis.OBJECTIVE: To evaluate the role and significance of expression of CTGF in rat chronic rejection heart aliografta.DESIGN, TIME AND SETTING: A randomized controlled animal experiment was performed at the Laboratory Animal Center of the Second Xiangya Hospital between April and August 2007.MATERIALS: Twenty Wistar rats serving as donors and twenty Sprague-Dawely (SD) rats serving as recipients were included. An additional 10 Wistar rats were included as controls.METHODS: After intra-abdominal heterotopic heart transplantations, rats received cyclosporine A, mycophenolate, and methylprednisolone immunosuppression. Ten recipient rats were anesthetized and sacrificed for heart harvesting at 2 and 8 weeks postoperation, respectively.MAIN OUTCOME MEASURES: Coronary vessel density, fibrosis grade, and intimal occlusion were observed by hematoxylin-cosin staining and Van Gieson staining. Myocardial fibrosis was semi-quantitatively scored. CTGF expression was detected by immunohistochemistry. The associations between CTGF expression and allograft fibrosis and CAV formation were analyzed.RESULTS: Allografts harvested at 8-week post-surgery showed more obvious coronary intimal proliferation, fibrosis and higher CTGF expression compared with the 2-week allografts and the controls (P < 0.05-0.01 ) while the cardiac artery density was lower than the control group (P < 0.05). However, the control group in our study showed negligible CTGF expression. There were strong negative correlations between the gray value of CTGF protein expression and cardiac fibrosis and coronary intimal occlusion (r = -0.734, -0.713, P < 0.01), demonstrating that CTGF protein expression was positively correlated with cardiac fibrosis and coronary intimal occlusion.CONCLUSION: CTGF is expressed in cardiac myocyte with CAV. The increased expression of CTGF in the cardiac allograft is associated with CAV development and fibrosis formation and is involved in the pathogenesis of cbronic heart rejection

Objective To detect the expression of connective tissue growth factor (CTGF) in acute heart allograft rejection in rats and to investigate the relationship between CTGF expression and cardiac allograft fibrosis. Methods Sixteen Wister rats served as donors and another 16 Sprague-Dawely (SD) rats served as recipients. Intra-abdominal heterotopic heart transplantation was performed. All rats received 10 mg/(kg·d) cyclosporine,40 mg/(kg·d)CellCept, and 3 mg/(kg·d)methylprednisolone immunosuppression after the surgery. Ten allografts were harvested 2 weeks postoperation while 10 normal Wister rats served as controls. The paraffin sections of harvested heart specimens were stained with hematoxylin and eosin (HE),and van Gieson(VG) for the examination of morphological changes to observe the lumen loss of myocardial coronary arteries and myocardial fibrosis. The expression of CTGF was studied by immunnohistochemical method and was measured semi quantitatively. The correlation between the CTGF expression and allograft fibrosis was studied. Results The allografts showed a typical symbol of acute rejection with excessive granulocyte infiltration around the vessel wall and myocardial interstice. There were also intimal proliferation and obvious fibrosis in the acute group and the differences between the acute and control group were significant (P<0.05). The expression of CTGF protein was mainly located around the vascular and myocardial lesions in the acute group while the control group showed no CTGF expression. The gray scale value of CTGF was (AR vs NH: 103.52±6.42 vs. 182.61±8.72,P<0.05). Strong negative correlations were found between the gray scale value and fibrosis formation(r=-0.734,P<0.01). Conclusion CTGF was overexpressed in acute allograft rejection rat hearts and might be involved in the pathogenesis of transplanted heart fibrosis.

Objective To analyze the reasons and treatment methods of high transprothetic pressure gradient after aortic valve replacement. Methods The clinical data of 45 patients with high transprothetic pressure gradient after aortic valve replacement were retrospectively analyzed. The patients were followed up for average 24.6 (12 - 40) months. The postoperative effective orifice area (EOA) of artificial valve was measured by transthoracic color Doppler ultrasound. Compared with published referred EOA of different artificial valve, there were 2 kinds results:measured EOA=referred EOA and measured EOA0.85 cm2/m2 and EOAI<0.85 cm2/m2. The reasons of high transprothetic pressure gradient were analyzed according to the above different standard. Results In the 45 patients with high transprothetic pressure gradient after aortic valve replacement, prosthesis-patient mismatch (PPM) was in 33 cases, and prosthetic dysfunction was in 10 cases, among whom 5 cases were because of thrombus (3 cases improved after increasing the dosage of warfarin, 2 cases underwent re-aortic valve replacement), 3 cases were because of severe bioprosthetic calcification (underwent re-aortic valve replacement), and 2 cases were because of prosthetic ring pannus and influenced movement of the leaflets (underwent re-aortic valve replacement). High flow in the left ventricular outflow tract occurred in 2 cases. The patients had no obvious discomfort, and did not receive special treatment. Four cases died, among whom 2 cases were because of severe PPM, and the other 2 cases were because of noncardiac. Conclusions Many reasons can result to the high transprothetic pressure gradient, and the PMM is the most common reason. Choosing the right treatment plan can improve the survival rate of patients.

To analyze the components of tumor infiltrating T lymphocyte (TIL) cells in malignant pleural effusion of lung adenocarcinoma, and evaluate their killing activities to autologous tumor cells. 
 Methods: Malignant pleural effusions were collected from 17 patients with lung adenocarcinoma. Mononuclear cells were isolated by Ficoll density gradient centrifugation and flow cytometer was used to analyze TIL cell components. TIL and tumor cells were separated through adherent culture. The tumor cells were identified via intramuscular injection of adherent cells into nude mice and the killing effect of cultured lymphocytes on autologous tumor cells was studied.
 Results: Of the TIL in malignant pleural effusions, T cells accounted for 60.6%-79.3%, while T helper cells were significantly higher than T killer cells (36.63%±1.90% vs 24.64%±2.32%, P<0.001). There were also natural killer (NK) cells and NK T cells in the effusions. Tumor cells were successfully isolated and cultured. The killing activity of cultured TIL to autologous tumor cells was 39.14%±12.04%, and the killing activity of TIL with high proliferation rate to autologous tumor cells was higher than that of low proliferation group (50.51%±3.80% vs 29.04%±5.77%, P<0.001).
 Conclusion: T lymphocytes are the major components of TIL in malignant pleural effusions derived from lung adenocarcinoma, and T helper cells are more than T killer cells. The killing activity of TIL with strong proliferation ability to autologous tumor cells is higher than that of TIL with weak proliferation ability. Therefore, cells from malignant pleural effusions could be used for cellular immunotherapy against tumor.
Adenocarcinoma of Lung ; Animals ; Cytotoxicity, Immunologic ; Humans ; Interleukin-2 ; Lung Neoplasms ; Mice ; Mice, Nude ; Pleural Effusion, Malignant ; T-Lymphocytes

Antibody-mediated rejection (AMR) is a rare and serious complication after lung transplantation, with no characteristic of pathological manifestation, no systematic standard treatment, and the poor efficacy and prognosis. We reported a case of early AMR after lung transplantation and the relevant literature has been reviewed. A male patient presented with symptoms of cold 99 days after transplantation and resolved after symptomatic treatment. He admitted to the hospital 14 days later because of a sudden dyspnea and fever. Anti-bacteria, anti-fungi, anti-virus, and anti-pneumocystis carinii treatment were ineffective, and a dose of 1 000 mg methylprednisolone did not work too. The patient's condition deteriorated rapidly and tracheal intubation was done to maintain breathing. Serum panel reactive antibody and donor specific antibody showed postive in humen leukocyte antigen (HLA) II antibody. Pathological examination after transbronchial transplantation lung biopsy showed acute rejection. Clinical AMR was diagnosed combined the donor-specific antibody with the pathological result. The patient was functionally recovered after combined treatment with thymoglobuline, rituximab, plasmapheresis, and immunoglobulin. No chronic lung allograft dysfunction was found after 3 years follow up. We should alert the occurrence of AMR in lung transplantation recipient who admitted to hospital with a sudden dyspnea and fever while showed no effect after common anti-infection and anti-rejection treatment. Transbronchial transplantation lung biopsy and the presence of serum donor-specific antibody are helpful to the diagnosis. The treatment should be preemptive and a comprehensive approach should be adopted.
Graft Rejection ; Graft Survival ; HLA Antigens ; Humans ; Isoantibodies ; Lung Transplantation/adverse effects* ; Male