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PubMed1984

Differential regulation of alpha 2u globulin gene expression in liver, lachrymal gland, and salivary gland.

The alpha 2u globulins, products of a highly homologous multigene family, are synthesized in the liver and submaxillary salivary glands of the rat. Although their precise function has not been ascertained, they are of interest because of the complex developmental and hormonal regulation of their tissue levels. We now report that alpha 2u globulin is synthesized in a third tissue of the rat, the extraorbital lachrymal gland. Immunocytochemical studies indicate that the distribution of alpha 2u globulin is more homogeneous in the lachrymal gland than in the liver or submaxillary gland. In situ hybridization to alpha 2u globulin RNA reveals specific signal only over the acinar cells of the lachrymal gland. Several different isoelectric forms of alpha 2u globulin are encoded by lachrymal gland mRNA. The major lachrymal and salivary gland isoforms are indistinguishable from one another, but more acidic than the hepatic isoforms. In addition, analysis of double-stranded cDNAs with a diagnostic restriction-enzyme pair detects no differences between the alpha 2u globulin mRNAs of lachrymal and salivary gland, but clearly distinguishes these from their hepatic counterparts. In spite of the similarity between the lachrymal and salivary gland alpha 2u globulin gene products, we find that the hormonal and developmental regulation of alpha 2u globulin expression differs markedly in these two tissues. In the liver, where a different subset of alpha 2u globulin genes is expressed, a third regulatory phenotype is observed.

Alpha-Globulins↗
PubMed1976

On the occurrence of argyrophil cells in salivary glands.

Salivary glands (parotid, submandibular and sublingual glands) of nine mammalian species were investigated with respect to presence and localization of argyrophil and argentaffin cells. With the exception of the parotid gland of the rat, no positive staining was observed within the examined glands. In the rat parotid distinctly argyrophil cells could be demonstrated in the intercalated ducts. Histochemical studies of the cells, ultrastructural analysis of their cytoplasmic granules as well as their reactions to certain drugs indicate that these cells are of exocrine rather than of endocrine nature. After a subcutaneous injection of pilocarpine, the intensity of the argyrophil staining was markedly reduced. No specific catecholamine fluorescence could be detected within the cells, not even after pretreatment of the animals with high doses of L-DOPA. The membrane-bounded cytoplasmic granules of the intercalated duct cells furthermore displayed a strong positive staining reaction after treatment of ultrathin Vestopal sections with the periodic acid-chromic acid-silver technique of Rambourg et al. (1969).

Animals↗
PubMed2006

Rapamycin control of transgene expression from a single AAV vector in mouse salivary glands.

Salivary glands (SGs) appear to be a useful target site for gene therapeutics. The ability to control transgene expression is essential for clinical application. Previously, in a proof-of-concept study, we have shown that the rapamycin-inducible transcriptional regulation system can regulate protein expression after adenoviral-mediated gene transfer to SGs. To evaluate the potential ability to utilize this regulatory system for long-term control of transgene expression in this tissue, we employed a 'third generation', single adenoassociated serotype 2 viral (AAV2) vector encoding human erythropoietin (hEPO) under the control of a rapamycin-inducible promoter. The vector, rAAV-TF2.3-hEPO (10(10) particles/animal), was delivered to mouse SGs. No detectable increase in serum hEPO or hematocrit levels was observed in the absence of rapamycin administration. However, rapamycin induced elevation of serum hEPO levels, as well as concomitant hematocrit changes, that were dose-dependent, completely reversible, and relatively stable over the course of this study (6 months), with no appreciable change in rapamycin responsiveness. Our results suggest that the rapamycin transcriptional regulation system delivered in a single AAV2 vector to SGs may be valuable for systemic protein replacement applications.

Adenoviridae↗
PubMed2003

Distinct localization of MUC5B glycoforms in the human salivary glands.

Salivary mucins, encoded by the MUC5B gene, make up a heterogeneous family of molecules, which are secreted by several glands, including the submandibular, sublingual, and palatine glands. Previous studies have shown that heterogeneity in the salivary mucin population is related to its multiglandular origin. In the present study we address the question to what extent the mucin (MUC5B) population from a single human salivary gland is made up of different glycoforms. Using monoclonal antibodies to defined protein and sulfated carbohydrate epitopes specific to MUC5B, we conduct an immunohistochemical study of different salivary gland types, including submandibular, sublingual, and labial glands. In all tissues studied we found a mosaic expression pattern of sulfo-Lewis a antigen, recognized by mAb F2, which in salivary glands is exclusively present on MUC5B. On the other hand, mucous acini were uniformly labeled by mAb EU-MUC5Bb, evoked against a peptide-stretch of the tandem repeat region of MUC5B. Double staining with both antibodies confirmed the presence of MUC5B-positive/sulfo-Lewis a-positive cells, as well as MUC5B-positive/sulfo-Lewis a-negative cells within one glandular unit. These results indicate that one and the same salivary gland synthesizes different MUC5B glycoforms.

Antibodies, Monoclonal↗
PubMed1977

Irradiation-induced changes in human salivary glands.

Salivary tissue shows inflammatory changes, atrophy, replacement fibrosis, marked pleomorphism and atypia of the acinar epithelium and oncocytic metaplasia in the months following irradiation. The ductular epithelium undergoes squamous changes and within the ductular lumina, secretions become inspissated. The underlying pathogenetic mechanisms for these late irradiation induced changes may be the combination of a direct irradiation effect on acinar epithelium in association with post-obstructive inflammation and ischaemia, secondary to irradiation-induced endarteritis; however, these morphological changes observed may only be the result of an unusual repair phenomenon that salivary tissue is known to go through after any form of noxious stimulation. These histological alterations may lead to a possible misdiagnosis of malignancy in surgical specimens.

Atrophy↗
PubMed1992

Expression of S-100 protein, epithelial membrane antigen, carcinoembryonic antigen and alpha fetoprotein in normal salivary glands and primary salivary gland tumors.

The distribution of S-100 protein, epithelial membrane antigen, carcinoembryonic antigen and alpha fetoprotein was studied in 38 primary salivary gland tumors. S-100 protein, a useful marker of myoepithelial cells, was demonstrated in some benign tumors. Carcinoembryonic antigen expression was consistently positive in adenoid cystic carcinoma. Demonstration of epithelial membrane antigen helped to confirm the epithelial nature of some neoplastic cells. Alpha fetoprotein was not expressed in any of the cases examined. No correlation was found between immunopositivity and tumor behavior in the present series.

Adenoma↗
PubMed1987

Immunohistochemistry and ultrastructure of myoepithelium and modified myoepithelium of the ducts of human major salivary glands: histogenetic implications for salivary gland tumors.

The organization of salivary gland ducts, especially the presence or absence of myoepithelial cells, is central to histogenetic approaches to the classification of salivary gland tumors. Striated and excretory ducts are reported to be devoid of myoepithelial cells but do contain basal cells. To investigate the nature of such basal cells, tissue sections of normal human salivary glands were examined by means of immunohistochemical, ultrastructural, and fluorescent microscopic techniques. With the use of a mouse monoclonal anticytokeratin antibody (3 12C8-1) that, in salivary glands, is specific for myoepithelial cells, these cells associated with acini and intercalated ducts were strongly stained, as were the basal cells of striated and excretory ducts in each case. Ultrastructurally, some basal cells of both striated and excretory ducts had narrow, elongated cellular processes or the main portion of the cell containing parallel arrays of microfilaments with linear densities and micropinocytotic vesicles, whereas in other basal cells tonofilament bundles predominated. A similar range of cytoplasmic features existed in myoepithelial cells associated with acinar and intercalated duct cells. In addition, some duct basal cells have a complement of actin filaments similar to classic myoepithelium of acini and intercalated ducts. Striated and excretory ducts of human salivary glands, therefore, contain fully differentiated and modified myoepithelial cells, both of which express a specific cytokeratin polypeptide that is absent from duct luminal and acinar cells. Differentiation patterns in the intralobular and interlobular ducts suggest that these regions of salivary gland parenchyma cannot be excluded as histogenetic sites for the induction of salivary gland tumors in which neoplastic myoepithelial cells have been shown to have a major role.

Epithelium↗
PubMed1996

Expression of S-100 protein and glial fibrillary acidic protein in cultured submandibular gland epithelial cells and salivary gland tissues. Histogenetic implication for salivary gland tumors.

S-100 protein and glial fibrillary acidic protein (GFAP) were studied in human salivary gland tissues and human cultured submandibular gland epithelial cells. Immunohistochemically, ductal cells in normal salivary gland tissues were positive for S-100 protein and GFAP, but myoepithelial cells were uniformly negative. Immunocytochemically, cultured submandibular gland ductal cells were positive for S-100 protein and GFAP. By immunoblotting analysis of the cultured cell lysates, a 6.5-kd S-100 protein was detected. This band corresponded to S-100 protein purified from bovine brain. The cultured submandibular gland cells expressed 49- and 54-kd GFAP polypeptides. These results have important implications for the histogenesis of salivary gland tumors.

Animals↗
PubMed1964

LEAKAGE OF TRANSMITTERS IN SALIVARY GLANDS.

Salivary secretion evoked by sympathetic stimulation or by injection of guanethidine, adrenaline or synephrine is slightly reduced by parasympathetic antagonists in doses which abolish the secretory responses to stimulation of the parasympathetic nerve. Similarly, an adrenaline antagonist caused a small diminution of the salivary flow elicited by parasympathetic stimulation or by injection of methacholine chloride. Secretion caused by pilocarpine could be accelerated by physostigmine. We conclude that transmitter leaks in subliminal concentrations, as far as secretion is concerned, from the sympathetic and parasympathetic postganglionic nerve endings.

Acetylcholine↗
PubMed1986

Large calculi of the submandibular salivary glands.

Salivary calculi occur in the submandibular and parotid glands, and their ducts, and occasionally reach a large size. However, little information is available on the composition of these giant stones. 2 cases are reported of unusually large calculi of the submandibular salivary glands. The glands were excised, and the results of chemical and infrared analysis of the calculi are presented.

Aged↗
PubMedDate not supplied

Isolation, identification, and synthesis of PDVDHFLRFamide (SchistoFLRFamide) in Locusta migratoria and its association with the male accessory glands, the salivary glands, the heart, and the oviduct.

An amidated decapeptide, exhibiting strong inhibitory activity of spontaneous visceral muscle movements, was isolated from 9000 brain-corpora cardiaca-corpora allata-subesophageal ganglion complexes of the migratory locust, Locusta migratoria. During the process of HPLC purifications, the biological activity of the fractions was monitored using the isolated hindgut of the cockroach Leucophaea maderae. The primary structure of this myotropic peptide is Pro-Asp-Val-Asp-His-Val-Phe-Leu-Arg-Phe-NH2 and is identical to SchistoFLRFamide isolated from the grasshopper, Schistocerca gregaria. It shares the carboxy-terminal sequence FLRFamide with several identified peptides from different phyla. At this moment, six decapeptides isolated from different insect species are identical at 7 of the 10 amino acid residues (X-D-V-X-H-X-FLRFamide). The cockroach, fly, and locust peptides differ only by the N-terminal amino acid residue. Synthetic SchistoFLRFamide showed biological as well as chemical characteristics indistinguishable from the native peptide. It provoked a decrease in frequency and amplitude of contractions of the locust oviduct. By means of a polyclonal antiserum directed against the carboxy terminal of SchistoFLRFamide, we demonstrated that the male accessory glands, the heart, the oviduct, and the salivary glands were innervated by axons containing SchistoFLRFamide-like immunoreactivity. Administration of SchistoFLRFamide elicited an immediate effect on the basal membrane potential of the opalescent tubule gland cells.

Amino Acid Sequence↗
PubMed1997

Assessment of proliferative activity using the MIB1 antibody help to distinguish polymorphous low grade adenocarcinoma from adenoid cystic carcinoma of salivary glands.

Salivary polymorphous low grade adenocarcinoma (PLGA) and adenoid cystic carcinoma (AdCC) bear a superficial histological and immunophenotypic resemblance to each other, but can usually be separated by conventional microscopic examination. However, this is not always so, such as with PLGAs displaying plentiful cribriform structures, and when only limited tissue from small biopsies is available for study. Twenty-one cases of PLGA and 20 cases of AdCC from the surgical pathology files in Plzen, Exeter and Helsinki were incubated with the MIB1 antibody using the supersensitive avidin-biotin peroxidase technique after microwave pretreatment. The antibody recognizes the cell cycle associated antigen Ki-67 on routinely processed formalin-fixed paraffin-embedded tissues. The percentage of positively stained tumor cell nuclei constituted the MIB1 index. It was found that the PLGAs had a mean MIB1 index of 2.4% (range 0.2-6.4), while the AdCCs had a mean value of 21.4% (range 11.3-56.7). Within the PLGA group, the 12 tumors which did not form micropapillae had a somewhat lower mean MIB1 index (1.4%) than those nine in which such structures constituted a significant but minor component (3.4%). These results indicate that the MIB1 index was significantly higher in the AdCCs than the PLGAs and that the figures showed no overlap zone. We conclude, therefore, that immunohistochemical staining with the MIB1 antibody appears to be a potentially useful supplementary diagnostic tool in differentiating difficult cases of PLGA from AdCC.

Adenocarcinoma↗
PubMed1997

Oral pilocarpine HCl stimulates labial (minor) salivary gland flow in patients with Sjögren's syndrome.

Pilocarpine HCl has been shown to stimulate parotid and submandibular gland salivary flow. The purpose of this study was to determine whether this cholinergic-muscarinic drug also stimulates labial (minor) salivary gland (LSG) flow and to relate that with whole unstimulated salivary (WUS) flow rates. Subjects diagnosed with primary Sjögren's syndrome (SS-1; n = 9) or secondary Sjögren's syndrome (SS-2; n = 9) were enrolled in this study after meeting stringent enrollment criteria. An age-gender matched control group was also enrolled. The labial saliva was collected in a standardized manner on Periopaper for 5 min and the volume was analysed by the Periotron. Whole unstimulated salivary samples were collected for 5 min by the method of Mandel and Wotman (1976). Each subject was dosed with pilocarpine HCl (5 mg; tablets; p.o.). After 60 min the LSG flow as well as the WUS flow was determined again as previously. The results indicated a significant (> 180%) increase in both labial salivary gland flow as well as whole salivary flow in the SS-1 and SS-2 subjects (mean +/- s.e.m.): [SS-1: WUS = 0.1080 +/- 0.03 vs 0.2242 +/- 0.03 ml per 5 min; LSG = 93.1 +/- 22.2 vs 167.8 +/- 15.9 microliters/5 min; P < 0.001; SS-2: WUS = 0.1384 +/- 0.02 vs 0.2775 +/- 0.09 ml per 5 min; LSG = 97.7 +/- 20.2 vs 182.8 +/- 17.9 microliters per 5 min; P < 0.001]. These results indicate a significant increase in labial salivary gland flow as well as whole salivary flow as stimulated by pilocarpine HCl in Sjögren's syndrome patients.

Adult↗
PubMed1993

HIV-salivary gland disease. Salivary scintiscanning with technetium pertechnetate.

The salivary disease in two patients with human immunodeficiency virus infection was investigated by technetium pertechnetate scintiscanning. Although there was good histologic evidence of benign lymphoepithelial disease, scintiscanning failed to delineate any salivary lesions. Technetium pertechnetate scintiscanning seems to be of little value in the detailed investigation of salivary disease in human immunodeficiency virus infection, though gallium scanning can help. Fine needle aspiration or biopsy remain the main diagnostic tools.

AIDS-Related Opportunistic Infections↗