Roles of human papillomavirus infection and stathmin in the pathogenesis of sinonasal inverted papilloma.

BACKGROUND: The purpose of this study was to investigate roles of human papillomavirus (HPV) infection and stathmin in sinonasal inverted papilloma (SNIP). METHODS: HPV DNA detection was performed by the fluorescence-based polymerase chain reaction (PCR) method. Stathmin protein expression was investigated by the immunohistochemistry method and mRNA expression of stathmin, Kif2a, and cyclin D1 were assessed by real-time PCR in SNIP and control subjects. RESULTS: The positive rate of HPV DNA detected in SNIP was about 53.6% (15 of 28). Recurrent cases showed a higher rate of HPV infection compared with initial cases and higher Krouse stage (T3 + T4) cases showed higher rate of HPV infection than lower Krouse stage (T1 + T2) cases. Stronger expression of stathmin, Kif2a, and cyclin D1 were observed in SNIP, especially HPV(+) SNIP. CONCLUSION: HPV infection was closely associated with recurrence and progression of SNIP. Stathmin is a valuable prognostic marker and could be considered as a therapeutic target in patients with SNIP.

Expression and regulation of interleukin-9 in chronic rhinosinusitis.

BACKGROUND: The pathogenesis of human chronic rhinosinusitis (CRS) remains controversial. Recent evidence has suggested that interleukin (IL)-9 is vital in eliciting inflammatory response, stimulating cell proliferation and preventing apoptosis, through binding to the IL-9 receptor (IL-9R). However, little is known about the roles of both molecules in the etiology of CRS. Therefore, this study aimed to assess IL-9 and IL-9R expression and determine their roles in the pathophysiology of CRS. METHODS: Immunohistochemistry was used to assess IL-9 and IL-9R immunolabeling. In addition, Western blotting and real-time polymerase chain reaction (PCR) were used for IL-9 and IL-9R protein and mRNA level quantitation, respectively, in CRS and control subjects. Furthermore, the effects of various stimulators at different concentrations and time on IL-9 were evaluated using nasal explant cultures. RESULTS: IL-9 and IL-9R were overexpressed in CRS, especially in CRS with nasal polyps. Interestingly, IL-9 expression was closely related to that of IL-9R. In addition, IL-9 mRNA levels were increased by treatment with IL-4, IL-17A, IL-1beta, and the IL-4 and transforming growth factor (TGF) beta1 combination, but suppressed by interferon gamma and IL-27. CONCLUSION: IL-9 and IL-9R were overexpressed in CRS at both protein and mRNA levels. In addition, IL-4, IL-17A, IL-1beta, and the IL-4 and TGF-beta1 combination contributed to increased IL-9 levels. Our findings indicate that IL-9 may play a proinflammatory role after IL-9R binding to induce mucosal epithelial cell growth, gland epithelial cell proliferation, and inflammatory cell infiltration in CRS. Future studies are required to further define the role of IL-9 in CRS etiology.

Downregulation of caveolin-1 in chronic rhinosinusitis with and without nasal polyps.

The pathogenesis of human chronic rhinosinusitis (CRS) remains controversial. Recent evidence has suggested that caveolin-1 (Cav-1) is a 22 kDa scaffolding protein and plays a pivotal role in host defense against infections and tumour suppression by reducing production of cyclin D1 and endothelial nitric oxide-synthase (eNOS). However, little is known about their roles in CRS. Therefore, we aimed to investigate the expression and role of Cav-1 in CRS. Cav-1 protein expression were investigated by immunohistochemistry method and mRNA expression of Cav-1, cyclin D1 and eNOS were assessed by real-time polymerase chain reaction in CRS and control subjects. Moreover, the effects of various stimulators with different concentrations and time on Cav-1 were evaluated on nasal explant culture. The results showed that weaker expression of Cav-1 protein and mRNA were observed in CRS, especially in CRS with nasal polyps (CRSwNP), stronger mRNA expression of cyclin D1 and eNOS were observed in CRS and Cav-1 expression was negatively related to cyclin D1 and eNOS expression, respectively. Cav-1 mRNA was augmented by IFN-γ, but supressed by IL-4 and IL-1ß. In conclusion, the expression of Cav-1 was downregulated in CRS and the role of Cav-1 was impaired in CRS, especially in CRSwNP, leading to the attenuation of inhibition effect on cyclin D1 and eNOS and resulted in the overexpression of cyclin D1 and eNOS. IFN-γ may be essential for Cav-1 gene expression.

Role of platelet-derived growth factor-α in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: The pathogenesis of human chronic rhinosinusitis with nasal polyps (CRSwNP) comprising eosinophilic CRSwNP (ECRSwNP) and non-eosinophilic (nECRSwNP) is not completely understood. Recent evidence has suggested that platelet-derived growth factor receptor alpha (PDGFRα) is implicated in cell growth, transformation, proliferation, migration, and vascular permeability and platelet-derived growth factor-A (PDGF-A) is a specific ligand for PDGFRα. However, little is known about their roles in CRSwNP. Therefore, we aimed to investigate the expression and role of PDGFRα and PDGF-A in CRSwNP. METHODS: PDGFRα protein expression was investigated by immunohistochemistry method and messenger RNA (mRNA) expression of PDGFRα and PDGF-A were assessed by real-time polymerase chain reaction (PCR) in CRSwNP patients and control subjects. Moreover, the effects of various stimulators with different concentrations and time on PDGFRα were evaluated on nasal explant culture. RESULTS: Quantitative analysis of immunostaining for PDGFRα showed an obvious elevation in immunolabeling of PDGFRα in CRSwNP groups compared with controls. Furthermore, PDGFRα protein was significantly stronger expressed in ECRSwNP group than nECRSwNP group and atopic patients showed stronger expression of PDGFRα protein than nonatopic patients. The mRNA of PDGFRα and PDGF-A were overexpressed in CRSwNP, especially in ECRSwNP. PDGFRα mRNA expression was closely related to PDGF-A mRNA. In nasal explant culture and stimulation, PDGFRα mRNA was augmented by interleukin 4 (IL-4), IL-5, or IL-1ß respectively, but suppressed by IL-27. CONCLUSION: PDGFRα may play a pivotal role in the pathophysiology of ECRSwNP and nECRSwNP by combining with PDGF-A. IL-4, IL-5, or IL-1ß may be critical for PDGFRα gene expression.

[The expression and significance of nephrin in hepatitis B virus-associated membranous nephropathy].

OBJECTIVE: To observe the expression of nephrin in hepatitis B virus-associated membranous nephropathy (HBV-MN), and investigate the impairment and significance of podocyte in HBV-MN. METHODS: The protein expression of nephrin in renal biopsy specimens in 35 patients, who were diagnosed as HBV-MN by renal biopsy, was determined by immunohistochemistry and tested by semi-quantitative method. The relationship between the expression of nephrin and clinicopathological data was analyzed. RESULTS: Among the 35 cases with HBV-MN, 6 were in MN phase I, 20 in MN phase II and 9 in MN phase III. A strong intensity expression of nephrin in normal glomerulus was found along capillary loop of glomerulus, while its expression in HBV-MN patients decreased obviously. There was no significantly difference in the expression of nephrin among the different stages of HBV-MN (P > 0.05). The expression of nephrin in different clinical types was significantly different(P < 0.05). The expression of nephrin in patients with nephrotic syndrome was significantly lower than that in patients without nephrotic syndrome (P < 0.01). The expression of nephrin in different grades of 24-hour urinary protein excretion quantity was significantly different(P < 0.05). There was negative correlation between the expression of nephrin and 24-hour urinary protein excretion quantity(r = -0.378, P < 0.05). In the patients with HBV-MN phase II, the expression of nephrin in patients with nephrotic syndrome was also significantly lower than that in patients without nephrotic syndrome (P < 0.01). CONCLUSIONS: The damage of podocytes emerge in the early stage of HBV-MN and the expression of nephrin in HBV-MN patients, especially in patients with nephrotic syndrome, are significantly down regulated. The descended expression of nephrin in HBV-MN patients may promote the production of proteinuria.

[Pathological features and ultrastructure of N-methyl-N-nitrosourea (MNU)-induced thymic lymphomas in mice].

The objective of study was to investigate the origin and to classify the subtype of N-methyl-N-nitrosourea (MNU)-induced thymic lymphomas in mice. Histopathologic, immunohistochemical and ultrastructural studies were performed to analyze the pathological features of the neoplasms. The results showed that the thymus in all cases became totally replaced by sheets of cells of the lymphoid series. All the tumors coexpressed CD3 and TdT. Transmission electron microscopic study showed the plasma membranes of malignant lymphoma cells were smooth. The nuclear profiles were usually regular, with varying percentage of convoluted nuclei. Few cell organoids were observed in cytoplasm. In conclusion, all the MNU-induced tumor classified by histopathologic, immunohistochemical and ultrastructural studies as precursor lymphoblastic lymphoma that were unquestionably related to the thymus origin and T-cell lineage.

[Significance of C4d deposition in the follicular lymphoma].

OBJECTIVE: To explore the significance of C4d deposition in follicular lymphoma (FL). METHODS: The deposition of C4d was detected in samples from 133 cases of lymphoma by immunohistochemistry and FL was studied by the double stainings of CD35/C4d, CD21/C4d and Bcl-2/C4d,respectively. RESULTS: Among the 26 FL tissues, irregular C4d deposition was seen in 19 tumor tissues. Double staining for CD35, CD21 or Bcl-2 showed the C4d deposition was around the follicular dendritic cells (FDC). There was no significant difference between the positive rate of C4d and the degree of lymphoma. No deposition was found in the diffuse areas of FL and other type lymphomas. CONCLUSION: C4d deposition around the follicular dendritic cell in the neoplastic follicles is a specific indicator of follicular lymphoma.