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Effects of media conditioned by a non-metastasizing human salivary gland adenocarcinoma cell clone and metastasizing clones from salivary gland and various other tissues on the proliferation, migration and protease production of bovine aortic endothelial cells in vitro.

We demonstrate the role in tumor-associated angiogenesis of factors released into conditioned medium (CM) from in vitro human salivary gland cell clones with biological phenotypes ranging from non-metastasizing to metastasizing. A non-metastasizing human salivary gland adenocarcinoma cell clone HSGc and its subclone with metastatic potential (Gc2-100 cl-1) were employed. We also used metastasizing cell clones obtained by explant cultures of organs of Gc2-100 cl-1 tumor-bearing nude mouse. The proliferation and migration of bovine aortic endothelial (BAE) cells were significantly stimulated by the addition of CM obtained from Gc2-100 cl-1 and metastasizing cell clones, while CM from HSGc was ineffective. When the effect on protease secretion by BAE cells was examined, CM from Gc2-100 cl-1 and metastasizing cell clones inhibited the secretion of type IV collagenases by BAE cells much more than did CM from HSGc. These findings, therefore, may imply that Gc2-100 cl-1 and metastasizing cell clones secrete angiogenic factors that stimulate not only the proliferation and migration of endothelial cells but also the formation of basement membrane components necessary for the reconstruction of new blood vessels at migrated sites of endothelial cells by preventing the degradation of basement membrane component, type IV collagen.

Adenocarcinoma↗

Expression of androgen, estrogen, and progesterone receptors in salivary gland tumors. Frequent expression of androgen receptor in a subset of malignant salivary gland tumors.

The expression of sex hormone receptors in some tumors suggests a role for these receptors in tumor pathogenesis and therapy. Previous studies of the expression of estrogen and progesterone receptors in salivary gland tumors have reported conflicting results. We evaluated the immunohistochemical expression of androgen, estrogen, and progesterone receptors (AR, ER, and PR) in a series of 78 formalin-fixed, paraffin-embedded salivary gland tumors. Immunoreactivity for AR was seen in 14 of 14 carcinoma ex pleomorphic adenomas, 6 of 6 salivary duct carcinomas, and 2 of 2 basal cell adenocarcinomas but in only 2 of 10 acinic cell carcinomas, mucoepidermoid carcinomas, and adenoid cystic carcinomas each. AR expression was distributed evenly between the sexes. ER and PR were expressed in only a few cases of salivary gland tumors. All 26 benign salivary gland tumors were negative for AR, ER, and PR. The uniform expression of AR exclusively in a subset of malignant salivary gland tumors suggests a possible role for AR in the histogenesis and possibly in the clinical management of these malignant salivary gland tumors.

Adenocarcinoma↗

[Pleomorphic adenoma of the minor salivary gland].

Minor salivary gland tumors represent about 10-15% of salivary gland tumors. The most frequently seen histological type are pleomorphic adenomas, which are usually located at the hard palate. Clinical and pathological features of 7 cases are reviewed.

Adenoma, Pleomorphic↗

Salivary gland ultrasonography in the evaluation of primary Sjögren's syndrome. Comparison with minor salivary gland biopsy.

OBJECTIVE: To evaluate the diagnostic accuracy of ultrasonography (US) of the salivary glands versus histologic examination in detection of salivary gland involvement in primary Sjögren's syndrome (SS). METHODS: Thirty female patients with primary SS diagnosed according to the European criteria and 30 female subjects of similar age with dry mouth (symptomatic controls) due to other selected disorders were studied. Evaluation of salivary involvement was by 2 independent observers for both the parotid and submandibular glands using US score (range 0 to 4) that assigns points to the different degree of glandular inhomogeneity. Lip salivary gland (LSG) biopsies were graded according to the Chisholm and Mason classification system and by morphometric analysis. The area under receiver operating characteristic (ROC) curve was employed to evaluate the screening method's performance. RESULTS: Through ROC curves salivary gland US arose as the best performer, followed by the volume percentage of inflammatory cells and by the semiquantitative focus score. The difference between area under ROC curve of salivary gland US and lymphocytic focus score was significant (p = 0.044), reflecting the accuracy of the imaging diagnostic assessment. No differences arise between areas under the ROC curve of salivary gland US and volume percentage of inflammatory cells (p = 0.610) and between volume percentage of inflammatory cells and semiquantitative focus score (p = 0.081). Attempts to assess the independent contribution of the fractional composition of the LSG biopsy as the predictor of US score showed a significant contribution of both the fractional composition of inflammatory infiltrate (p = 0.01) and intralobular ducts (p = 0.02). These findings indirectly suggest that the US abnormalities we found were strongly related to SS. CONCLUSION: These results conclusively indicate that quantitative assessment of salivary gland ultrasonography is a very useful method fdr evaluating salivary gland involvement in SS and can replace other diagnostic techniques, such as sialography or salivary scintigraphy.

Adult↗

[Quantitative functional exploration of the salivary glands. Measurement of salivary elimination of technetium 99].

The authors propose a method for the quantitative functional exploration of the salivary glands using two objective criteria, on the one hand the level of fixation in the parotid of technetium 99m injected in the form of its pertechnate and on the other hand by the fraction of radioactivity found in different specimens of saliva collected in the course of a test carried out using a pharmacological agent free of toxic effects--lemon juice. The quantitative results obtained and its simplicity render the method particularly useful in evaluating the course of salivary function in all forms of disorder, pathological or iatrogenic.

Arthritis, Rheumatoid↗

Glial fibrillary acid protein immunoreactivity in fine-needle aspiration of salivary gland lesions: a useful adjunct for the differential diagnosis of salivary gland neoplasms.

The value of immunocytochemical staining for glial fibrillary acid protein (GFAP) in salivary gland lesions was investigated in 33 fine-needle aspiration smears. The study utilized cytologic material from ten pleomorphic adenomas, six normal salivary glands, three cases of chronic sialadenitis, three Warthin's tumors, two adenoid cystic carcinomas, three adenocarcinomas, two malignant mixed tumors, one acinic cell carcinoma, and three mucoepidermoid carcinomas. All tested pleomorphic adenomas stained positively. The adenoid cystic carcinomas and the cases of chronic sialadenitis, along with the low-grade mucoepidermoid carcinoma, were negative for GFAP immunoreactivity. These results indicate that immunostaining for GFAP may be a valuable aid in the diagnosis of pleomorphic adenoma; GFAP may be especially helpful in distinguishing those cases for which the differential diagnosis includes the aforementioned salivary gland neoplasms.

Adenoma↗

The specificity of adhesive interactions between rat lymphocytes and salivary gland epithelia.

Salivary immune responses depend on localization of immunocytes in salivary glands. We tested effects of anti-adhesion molecule antibodies and several ligand analogs on in vitro adherence of rat thoracic duct lymphocytes (TDL) to parotid and submandibular gland sections. While TDL adherence to both tissues was markedly decreased by anti-L-selectin mAbs, binding ability after removal of L-selectin by chymotrypsin or PMA suggested that other adhesion systems were involved. Integrin involvement in parotid interactions was indicated by inhibitory effects of anti-HEBF(PP), LFA-1, ICAM-1, and alpha4 integrin antibodies as well as by the PMA-enhanced adherence. Anti-Thy-1 partially inhibited TDL binding to parotid gland, and anti-CD44 partially inhibited submandibular binding. The majority of salivary gland-bound TDL were sIg+ B cells. FACS analysis showed differences in parotid and submandibular endogenous lymphocyte adhesion molecule expression with greater percentages of L-selectin, HEBF(PP), alpha4 integrin, LFA-1, ICAM-1, CD44, and Thy-1-positive cells present in parotid gland. While precise roles of known or novel adhesion molecules in salivary gland lymphocyte retention are not clear, these data suggest that selectins (parotid, submandibular), integrins (parotid), Thy-1 (parotid), and CD-44 (submandibular), as well as other unidentified molecules, are involved.

Animals↗

Coexpression of vimentin, cytokeratin and S-100 in monomorphic adenoma of salivary gland; value of marker studies in the differential diagnosis of salivary gland tumours.

An unusual coexpression of glial fibrillary acid protein (GFAP), keratin and vimentin occurs in pleomorphic adenoma of salivary gland. We designed this study to see if coexpression of the markers was also present in monomorphic adenoma of the salivary gland and whether monomorphic adenoma could be distinguished from other salivary gland tumours by marker studies. Immunocytochemical markers were used on fine needle aspiration samples from four cases of monomorphic adenoma, two cases of oncocytic adenoma, three cases of adenoid cystic carcinoma and four cases of pleomorphic adenoma. While positivity for cytokeratin, vimentin and S-100 was consistently found in all cases of monomorphic adenoma, only cytokeratin was expressed in adenoid cystic carcinoma. In pleomorphic adenoma, GFAP, cytokeratin and vimentin were coexpressed while in cases of oncocytic adenoma none of the markers was localized. Thus, it appears that by using a combination of GFAP, cytokeratin, vimentin and S-100 a distinction between these neoplasms may be possible. However, a larger study is needed to establish the usefulness of this approach.

Adenoma↗

Bcl-2 family expression in salivary glands from patients with primary Sjögren's syndrome: involvement of Bax in salivary gland destruction.

To investigate the molecular mechanism of glandular parenchyma destruction in Sjögren's syndrome (SS), Bcl-2, Bax, Bcl-X, and Bak expression were studied. SS (n = 18) and control salivary glands (n = 6) were examined by immunohistochemistry. Apoptosis was assessed by in situ DNA nick end labeling. Infiltrating mononuclear cells in the SS salivary gland showed elevated Bcl-2. These mononuclear cells expressed increased Bax but did not undergo apoptosis. Both SS and control salivary gland ductal epithelial cells expressed Bcl-2, Bax, and Bcl-X. SS, but not normal, salivary gland acinar cells expressed Bax and underwent apoptosis. These results suggest that elevated Bax expression in SS salivary gland acinar cells may play an important role in the apoptotic pathway. In contrast, Bcl-2 expression in SS infiltrating mononuclear cells and ductal cells may contribute to their survival.

Apoptosis↗

The clinical value of quantitative dynamic scintigraphy in salivary gland disorders.

Salivary gland scintigraphy with [99mTc]pertechnetate was performed in a group of 11 subjects without any known salivary pathology, and in a group of 12 xerostomic patients. Time-activity curves, normalized to background, were generated for each of the four major salivary glands in both groups, and averaged into single curves, representing the function of each gland. Comparing the two sets of curves (patients vs controls) demonstrates that utilizing our "normalization" approach enables one not only to determine whether one group of dynamic curves is significantly different from another, but to decide which of the glands are normal and which are malfunctioning. The sensitivity, specificity, accuracy and predictive values of this procedure are all above 0.90.

Adult↗

Fine-needle aspiration biopsy of large-cell undifferentiated carcinoma of the salivary glands: presentation of two cases, literature review, and differential cytodiagnosis of high-grade salivary gland malignancies.

Primary undifferentiated carcinoma of the salivary glands is a rare, high-grade neoplasm which accounts for a very small number (1-5.5%) of malignant salivary gland tumors. The large-cell variant (LCU) is less well-characterized than the small-cell form. We report on the fine-needle aspiration (FNA) biopsy findings of 2 cases of LCU, one arising in the parotid gland, and the other in a buccal mucosa accessory salivary gland. The 2 cases were similar in composition: isolated and loosely cohesive large cells with abundant cytoplasm, and variability pleomorphic nuclei with prominent nucleoli. One case also featured multinucleated tumor giant cells and macrophage polykaryons; the latter has not previously been described in FNA biopsies of LCU. There was no evidence of squamous, myoepithelial, or widespread mucinous differentiation by morphological, cytochemical, or immunohistochemical analyses (focal rare mucin production identified on special stains in one case). The differential diagnosis is lengthy and consists of other high-grade primary salivary gland malignancies as well as metastatic lesions, including melanoma. The pattern of immunohistochemical reactivity (positive keratin, negative S-100, and HMB-45 antigens), and lack of conspicuous mucin production of significant lymphoidinfiltrate, were useful in establishing the correct diagnosis.

Aged↗

[Functional activity of the salivary glands of Drosophila melanogaster in the course of metamorphosis: a comparative electrophoretic analysis of the proteins of the salivary glands, fat body and hemolymph].

The proteins of the salivary gland secretion at the moment of puparium formation and the protein composition of the salivary glands, fat-body and hemolymph during the III larval instar and 12 hours prepupal period were investigated by means of electrophoresis in polyacrilamide gel, in the presence of urea. Both the qualitative and quantitative differences in the protein composition of the salivary glands were found which appeared to be due to the change of functions of the salivary glands in the process of development. 69 protein fractions were isolated in the salivary gland secretion, 40 of them being PAS-positive. A correlation was noted between the appearance of the first PAS-positive fractions at the stage of 95-100 hrs (from the moment of egg laying) and the cytological demonstration of PAS-positive secretion granules. New glycoproteins appeared in the salivary glands in prepupae (2 hrs after the puparium formation) and, later, in the hemolymph. A complicated pattern of the secretion formation in the salivary glands of the III instar larvae and possible change of its composition during metamorphosis are discussed.

Adipose Tissue↗

Phosphatidylinositol-hydrolysing enzymes in blowfly salivary glands.

The salivary glands of adult blowflies (Calliphora erythrocephala) contain enzymes that hydrolyse phosphatidylinositol, predominantly by a Ca2+-independent deacylation, though a Ca2+-dependent phosphodiesterase (phospholipase C) activity could be detected. The deacylating enzymes could also hydrolyse phosphatidylcholine and phosphatidylethanolamine, and were secreted in the saliva. Homogenization of salivary glands prelabelled with [3H]inositol resulted in a rapid deacylation of the endogenous 3H-labelled phosphatidylinositol; this hydrolysis was unaffected by addition of 5-hydroxytryptamine to the homogenate.

Animals↗

The induction of host resistance to tick infestation with a salivary gland antigen.

Salivary gland antigen, SGA, derived from partially engorged female Dermacentor andersoni was shown to be capable of inducing resistance to tick infestation in guinea pigs never previously exposed to ticks. Immunization regimens involved the administration of SGA by different routes and with or without the use of adjuvants. Induced resistance was expressed by significantly fewer larvae engorging, and the weight of larvae which did engorge was reduced. Salivary gland antigen has been shown to interact with the immune effector elements of animals which acquired and expressed tick resistance due to infestation. These findings demonstrated the potential for an immunologic approach to tick control.

Adjuvants, Immunologic↗

Characterization of murine autologous salivary gland graft cells: a model for use with an artificial salivary gland.

The purpose of this study was to examine the growth and key functional abilities of primary cultures of salivary epithelial cells toward developing an artificial salivary gland. Cultures of epithelial cells originating from submandibular glands of BALB/c mice were established. Parenchymal cells were isolated by a Percoll gradient technique and thereafter seeded on irradiated NIH 3T3 fibroblasts serving as a feeder layer. The isolated cells were termed autologous salivary gland epithelial (ASGE) cells and could be cultivated for at least five passages (time limit of experiments). ASGE cells presented the typical organizational behavior of epithelial cells and electron microscopy, as well as immunostaining for cytokeratins, confirmed their epithelial origin. Furthermore, measurements of transepithelial resistance and water permeability indicated the ability of the ASGE cells to form a functional epithelial barrier. This study suggests that primary salivary epithelial cells can be obtained that exhibit critical characteristics needed for use with an artificial secretory device.

Animals↗

Developmental aspects of fluid and electrolyte secretion in salivary glands.

The salivary glands of rodents undergo considerable cytodifferentiation after birth and are useful models for the study of functional development, including the mechanisms of fluid and electrolyte secretion. In the rat submandibular gland, secretion of salivary fluid cannot be elicited until approximately 2 weeks of age. The currently accepted model of salivary fluid secretion indicates that this process depends on the activation, on stimulation of cholinergic receptors, of several ion transport systems, resulting in a net transport of osmotically active ions (primarily Cl- and Na+) across the acinar epithelium. This creates the necessary osmotic gradient for the transacinar movement of water. The process is associated with a signal transduction pathway involving the formation of phosphoinositide products (primarily inositol triphosphate or IP3) and the mobilization of Ca2+. The latter regulates monovalent ion conductances (K+, Cl-), which are critical for the secretory process. Immature submandibular glands and cells of early postnatal rats have a lower density of cholinergic receptors and release less K+ and Cl- than mature cells and gradually develop other ion transport systems (such as a Na, K, 2Cl cotransport system) involved in the secretory process. Surprisingly, they form more IP3 and show a larger increase in cytosolic Ca2+ when stimulated with maximal or supramaximal concentrations of agonist. Therefore, they show some interesting dissociations in the signal transduction mechanism that suggest differences in the coupling between receptors and membrane phosphoinositides, between IP3 and IP3-dependent Ca2+ stores, and between the Ca2+ signal and the monovalent ion transport systems which are critical for secretion.

Acetylcholine↗