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Epithelial-myoepithelial carcinoma of the submandibular gland with a high uptake of 18F-FDG: a case report and image diagnosis.

Epithelial-myoepithelial carcinoma (EMC) is a rare low-grade malignant salivary gland neoplasm typically found in the parotid gland. This report describes a case of EMC that arose from the submandibular gland, and gives special emphasis to the preoperative diagnostic value of positron emission tomography (PET) in combination with computed tomography (CT) and magnetic resonance imaging (MRI). Although a preoperative diagnostically specific image of EMC could not be established, the malignant nature of this tumor was detected by these combined examinations.

Aged↗

[Ultrastructural morphometric study of sex dimorphism in cells of the ductus granulosus of the submandibular glands of mice].

The sexual dimorphism in the secretory cell of the granular convolated tubule of mouse submandibular gland was morphometrically studied in light and electronic microscope level. In semithin sections (0.5 micron) the nuclear volume (Bach, 1963) and the fractions of cellular volume occupied by the nucleus and by cytoplasm were determined (Chalkley, 1943). In twenty electronmicrographs per animal with a final magnification of x 15.000, using the Weibel's et al. (1966) multiproposition test system, were obtained relatives morphometrics data, which multiplied by the cytoplasmatic volume provided us the respective absolute values. The results showed a presence of a sexual dimorphism at subcellular level. The secretory cell of the male is higher and exhibit a greater volume when compared with that cells of the female. In the male that cells are characterized by a higher total volume of the endoplasmic reticulum, Golgi complex and secretory granules. The secretory granules and the condensation vacuoles size are more developed in male cells. The female secretory granular cells exhibit a greater absolute number of the condensation vacuoles and secretory granules, as well as, a higher mitochondria total volume and surface.

Animals↗

Histochemical localization of succinate dehydrogenase in the mouse submandibular gland during postnatal development.

The activity of succinate dehydrogenase (SDH) was examined histochemically in the parenchyma of murine submandibular gland (SMG) during postnatal development on light-microscopical level. In this study, SDH appears as a good marker of differentiating and mature striated ducts of both sexes and convoluted granular tubules of males. Enzyme activity in glandular parenchyma increased from the 1st day to the 7th week of postnatal life. Definitive enzymatic pattern was seen in the gland aged 7 weeks. Histochemical differences between male and female SMG of mouse were noted.

Aging↗

Distribution of nitric oxide synthase containing elements in the feline submandibular gland.

Combined nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and nitric oxide synthase (NOS) immunocytochemistry were used to study the distribution of nitric oxide synthesizing elements in the cat submandibular gland. A large number of thin varicose fibres, with intense staining for both markers, were seen around or in close contact with the acini. Some of the stained nerve fibres were associated with intra- and interlobular salivary ducts and blood vessels. All neurones in the submandibular ganglia showed intense staining for both NADPH-d and NOS. The epithelial layer of the salivary ductal branches and the endothelial lining of blood vessels were NOS immunonegative but NADPH-d positive. Our results suggest that NO might act as a neurotransmitter in the regulation of blood flow and secretion in the submandibular salivary gland.

Amino Acid Oxidoreductases↗

Expression of epidermal growth factor receptor in fetal mouse submandibular gland detected by a biotinyltyramide-based catalyzed signal amplification method.

Branching morphogenesis of the fetal mouse submandibular gland (SMG) can be modulated in vitro by stimulation or inhibition of the epidermal growth factor receptor (EGFR). Because the mRNAs for EGF and EGFR are detectable in RNA of SMG rudiments isolated directly from fetuses, the EGF system probably operates physiologically as a regulator of SMG morphogenesis. However, neither EGFR protein nor its precise cellular localization has been characterized in the fetal SMG. Here we show EGFR protein in fetal mouse SMG by immunoprecipitation, affinity labeling, ligand-induced autophosphorylation, and immunohistochemistry. SMGs from E16 fetuses (day of vaginal plug = E0) were labeled with [35S]-cysteine/methionine and homogenized. After addition of specific antibody to EGFR, the immunoprecipitate was isolated, resolved by polyacrylamide gel electrophoresis, and detected by autoradiography. A single band of 170 kD was detected, corresponding to the EGFR protein. Affinity labeling with [125I]-EGF of the membrane fraction of E18 SMG also revealed a prominent band at 170 kD, showing that this EGFR protein can bind specifically to its ligand. Incubation of SMG membranes from E18 fetuses with EGF in the presence of [gamma-32P]-ATP, followed by immunoprecipitation with anti-phosphotyrosine antibody also showed a single band at 170 kD, demonstrating autophosphorylation of the EGFR in response to binding of its ligand. Immunohistochemical localization of the cellular sites of EGFR in the fetal SMG required use of a catalyzed signal amplification procedure, with biotinyltyramide as the amplifying agent. EGFR was localized predominantly, if not exclusively, in cell membranes of epithelial cells of the rudiment, whereas staining of mesenchymal cells was equivocal. Staining was strongest on duct cells, and weak on cells of the end-pieces. These findings clearly show that a functional EGFR protein is expressed in fetal SMG chiefly, if not exclusively, on epithelial cells.

Affinity Labels↗

Membrane-specific regulation of Cl- channels by purinergic receptors in rat submandibular gland acinar and duct cells.

Measurement of [Cl-]i and the Cl- current in the rat salivary submandibular gland (SMG) acinar and duct cells was used to evaluate the role of Cl- channels in the regulation of [Cl-]i during purinergic stimulation. Under resting conditions [Cl-]i averaged 56 +/- 8 and 26 +/- 7 mM in acinar and duct cells, respectively. In both cells, stimulation with 1 mM ATP resulted in Cl- efflux and subsequent influx. Inhibition of NaKCl2 cotransport had no effect on [Cl-]i changes in duct cells and inhibited only about 50% of Cl- uptake in acinar cells. Accordingly, low levels of expression of NaKCl2 cotransporter protein were found in duct cells. Acinar cells expressed high levels of the cotransporter. Measurement of Cl- current under selective conditions revealed that acinar and duct cells express at least five distinct Cl- channels; a ClCO-like, volume-sensitive, inward rectifying, Ca2+-activated and CFTR-like Cl- currents. ATP acting on both cell types activated at least two channels, the Ca2+-activated Cl- channel and a Ca2+-independent glibenclamide-sensitive Cl--current, possibly cystic fibrosis transmembrane regulator (CFTR). Of the many nucleotides tested only 2'-3'-benzoylbenzoyl (Bz)-ATP and UTP activated Cl- channels in SMG cells. Despite their relative potency in increasing [Ca2+]i, BzATP in both SMG cell types largely activated the Ca2+-independent, glibenclamide-sensitive Cl- current, whereas UTP activated only the Ca2+-dependent Cl- current. We interpret this to suggest that BzATP and UTP largely activate Cl- channels residing in the membrane expressing the receptor for the active nucleotide. The present studies reveal a potentially new mechanism for transcellular Cl- transport in a CFTR-expressing tissue, the SMG. Coordinated action of the P2z (luminal) and P2u (basolateral) receptors can mediate part of the transcellular Cl- transport by acinar and duct cells to determine the final electrolyte composition of salivary fluid.

Adenosine Triphosphate↗

Hedgehog peptide promotes cell polarization and lumen formation in developing mouse submandibular gland.

Tube formation of the developing mouse submandibular salivary gland (SMG) begins at embryonic day (E) 14. The SMG of Sonic hedgehog (Shh) null mice was recently shown to fail to progress to stages beyond around E14. Here, we examined the effects of Shh peptide on tube formation of SMG explants. When the SMG rudiments from E14 mice were cultured, terminal buds of glands treated with Shh peptide formed the acini-like structure with a lumen whereas those of control glands remained as cell masses. In the acini-like terminal buds of the treated glands, tight junction proteins of ZO-1 and claudin-3 delineated the lumen and the apical membrane protein aquaporin-5 accumulated at the luminal cell surfaces. Moreover, laminin-5 deposition at the basal lamina region of terminal buds was accelerated in treated glands. It is suggested that hedgehog signaling promotes lumen formation and cell polarization of developing SMG epithelium.

Animals↗

Glycosidic residues in the mouse submandibular gland: biochemical determination and visualization with plant lectins.

Biochemical and histochemical studies were carried out on the mouse submandibular gland to define the presence and the localization of glycosidic residues. The results obtained by applying peanut, winged pea, wheat germ, soybean and Con A lectins to unfixed and fixed sections tallied completely with biochemical determinations of the various glycosidic residues. The data from this study have been compared with those obtained by other authors who had performed biochemical and histochemical studies on the gland; similarities and discrepancies as to the presence and the localization of the sugars are discussed.

Animals↗

Small cell undifferentiated carcinoma of the submandibular gland: immunohistochemical evidence of myoepithelial, basal and luminal cell features.

A primary small cell undifferentiated carcinoma of the submandibular gland is reported. Histological studies revealed that the major part of this tumor was composed of cells slightly larger (10-14 microm) than lymphocytes. These tumor cells showed myoepithelial-cell differentiation, which was confirmed by the immunohistochemical and ultrastructural findings. Furthermore, some of them showed luminal-cell and basal-cell differentiation immunohistochemically. However, there was no evidence of neuroendocrine differentiation. These findings demonstrated that the tumor had the features of all the salivary ductal components (myoepithelial, basal, and luminal cells) and supported that the tumor might arise from the salivary duct. Furthermore, it supports the hypothesis of multipotential stem cells as the origin for small cell undifferentiated carcinomas in salivary glands.

Actins↗

Exchange area and surface properties of the microvasculature of the rabbit submandibular gland following duct ligation.

The exchange area of the submandibular salivary gland microvasculature has been measured to allow the value of microvascular permeability (P) to hydrophilic solutes to be calculated from previous measurements of permeability-surface area (PS) products. Glands whose ducts had been ligated for 2 weeks and the contralateral control glands were perfusion-fixed with a modified Karnovsky's fixative after perfusion with a solution containing cationized ferritin, and examined with transmission electron microscopy. Stereological techniques were used to estimate the surface area of the exchange vessels on random thin sections from four control and four duct-ligated glands. The mean exchange surface area in control glands was 512 cm2 g-1 and 336 cm2 g-1 in duct-ligated glands. The fenestral density was calculated to be 0.57% of the exchange surface in control glands and 0.30% in duct-ligated tissue. Molecules of cationized ferritin appeared bound to the luminal surface of the microvascular endothelium, including the surface of the fenestrae to a depth of about 25 nm in both control and ligated glands. These experiments have shown that the exchange surface area of the fenestrated endothelium of the submandibular salivary gland is comparable to that in cardiac muscle but the permeability (P) to small solutes is about 10 times greater. Following ligation of the salivary gland duct, solute permeability falls and an explanation of this, based on the reduced surface area and the nature of the permeability-flow relationship for small solutes is offered.

Animals↗

Scanning electron microscopic observation of mouse embryonic submandibular glands during initial branching: preferential localization of fibrillar structures at the mesenchymal ridges participating in cleft formation.

Branching submandibular glands of 12-day mouse embryos and those cultured in the presence and absence of a collagenase inhibitor from the culture medium of bovine dental pulp or a Clostridial collagenase were examined with the scanning electron microscope. Fracturing of fixed and dried glands with the tip of a fine needle succeeded in exposing the surfaces of the lobules and of their mesenchymal replicas at different stages of branching. At the beginning of branching, corresponding parts of the mesenchyme formed ridges on or in which the fibrillar structures were often found. At the stage forming deeper clefts thicker fibres, 0.5-2.5 micron in diameter, were observed between two adjacent lobules. On the contrary, no apparent differences in the fibrillar structures on the epithelial surfaces were detected between the shallow cleft and noncleft regions at the initial phase of branching. These fibrillar structures were very abundant in glands cultured with collagenase inhibitor and were completely lost in glands cultured with bacterial collagenase, strongly indicating that these materials consisted of collagen. The possible involvement of mesenchyme in epithelial branching is discussed with special reference to mesenchymal traction forces that would be elicited by fibrillar collagens.

Animals↗

Intracellular Cl- activity of canine submandibular gland cells: an in vitro observation.

Intracellular Cl- activity (aiCl) and transmembrane potential (delta psi m) of canine submandibular gland cells were measured in vitro by using Cl- sensitive liquid membrane microelectrodes. Under the conditions of superfusion with a control solution, average Cl- activity of the resting cells was slightly higher than those predicted from Nernstian equilibrium.

Animals↗

Neurokinin A in the parotid and submandibular glands of the rat: immunohistochemical localization and effect on protein and peroxidase secretion.

An indirect immunofluorescence technique was used to study the distribution of neurokinin A immunoreactive (NKA-IR) nerve fibres in submandibular and parotid glands of the rat. The functional role of neurokinin A on protein and peroxidase secretion in these glands was evaluated by using in vitro methods. In the parotid gland neurokinin A immunoreactive fibres were mainly distributed around the secretory acini, but some were also in evidence around the stromal blood vessels and ducts. The number of the neurokinin A immunoreactive nerve fibres was lower in the submandibular gland than in the parotid gland. They were mainly distributed around the secretory acini and stromal blood vessels and ducts. In vitro, neurokinin A significantly stimulated the release of total amount of released proteins and peroxidase from parotid gland fragments, while in the submandibular gland only the release of peroxidase was increased. By using SDS polyacrylamide gel electrophoresis (SDS-PAGE) specific changes were found in the release of proteins after neurokinin A stimulation. The results of the present study demonstrate that neurokinin A immunoreactive nerve fibres are present in the rat parotid and submandibular glands. Their localization around the secretory elements of the glands and the effect of neurokinin A in vitro experiments indicates that neurokinin A might have a significant role in the regulation of salivary secretion.

Animals↗

Calcium dependency of adrenergic and muscarinic cholinergic stimulation of mucin release from dog submandibular gland cells.

Stimulation of muscarinic cholinergic, alpha-adrenergic and beta-adrenergic receptors elicited mucin release from dispersed dog submandibular cells. The secretory response to acetylcholine was much more pronounced than to adrenergic agonists, and largely dependent on the presence of extracellular Ca2+, but the dependency on extracellular Na+ was slight. Ionomycin also stimulated mucin release. In rat submandibular cells, neither muscarinic cholinergic agonists nor ionomycin were as effective mucosecretagogues as beta-adrenergic agonists. alpha-Adrenoceptor-mediated release was decreased by chelating extracellular Ca2+ with EGTA. The beta-adrenoceptor-mediated response was diminished by extensive exposure of cells to EGTA, due at least in part to the requirement of Ca2+ for beta-adrenoceptor stimulation of cAMP formation. 8-br-cAMP stimulated 45Ca2+ release from cells preloaded with 45Ca2+. The 8-br-cAMP-induced mucin release was eliminated in ionomycin-pretreated cells, but not inhibited by chelating extracellular Ca2+ and by the treatment of the cells with TMB-8 or in the cells loaded with BAPTA. These results suggest that not only the adrenergic system but also the muscarinic cholinergic system may participate in the regulation of mucin release in dog submandibular gland, and also provide the possibility that, in addition to a cAMP-mediated mechanism, Ca(2+)-dependent mechanisms may be involved in mucosecretion in dog submandibular acini.

8-Bromo Cyclic Adenosine Monophosphate↗

Effects of triiodothyronine on resting membrane potential of primary cultured rat submandibular gland cells.

The effect of triiodothyronine (T3) on the resting membrane potential was measured in primary cultured rat submandibular gland cells. The resting membrane potential was 29.5 +/- 0.71 mV. The hormone T3, at concentrations of 10(-9) M or greater, hyperpolarized the cells 5.8 mV (p less than 0.05). Hyperpolarization was complete within 24 hours. Ouabain (1 mM) depolarized the cells 5.9 mV. Cells exposed to T3 and ouabain had the same membrane potential as cells treated with ouabain alone. These data suggest that the hyperpolarization observed can be, in part, attributed to triiodothyronine-induced synthesis of (Na-K)-adenosine triphosphatase.

Animals↗

Effects of Ca2+ and calmodulin antagonists on the Na+ pump activity induced by pilocarpine in dog submandibular gland.

The effects of Ca2+ and calmodulin antagonists on the Na+,K+-ATPase activity were investigated in dog submandibular gland pieces. The Na+,K+-ATPase activity of the gland pieces which were incubated in the presence of 5 microM A23187, a Ca2+ ionophore, was about 2-fold of that seen in the control medium. Verapamil, diltiazem and La3+ (Ca2+ antagonists) and chlorpromazine, trifluoperazine and W-7 (calmodulin antagonists) had no significant effect on the Na+,K+-ATPase activity in the control medium, but significantly inhibited that induced by pilocarpine. These results suggest that the Na+ pump activity is modified by the Ca2+ influx from the extracellular spaces and the intracellular Ca2+-calmodulin complex.

Animals↗