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The Effects Of HCMV Infection On The Phenotypes Of Host Cells In Vivo And In Vitro And Its Mechanisms

Posted on:2005-06-18Degree:DoctorType:Dissertation
Country:ChinaCandidate:G R YangFull Text:PDF
GTID:1104360122495803Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
Hodgkin's lymphoma (HL) is one of lymphoid malignant tumors that forms less than 1% of all de novo neoplasms occurring mainly among young children in developing courtry and among young adults in developed country. According to its characteristic histology, HL is devided into two main types in update WHO Classification of Tumors: nodular lymphocyte predominant HL (NLPHL) and classical HL (CHL). Its diagnosis is based on the identification of characteristic and diagnostic multinucleated giant cells that are called Reed-Sternberg cells (RS cells) within an inflammatory milieu. Both RS cells and mononucleated neoplastic cells (called Hodgkin's cells and showing similar cytological features to RS cells) form HRS cells. The tumor population includes HRS cells and a number of neoplastic cell variants. Molecular studies have recently shown that in most if not all cases RS cells, Hodgkin's cells, and cell variants belong to the same clonal population, which is derived from peripheral B and T cells in about 98% and 2% of cases, respectively. However, studies on phenotypes of HRS cells show that HRS cells are obviously different from its origin, B lymphocytes in germinal center in phenotypes. Which mechanism is involved in this phenotypic alteration? It is very important to find the answer in morphogenesis of HRS cells and even in patiiogenesis of HL. It is well-known that pathogenesis of HL is related to infections of many viruses in which Epstein-Barr virus (EBV) has recently been the object of intense research activity. But EBV genome is only detectable in up to 50% of Hodgkin's disease cases in the Western populations. Even in developing countries, not all Hodgkin's disease cases are positive for EBV. Since 1990s, Prof. Huang Gaosheng et al have found the presence of hCMV in Reed-Sternberg cells and their variants by several methods. So a new area has been opened in studies of etiology and pathogenesis of HL.Human cytomegalovirus (HCMV) belongs to B herpesvirus subfamily. As a widespread human pathogen, HCMV is responsible for generally asymptomatic and persistent infections in healthy children and adults,although it is the cause of some cases of mononucleosis in some people who receive HCMV-contaminated blood products. HCMV can cause serious disease in individuals absent of an effective immune response and in fetuses. In addition, HCMV is associated with a number of human cancers including cervical carcinoma, prostatic carcinoma, colon adenocarcinoma, Kaposi's sarcoma and Hodgkin's lymphoma. HCMV has a wide range of cell permissivity. Being the targets of HCMV's selective tropism, duct epithelial cell of salivary gland is most commonly infected. In host cell, HCMV infection not only leads to morphological changes but also leads to the alterations of cellular function. The functional alterations in host cells caused by HCMV consist of cellular responses to virus-host cell receptor interactions, modulation of host cell transcription and protein synthesis, effects on cellular proliferation, alterations in cellular membranes, and virus-induced apoptosis. However, studies about effects of HCMV on cellular immunophenotype have not been found yet.In this study, firstly we investigated elaborately the effects of HCMVinfection on duct epithelial cell of salivary gland, and then by using the results as a disease control we studied prelimilarily immunophenotypic alterations of HRS cells in HL and the relationship between immunophenotypic alterations and HCMV infection. All the results will be used as a base in further studies about the effects of HCMV on the immunophenotypic alterations of HRS cells in HL. The contents and results included in this study are shown as below:I Using cytomegalic inclusion disease in parotid (PCID) as the disease model, we evaluated prelimilarily the effects of HCMV on phenotypes of duct epithelial cells of parotid glandII cases of PCID autopsy specimen were used. In Hematoxylin-eosin staining, typical morphological changes could be found clearly. Some pillar epithelial cells enlarged in...
Keywords/Search Tags:Human cytomegalovirus, salivary gland epithelial cell, Hodgkin's lymphoma, HRS cell, immunophenotype, alteration, cathepthin D
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