Increased extracellular levels of the novel proinflammatory cytokine high mobility group box chromosomal protein 1 in minor salivary glands of patients with Sjogren's syndrome.
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OBJECTIVE: To investigate the expression of the novel proinflammatory cytokine high mobility group box chromosomal protein 1 (HMGB-1) in the salivary glands of patients with Sjogren's syndrome (SS) and patients with sicca symptoms. METHODS: Biopsy samples from the minor labial salivary glands of patients with SS, patients with sicca symptoms but no diagnosis of SS, and healthy controls were investigated. Expression of HMGB-1, tumor necrosis factor (TNF), and interleukin-1beta (IL-1beta) was analyzed using immunohistochemical staining on consecutive cryosections. RESULTS: Increased expression of HMGB-1 was observed among the large infiltrates of mononuclear cells found in biopsy samples from patients with SS, and the degree of extracellular HMGB-1 was significantly higher in patients with SS compared with patients with sicca symptoms and with healthy controls (P < 0.05 and P < 0.01, respectively). Cellular expression of TNF was increased in patients with SS and in patients with sicca symptoms. In addition, the level of secreted TNF was significantly higher in patients with SS than in healthy controls (P < 0.05). Intracellular expression of IL-1beta was detected in all groups, while extracellular IL-1beta was observed almost exclusively among the infiltrating mononuclear cells of patients with SS. CONCLUSION: The increased amount of extracellular HMGB-1 observed in salivary glands of patients with SS indicates that HMGB-1 is involved in the inflammatory process of the disease. This cytokine, along with TNF and IL-1beta, may form a proinflammatory loop that promotes the chronic features of the glandular inflammation in SS. (+info)
Involvement of specific laminins and nidogens in the active remodeling of the basal lamina of labial salivary glands from patients with Sjogren's syndrome.
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OBJECTIVE: To investigate remodeling of the basal lamina of labial salivary glands (LSGs) from patients with Sjogren's syndrome (SS) by analyzing the expression of specific components that participate in its assembly and attachment to acinar and ductal cells. METHODS: Two groups of SS patients with similar levels of remnant glandular tissue but with low and high levels of interacinar fibrosis, respectively, were studied. The expression of laminin alpha1, alpha4, and gamma2 chains and nidogens was examined at the messenger RNA (mRNA) and protein levels. Nidogens 1 and 2 were also studied in situ by immunohistochemistry. RESULTS: Increases in the amount of mRNA and protein for both the processed and unprocessed laminin gamma2-chain were more pronounced in patients with low interacinar fibrosis. Increases in the protein levels of laminin alpha1 and alpha4 chains were observed in patients with low interacinar fibrosis, but not in those with high interacinar fibrosis. Nidogen mRNA and protein levels were similar in SS patients and controls. Interestingly, high levels of nidogen degradation were observed in patients with low interacinar fibrosis. Nidogens were readily detected by immunofluorescence in the basal lamina of the capillaries and stroma in SS patients, but were less apparent in the basal lamina of the acini and ducts. CONCLUSION: These results suggest that the basal lamina of LSGs from patients with SS is undergoing active remodeling, such that alterations are less evident in patients who have advanced morphologic signs of the disease (high interacinar fibrosis). Nidogen proteolysis might account for the disorganization of the basal lamina that is typically observed in LSGs from SS patients, assuming that cleavage impairs their ability to crosslink type IV collagen and laminin networks. (+info)
Overexpression of phosphorylated STAT-1alpha in the labial salivary glands of patients with Sjogren's syndrome.
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OBJECTIVE: To clarify the molecular mechanisms of Sjogren's syndrome (SS), we analyzed the functional role of the STAT-1 gene, one of the interferon-gamma (IFNgamma)-inducible genes, in labial salivary glands (LSGs) from SS patients. METHODS: The expression of STAT-1 messenger RNA (mRNA) was examined by real-time polymerase chain reaction (PCR) analysis, and the phosphorylation of STAT-1 protein (Tyr(701) and Ser(727) pSTAT-1) was investigated by Western blot and immunohistochemical analyses. The expression of IFNgamma-inducible 10-kd protein (IP-10), IFN regulatory factor 1 (IRF-1), and Fas was also examined by real-time PCR and immunohistochemical analyses. RESULTS: STAT-1alpha and STAT-1beta mRNA were highly expressed in LSGs from SS patients. The level of STAT-1alpha protein in SS LSGs was higher than that in 3 control LSGs, whereas STAT-1beta protein was not clearly detected by Western blot analysis. Moreover, Tyr(701) and Ser(727) pSTAT-1alpha proteins were specifically detected in SS LSGs. Immunohistochemical analysis showed localization of Tyr(701) pSTAT-1 in infiltrating lymphocytes and the adjacent ductal epithelium from SS patients. Ser(727) pSTAT-1 was localized only in the ductal epithelium of SS LSGs. The STAT-1-inducible genes IP-10 and IRF-1 and the Fas genes were highly expressed in SS LSGs and were colocalized with Ser(727) pSTAT-1-positive, but not Tyr(701) pSTAT-1-positive, cells. CONCLUSION: We found evidence of the up-regulation of STAT-1alpha mRNA and protein in LSGs from SS patients, as well as the presence of pSTAT-1alpha in ductal epithelium from SS patients. Our findings suggest that STAT-1alpha, especially Ser(727) pSTAT-1, may function as a key molecule in the pathogenesis of SS. (+info)
Myoepithelioma of minor salivary gland--an immunohistochemical analysis of four cases.
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INTRODUCTION AND METHODS: We performed an immunohistochemical study in four cases of myopitheliomas with objective to realize a profile in respect of differentiation grade by the monoclonal antibodies CK14, vimentin and alph-SMA, besides to investigate the cell proliferation by anti-PCNA, besides, we compare the immunoreactive with glandular normal tissue. RESULTS: In the glandular normal tissue the myoepithelials cells had shown expression for alpha-SMA and CK 14, while that in the ductals cells, only the presence of CK 14 was verified. All the cases was verified positivity for CK 14 and vimentin, however, CK 14 had been present only in epithelioid and fusiform cells, while that the vimentin revealed positive also in the cytoplasm of the plasmocytoid cells. alpha-SMA was not detected in the neoplasic cells. Immunopositivity for the PCNA was observed in more than 75% of the cellular component of the analyzed tumors, independent of the cellular type. CONCLUSIONS: We concluded that it did not have difference in the proliferative activity among the cellular types presents in the myoepitheliomas and, still, the results of this study suggest that the constituent cells of this neoplasia one really represent cells of the mioepitelial ancestry, but in different stages of differentiation. (+info)
Clear cell carcinoma of the base of the tongue: MR imaging findings.
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Clear cell carcinoma of the base of the tongue is a rare minor salivary gland neoplasm, and to our knowledge, the MR imaging appearance of this entity has not been described. We present the MR imaging findings in such a case and review the differential diagnosis for tongue base masses in an adult. (+info)
Pigmented mucoepidermoid carcinoma, a case report and review of the literature on melanin-pigmented salivary gland tumors.
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This paper reports a well-differentiated mucoepidermoid carcinoma containing numerous melanocytes in the parenchyma in a middle-aged Japanese man. In addition to the characteristic histopathologic features of well-differentiated mucoepidermoid carcinoma, various-formed and -sized, pigmented cells were widely distributed in the parenchyma. Many of these were considered to be melanocytes containing melanin in their cytoplasm. Perusal of the English-language literature revealed only four cases of salivary gland tumors with parenchymal pigmentation: three mucoepidermoid carcinomas and one pleomorphic adenoma. The possible histogenesis of melanocytes in the salivary gland lesions is discussed, although no firm conclusion could be drawn. (+info)
Rapidly progressive and metastatic mucoepidermoid carcinoma: application of serological tumor markers.
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Mucoepidermoid carcinoma (MEC) of the salivary gland is a rare entity. A distinction of 2 variants has been proposed: the low-grade tumor with a favourable prognosis and the high-grade tumor with a poor prognosis. Indeed, MEC is a cancer with a relative favourable outcome and more than 90% of patients survive for more than 5 years after diagnosis, reduced to about 70% after 10 years. This excellent prognosis might contribute to the unacceptable retention of the term "mucoepidermoid tumor" in the medical terminology, even in current medical textbooks. However, the distinction of MEC by grading is a guideline only and it is not appropriate to use this histological term as a prediction for individual cases. We describe the rapid fatal outcome of a patient with MEC in order to emphasize the malignant characteristics of this tumor and the possible application of tumor markers for the diagnosis of metastasizing MEC. (+info)
Low salivary dehydroepiandrosterone and androgen-regulated cysteine-rich secretory protein 3 levels in Sjogren's syndrome.
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OBJECTIVE: Sjogren's syndrome (SS), an autoimmune disease of exocrine glands, typically starts at the time of adrenopause. We undertook this study to test the hypothesis that SS is characterized by an insufficient androgen effect at the target tissue level. METHODS: We searched for androgen response elements (AREs) in the cysteine-rich secretory protein 3 (crisp-3) gene. Dehydroepiandrosterone (DHEA) responsiveness was experimentally studied using quantitative reverse transcriptase-polymerase chain reaction and immunofluorescence staining of human submandibular gland-derived acinar cells and labial salivary gland explants with or without DHEA. Finally, glandular and salivary CRISP-3 in healthy controls and SS patients was analyzed using immunohistochemistry, in situ hybridization, and enzyme-linked immunosorbent assay. Serum DHEA sulfate (DHEAS) and salivary DHEA levels were measured using a radioimmunometric method. RESULTS: Literature analysis and a search for AREs in gene banks suggested androgen dependency of human CRISP-3, and this was verified by studies of human submandibular gland acinar cells cultured with or without DHEA, in which DHEA increased CRISP-3 messenger RNA (mRNA) levels (P = 0.018). This finding was confirmed by the results of DHEA stimulation of labial salivary gland explants. Glandular CRISP-3 mRNA and protein labeling was weak and diffuse, coupled with low secretion in saliva (mean +/- SEM 21.1 +/- 2.7 mug CRISP-3/15 minutes in SS patients versus 97.6 +/- 12.0 mug CRISP-3/15 minutes in healthy controls; P < 0.0001). Compared with healthy controls, SS patients had low serum levels of DHEAS (P = 0.008) and also low salivary levels of DHEA (mean +/- SEM 224 +/- 33 pmoles versus 419 +/- 98 pmoles; P = 0.005). CONCLUSION: CRISP-3 pathology was seen in acini remote from lymphocyte foci and is apparently not secondary to local inflammation, but may represent some systemic effect in SS. Indeed, androgen deprivation in the salivary glands of SS patients is evidenced both by low salivary levels of DHEA and by low levels of DHEA-regulated CRISP-3. This may explain some of the characteristic features of SS. (+info)