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Myoepithelial neoplasia of the submandibular gland: case report and therapeutic considerations.

Tumors of the submandibular gland typically arise from the seromucinous acini, which make up the majority of the gland. The most common benign tumor of this structure is the pleomorphic adenoma, whereas the most common malignancy of the submandibular gland is adenoid cystic carcinoma. We describe an unusual case of a neoplastic process of the myoepithelial cells of the submandibular gland in a middle-aged woman. This rare tumor is most commonly diagnosed in the parotid gland and in the minor salivary glands of the hard palate; a review of the literature uncovered only 5 previous reports of myoepithelioma of the submandibular gland. Distinguishing myoepithelioma from benign pleomorphic adenoma and malignant myoepithelial carcinomas can be challenging. Immunohistochemical staining can help to distinguish between the benign neoplasms, but histologic features remain the "gold standard" for diagnosing the malignant tumors. Increasing use of immunohistochemistry panels to assess parotid neoplasms also suggests that myoepithelioma may be underrecognized.

Adenoma, Pleomorphic↗

AM1, a glycoprotein from the submandibular glands of the mouse, has esterolytic and amidolytic activities.

The previously isolated female submandibular glycoprotein AM1 ( Nieuw Amerongen , A.V., Vreugdenhil , A.P. and Roukema , P.A. (1977) Biochim. Biophys. Acta 495, 324-335) has been shown to have hydrolytic activity using N-alpha-benzoyl-L-arginine ethylester (BAEE) and ChromozymR PK as a substrate. AM1 can be secreted in vivo by isoproterenol, and to a lesser extent by carbamylcholine and phenylephrine. Based on BAEE as a substrate, AM1 has an optimum pH of 7.8. In female submandibular glands, about one-third of total esterolytic activity resided in glycoprotein AM1, but in male submandibular glands, less than 3%. The Km value of glycoprotein AM1 is 50 microM and its Vmax is 117 mumol/min per mg glycoprotein AM1. The enzymatic activity is not inhibited by Ca2+, Mg2+ and Na+, slightly by Cu2+ and strongly by Hg2+ and phenylmethylsulfonyl fluoride. Glycoprotein AM1 is capable of hydrolyzing ChromozymR PK with a turnover value 20-fold lower than that for BAEE. With ChromozymR PK as a test substrate, glycoprotein AM1 was purified by a factor of 11. With this substrate, glycoprotein AM1 has an optimum pH between 6.6 and 7.6. Also with chromozymR PK as a substrate, the submandibular glands of female mouse showed a much higher activity of glycoprotein AM1 than the submandibular glands of the male mouse. About 75% of all enzymatic activity of female submandibular glands resided in glycoprotein AM1 and in male submandibular glands 22%. The Km value is 57 microM and its Vmax 6.7 mumol/min per mg glycoprotein AM1. From the biochemical characteristics and the localization of glycoprotein AM1, it has been concluded that glycoprotein AM1 is not identical to any of the other described murine submandibular esteroproteinases , such as kallikrein, gamma-subunit of the nerve growth factor, proteinase A and proteinase F.

Amidohydrolases↗

Fructose 2,6-bisphosphate-dependent regulation of phosphofructokinase in rat submandibular gland.

1. Regulation of phosphofructokinase in rat submandibular gland was non-Michaelis-Menten type at physiological pH. 2. At pH 7.3, ATP played a dual role on phosphofructokinase acting as a substrate and inhibitor at high concentration of ATP. 3. The activator of phosphofructokinase was present in cytosol fraction, and its properties were resemble to those of fructose 2,6-bisphosphate. 4. Both the activator and authentic fructose 2,6-bisphosphate relieved the inhibition of phosphofructokinase by ATP, and increased the affinity for fructose 6-phosphate. 5. Concentration of fructose 2,6-bisphosphate in rat submandibular gland was 8.22 nmol/g tissue, and which was about the half of that in liver. 6. Phosphofructokinase in rat submandibular gland was found to be regulated synergistically by ATP, fructose 6-phosphate and fructose 2,6-bisphosphate.

Adenosine Triphosphate↗

Nitric oxide-dependent protein synthesis in parotid and submandibular glands of anaesthetized rats upon sympathetic stimulation or isoprenaline administration.

In anaesthetized female rats, the beta-adrenoceptor agonist isoprenaline was intravenously infused (20 microg kg(-1) min(-1)) for 30 min or the ascending cervical sympathetic nerve trunk was intermittently stimulated (50 Hz, 1 s every tenth second) on one side for 30 min. The incorporation of [3H]leucine into trichloroacetic acid (TCA)-insoluble material was used as an index of protein synthesis. In response to isoprenaline, the [3H]leucine incorporation increased by 79% in the parotid glands and by 82% in the submandibular glands. The neuronal type NO-synthase inhibitor N-PLA, reduced (P < 0.001) this response to 26% and 20%, respectively. Sympathetic stimulation under alpha-adrenoceptor blockade increased the [3H]leucine incorporation by 192% in the parotid glands and by 35% in the submandibular glands. N-PLA reduced the corresponding percentage figures to 86% (P < 0.01) and 8% (P < 0.05). When tested in the parotid glands, the non-selective NO-synthase inhibitor L-NAME reduced (P < 0.01) the nerve-evoked response to 91%. The increase in [3H]leucine incorporation in response to sympathetic stimulation under beta-adrenoceptor blockade was not affected by N-PLA in the parotid (139% versus 144%) and submandibular glands (39% versus 34%). In non-stimulated glands, the [3H]leucine incorporation was not influenced by the NO-synthase inhibitors. In conclusion, beta-adrenoceptor mediated salivary gland protein synthesis is largely dependent on NO generation by neuronal type NO-synthase, most likely of parenchymal origin.

Adrenergic alpha-Antagonists↗

Canine submandibular-gland hyaluronidase. Identification and subcellular distribution.

1. Submandibular glands from four species of mammal have been shown to contain a hyaluronidase active at acid pH; glands from dog and cat had a much higher content of this enzyme than has been found in other sources. 2. Product formation from hyaluronate after 24hr. incubation was almost the same as with testicular hyaluronidase, indicating that the enzyme is an endo-poly-beta-hexosaminidase. 3. When submandibular-gland homogenates were fractionated by the scheme developed for liver by de Duve, Pressman, Gianetto, Wattiaux & Appelmans (1955), all the enzymes assayed, except cytochrome c oxidase, were found to occur partly in the soluble fraction and partly in the particulate fractions. Among the particular fractions, the highest specific activity was found in the heavy-mitochondrial fraction for cytochrome c oxidase, in the microsomal fraction for alkaline phosphatase and in the light-mitochondrial fraction for acid phosphatase, beta-N-acetylhexosaminidase and acid-active hyaluronidase. 4. Release of the enzyme activity from the sedimentable fractions occurred in 0.1% Triton X-100 or after high-speed homogenization. 5. Stimulation of dogs by pilocarpine was found to decrease the hyaluronidase content of the submandibular gland by 5% and to cause the occurrence of a corresponding amount of acid-active hyaluronidase in the submandibular saliva. 6. The results are discussed in relation to the subcellular localization of hyaluronidase.

Acid Phosphatase↗

Ribonucleic acid association with androgen receptor from rat submandibular gland.

The transformed androgen receptor from rat submandibular gland converts to a faster sedimenting form (6-8S) on a glycerol gradient centrifugation after withdrawal of a transformation-inducing reagent (KCl or ATP). In this report, the association of cytosolic RNA with the transformed androgen receptor was investigated as a possible mechanism of molecular conversion of the androgen receptor. When the transformed and converted androgen receptors were treated with RNase A, these receptors sedimented at 4.5S in a low-salt glycerol gradient. Addition of RNA from rat submandibular gland to the RNase-Sepharose-treated transformed receptor caused a shift of receptor peak from 4.5S to 5.8S. RNA from rat submandibular gland, yeast RNA and E. coli rRNA inhibited DNA-cellulose binding of a RNase-treated transformed receptor in the absence of molybdate. These observations suggest that conversion from the transformed 4S androgen receptor to a 6-8S form resulted from the association of RNA(s) with the transformed receptor.

Animals↗

Chronic sialadenitis with psammoma bodies mimicking neoplasia in a fine-needle aspiration specimen from the submandibular gland.

A 65-year-old woman with a submandibular gland nodule had a fine-needle aspiration specimen that contained groups of duct-type cells and a psammoma body, suggestive of adenocarcinoma. The resected gland showed chronic sialadenitis with sialolithiasis and psammoma bodies. In a series of 81 resected nonneoplastic submandibular glands from 72 patients, psammoma bodies, nonlaminated microcalcifications, or both were found in 46 (57%). They were located most commonly just outside of striated or intercalated ducts. When examining fine-needle aspiration specimens from the submandibular gland, it is important that one be aware that psammoma bodies may occur in normal, inflamed, irradiated, and neoplastic conditions.

Adolescent↗

Purification and partial characterization of cat colon and submandibular gland kallikreins.

Kallikreins from cat colon and submandibular gland have been purified by acetone fractionation of tissue extracts, DEAE-Sephacel ion-exchange chromatography, rho-aminobenzamidine Sepharose 4B affinity chromatography and gel filtration on Sephadex G-75. They were of similar M.W., approximately 40,000, and each comprised five forms by isoelectric-focusing (pI 4.1-4.8). Both enzymes were potent kininogenases and exhibited similar specificities with synthetic ester and amide substrates. They were susceptible to a range of protease inhibitors. Surprisingly, neither was sensitive to aprotinin yet both were partially inhibited by soya-bean trypsin inhibitor. They were indistinguishable in our immunological tests. An acidic esterase (pI 2.2-3.5) of M.W. 120,000 was isolated from cat stomach by the same procedure. While it exhibited weak immunologic similarity to cat submandibular gland kallikrein, it had negligible kininogenase activity and different substrate and inhibitor specificities to the two kallikreins. It is concluded that similar tissue kallikreins are present in the colon and submandibular gland of the cat but are distinct from this cat stomach esterase.

Animals↗

Observations on two cases of apparent submandibular gland cysts in HIV positive patients: MR and CT findings.

OBJECTIVE: To present two cases of probable lymphoepithelial cysts of the submandibular glands in patients who were human immunodeficiency virus (HIV) positive and who also had lymphoepithelial cysts of the parotid glands. MATERIALS AND METHODS: Computed tomography and MRI of two HIV positive patients with lymphoepithelial cysts of the parotid glands and cysts in the submandibular glands were correlated with the histories and the possible presence of other known causes of submandibular gland multiple cysts. RESULTS: Because of the present treatment philosophy regarding HIV positive patients with major salivary gland cysts, surgical resection of these glands was not performed. All other known causes of multiple submandibular gland cysts were excluded by either history or laboratory data. CONCLUSION: Computed tomography and MRI on two patients with known HIV infection and bilateral parotid lymphoepithelial cysts are presented. Both patients also had bilateral multiple submandibular gland cysts and no evidence of obstructive glandular disease, autoimmune disease, or other organ system cysts. These cases of presumed submandibular gland lymphoepithelial cysts are rare in the literature. They are presented in the hope that other radiologists will be stimulated to document the occurrence of this entity.

Acquired Immunodeficiency Syndrome↗

Breakdown of membrane choline-phospholipids induced by endogenous and exogenous muscarinic agonist is potentiated by VIP in rat submandibular gland.

The outflow of tritium from rat submandibular gland fragments, pre-labelled with [3H]choline, following electrical or pharmacological stimulation was studied. Electrical stimulation of the tissue increased the outflow of tritium in a frequency dependent manner. Atropine treatment decreased the electrically-induced release, indicating that the outflow did not reflect acetylcholine from nerve endings, but was largely brought about by postsynaptic receptors. In agreement with this hypothesis, treatment with noradrenaline or carbachol induced a dose dependent increase in tritium outflow from the gland fragments which could be blocked by prazosin or atropine, respectively. Moreover, analysis of the tissue-associated tritium revealed an incorporation primarily in the lipid fraction of the tissue (almost 80%), of which about 90% was in phosphatidylcholine, indicating that this was the source of the tritium outflow. Pre-incubation with vasoactive intestinal polypeptide (VIP), which coexists with acetylcholine in the parasympathetic neurons innervating the submandibular gland, increased the carbachol-induced tritium overflow significantly. The effect of VIP could be imitated by the adenylyl cyclase stimulator forskolin, which increased the carbachol-stimulated tritium efflux in a dose dependent manner. Taken together, our results suggests that muscarinic- and alpha 1-receptor agonists may activate a phospholipase coupled to phosphatidylcholine hydrolysis in the rat submandibular gland. Endogenous acetylcholine released from parasympathetic nerve endings appear to activate this mechanism. Furthermore, VIP treatment, and the concomitant cAMP-accumulation, potentiates the acetylcholine induced phosphatidylcholine hydrolysis, demonstrating a new type of interaction between the classical transmitter acetylcholine and the co-stored neuropeptide VIP.

Animals↗

Persistence of a perinatal cellular phenotype in submandibular glands of adult rat.

In the perinatal submandibular gland (SMG) of the rat, Type I cells secrete protein C (89 KD) and Type III cells secrete B1-immunoreactive proteins (20-30 KD); both cell types secrete protein D (175 KD). After the disappearance of both perinatal cell types from the maturing acini, only cells of the intercalated ducts (ID) show strong reactivity for the perinatal antigens. In adult ID, light and electron microscopic immunocytochemical analysis showed that most cells had either C or B1 reactivity, a few had either C and D or B1 and D reactivities, and some cells were unreactive for all of the perinatal proteins. Occasional clusters of "adult" acini, however, were strongly positive for B1 and for D, and these clusters were negative for a typical adult acinar marker, the glutamine/glutamic acid-rich proteins (GRP). Also seen in some preparations were a few anomalous acini with the histological appearance of sublingual (SLG) acini. These were negative for the perinatal and adult submandibular gland marker proteins but reactive with an antibody against SLG mucin. We suggest that the B1-positive acini in the adult SMG consist of newly differentiated replacement cells that have arisen from the ID, and that the anomalous mucous acini are, phenotypically, SLG acini that have differentiated within the SMG parenchyma.

Animals↗

Release of kallikrein-like esterase and tonin from dispersed cells of the rat submandibular gland.

Viable dispersed cell preparations of rat submandibular gland were obtained by a tissue-dissociation procedure using collagenase and gentle mechanical force. The cells released kallikrein-like esterase in a time- and calcium-dependent manner in response to noradrenaline (10 microM) at 30 degrees C. The net loss of kallikrein-like esterase content from the dispersed cells corresponded with the increase in kallikrein-like esterase activity in the suspending medium at all concentrations of noradrenaline. These results indicate the viability and functional integrity of this dispersed cell preparation of rat submandibular gland. alpha-Adrenoceptor agonists such as noradrenaline stimulated kallikrein-like esterase and tonin release in a dose-dependent manner, whereas the beta-adrenoceptor agonist isoprenaline and cholinoceptor agonist methacoline were both inactive. Noradrenaline-induced release of kallikrein-like esterase and tonin were completely blocked by prior addition of the alpha-adrenoceptor antagonist, phenoxybenzamine. It is concluded that the secretion of kallikrein-like esterase and tonin in rat submandibular gland is mediated only via stimulation of alpha-adrenoceptors.

Adrenergic alpha-Agonists↗

Immunolocalization of anion exchanger AE2 and Na(+)-HCO(-)(3) cotransporter in rat parotid and submandibular glands.

Salivary glands secrete K(+) and HCO(-)(3) and reabsorb Na(+) and Cl(-), but the identity of transporters involved in HCO(-)(3) transport remains unclear. We investigated localization of Cl(-)/HCO(-)(3) exchanger isoform AE2 and of Na(+)-HCO(-)(3) cotransporter (NBC) in rat parotid gland (PAR) and submandibular gland (SMG) by immunoblot and immunocytochemical techniques. Immunoblotting of PAR and SMG plasma membranes with specific antibodies against mouse kidney AE2 and rat kidney NBC revealed protein bands at approximately 160 and 180 kDa for AE2 and approximately 130 kDa for NBC, as expected for the AE2 full-length protein and consistent with the apparent molecular mass of NBC in several tissues other than kidney. Immunostaining of fixed PAR and SMG tissue sections revealed specific basolateral staining of PAR acinar cells for AE2 and NBC, but in SMG acinar cells only basolateral AE2 labeling was observed. No AE2 expression was detected in any ducts. Striated, intralobular, and main duct cells of both glands showed NBC expression predominantly at basolateral membranes, with some cells being apically stained. In SMG duct cells, NBC staining exhibited a gradient of distribution from basolateral localization in more proximal parts of the ductal tree to apical localization toward distal parts of the ductal tree. Both immunoblotting signals and immunostaining were abolished in preabsorption experiments with the respective antigens. Thus the mechanisms of fluid and anion secretion in salivary acinar cells may be different between PAR and SMG, and, because NBC was detected in acinar and duct cells, it may play a more important role in transport of HCO(-)(3) by rat salivary duct cells than previously believed.

Animals↗

Giant pleomorphic adenoma of the submandibular gland. Case report.

Salivary glands are sites for a great variety of tumors. The parotid gland is the most common site followed by the submandibular gland. The pleomorphic adenoma represents the 60-70% of all tumors involving the major salivary glands, while the submandibular gland is involved in 8% of cases. The pleomorphic adenoma of the submandibular gland is rare and can present difficulty in diagnosis. The heterogeneous histology, a possible malignant transformation, an incomplete capsule that can determine a recurrence, are the most important characteristics of pleomorphic adenoma. A complete surgical removal of the tumor is the treatment of choice. In the case presented, the mass showed an unusual vascularization and remarkable dimensions.

Adenoma, Pleomorphic↗

Histology and histochemistry of the parotid and the principal and accessory submandibular glands of the little brown bat.

The parotid and the principal and accessory submandibular glands of the little brown bat. Myotis lucifugus (Vespertilionidae), were examined using light microscopy and staining methods for mucosubstances. The parotid gland is a compound tubuloacinar seromucous gland. Parotid gland secretory cells contain both neutral and nonsulfated acidic mucosubstances. The principal and accessory submandibular glands are compound tubuloacinar mucus-secreting glands. They contain somewhat atypical mucus-secreting demilunar cells that often appear to be interspersed between mucous tubule cells. The mucous tubule cells in both the principal and accessory submandibular glands contain sulfonmucins. Demilunar cells of the principal submandibular gland contain moderate amounts of nonsulfated acidic mucosubstances, but the corresponding cells of the accessory submandibular gland contain considerable neutral mucosubstance with very little acid mucosubstance. Intercalated ducts composed of cuboidal or low columnar epithelial cells are present in all three glands. Striated ducts in all glands are composed of columnar cells whose apices bulge into the ductal lumina. Excretory ducts are composed of simple columnar epithelium, with occasional basal cells that suggest a possible pseudostratified nature. The cells of the excretory ducts also have bulging apices. All duct types contain apical cytoplasmic secretory material that is a periodic acid-Schiff positive, neutral mucosubstance. Ductal apical secretory material is more evident in intercalated and striated ducts than in excretory ducts.

Animals↗

Gustatory sweating syndrome of the submandibular gland.

Gustatory sweating syndrome involving the submandibular gland is rare. We present a case of a patient who experienced this syndrome 5 years after undergoing submandibular gland resection. Our patient was satisfied simply with an explanation of the disorder and reassurance. But in cases where further intervention is sought, medical and surgical options are available and should be individualized for the patient.

Adolescent↗

[Immunofluorescent and immunoenzymatic analysis of an insulin-like protein of the mouse submandibular glands using monoclonal antibodies to insulin].

As has been reported earlier, submandibular glands of animals and man contain insulin-like protein (ILP), similar in some of its properties to pancreatic insulin. An immunocytochemical method with polyclonal anti-insulin serum has shown that ILP is contained in cells of the submandibular gland granular ducts. This paper is concerned with the determination of localization of ILP and estimation of its structural identity with insulin by using monoclonal antibodies to pig insulin. ILP and insulin were extracted from mouse submandibular glands and pancreas and partially purified. Solid-phase immunoenzymatic analysis was used to determine the capacity of mouse ILP and pancreatic insulin to bind specifically with monoclonal antibodies to pig insulin indicating the structural identity of ILP and insulin. The absence of cross-reaction of antibodies with the nerve growth factor and kallikrein (biologically active substances contained in the submandibular gland granular ducts) was established. An immunofluorescent indirect method with the use of monoclonal antibodies to insulin has shown that ILP is localized in cells of the submandibular gland granular ducts. It confirms the previously reported results.

Animals↗

Calcitonin gene-related peptide (CGRP) and its effects on protein release in vitro in the developing submandibular gland of the rat.

Indirect immunohistochemical methods were used to study presence and number of CGRP-immunoreactive (CGRP-IR) nerve fibers in the submandibular gland and ganglion cells of the superior cervical, submandibular and trigeminal ganglia of the developing rat. The effect of CGRP on peroxidase and total protein release was also studied in the developing postnatal submandibular glands of 1, 5, 12 and 30-day-old, as well as adult rats by in vitro methods. The possible costimulation of CGRP with SP, NKA or carbachol on 5-day-old and adult rats was also tested. The stimulatory effects of these compounds were compared to the basic release of peroxidase and total amount of proteins from submandibular gland fragments in incubation solution. CGRP-IR nerve fibers were found in relatively high number during post-natal development, mainly around blood vessels and ducts. Some CGRP-IR nerve fibers were also detected around acini. The number of these fibers was quite low and remained constant during the post-natal development. The number of CGRP-IR trigeminal ganglion cells was higher on the 5th and 12th post-natal day than later in development and in adult animals. At the same time, superior cervical- and submandibular ganglion cells were non-reactive for CGRP, suggesting trigeminal origin of CGRP-IR nerve fibers during the development in the submandibular gland. In the secretory studies, CGRP per se stimulated both peroxidase and total protein release in the submandibular gland most effectively on 5th and 12th post-natal days, while there was no clear secretory response in the adult glands. In the 5-day-old submandibular gland CGRP in combination with SP, NKA or carbachol clearly enhanced the total protein secretory response when compared with the release caused by these substances alone. However, in the adult submandibular gland, the combinations did not enhance total protein release more than any of the substances alone. Furthermore, it can be concluded that the presence of a more dense CGRP-IR innervation during the early postnatal period in the developing submandibular gland is accompanied with an increased responsiveness of the secretory elements to CGRP.

Aging↗