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The Study On Pathogenesis Of Condyloma Acuminata

Posted on:2004-03-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:H F XieFull Text:PDF
GTID:1104360092987027Subject:Internal Medicine
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As a common sexual transmitted disease, Condyloma Acuminata (CA) is caused by Human Papilloma Virus (HPV), but the pathogenesis of CA is still not very clear. Some researches showed that there was an imbalance of Th1/Th2 cytokines and local immumity abnormity in CA patients, so we try to further study the serum levels of IL-10 and IFN-y and the level of apoptosis in perpheral blood mononuclear cells (PBMC). On the other hand , CA is one kind of benign hyperplastic disease, so the abnormal cell apoptosis and proliferation may take roles in the development and recurrence of CA. The expressed proteins may change in keratinocyte with HPV in CA lesions. So we took the following studies: (1) Apoptosis and telomerase activity and their relativity in CA patients. (2) Effect of BCG-PSN on serum levels of IL-10 and IFN- in CA patients. (3) Effect of BCG-PSN on apoptosis of PBMC in CA patients. (4) Preteome techniques was used to investigate the expression changes of certain proteins between normal tissues and C A lesions.Part 1 :Apoptosis and telomerase activity in patients with CA.Methods: Choose 60 patients with CA randomly. Telomerase activitiesin tissues of 60 CA lesions and 30 normal controls were assayed using telomeric repeat amplification polymerase chain reaction (TRAP)-ELISA. Terminal deoxynucleotidyl transferase (TdT)-mediated biotin dUTP nick end-labeling (TUNEL) was used to detect apoptotic cells in CA lesionsand normal controls; The expression of Fas , FasL and TRAIL was investigated with immunohistochemistry technique.Results: (1) Telomerase activity was increased significantly in CA compare with that in normal control. Apoptosis keratinocytes were found in 48 cases (80%) and negative correlation was found between telomerase activity and apoptotic index (r=-0.515 , P=0.004); (2) The expression of Fas was seen in 100% (60/60) of CA tissues and none of normal tissues. 76.7% (46/60) of CA tissues and none of normal tissues expressed FasL. 70% (42/60) of CA tissues and none of normal tissues expressed TRAIL. There was a negative correlation between the infiltration degree of mononuclear cells (MNCS) in the epidermis and the intension of FasL and TRAIL staining ( r - -0.506 and r =-0.450 respectively, P <0.05).Conclusion: (1) Telomerase activity and apoptosis is increased in condyloma acuminata than in normal control. (2) Fas antigen (Fas) mediates apoptosis. Fas, FasL and TRAIL may be involved in the regulation of apoptosis and may play an important role in the occurence and recurrence of CA. (3) The FasL/TRAIL expressed in keratinocytes induced apoptosis in Fas/TRAILR-expressing target cells by binding to the cell membrane receptors and recombinant forms of these ligands may potentiate the effect of chemotherapeutic drugs.Part 2: Effect of BCG-PSN on serum levels of IL-10 and IFN- y in CA patientsMethods: 60 CA cases were divided into two groups randomly : treatment group (BCG-PSN+regular antiviral treatment + electrocautery) and control group (regular antiviral drugs + electrocautery). Double-antibody sandwich ELISA was used to detect the serum levels of interleukin-10 and interferon gamma.Recults: Compared with normal control, serum level of interleukin-10 in patients with CA before treatment was increased significantly, while serum levels of interferon-gamma was significantly decreased. There was a significantly negative correlation between the levels ofIL-10 and IFN- (r= -0.269,P<0.05). After treatment, the level of interleukin-10 in the treatment group was decreased significantly and the level of IFN- was increased significantly.Conclusion: BCG-PSN could modulate the imbalance of cytokines, which can lead to inhibitory effect on a series of cell-immune responses and recurrence of CA.Part 3: Effect of BCG-PSN on apoptosis of perpheral blood mononuclear cells in patients with CA.Methods: 60 patients with CA were randomly divided into two groups (consistent with part 2). The expression of Fas/FasL and TRAIL in PBMC were detected by i...
Keywords/Search Tags:Condyloma acuminatum, Human papillomavirus, Telomerase, Apoptosis, Fas, Fas ligand, TRAIL, BCG-PSN, interleukin-10, interferon gamma, proteome, 2-DE
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