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Malignant submandibular gland tumors. A review of 91 patients.

A retrospective review of 91 patients with submandibular gland carcinoma seen between 1958 and 1984, is reported. Among these were 37 (41%) adenoidcystic carcinomas, 14 (15%) adenocarcinomas, 14 (15%) mucoepidermoid carcinomas, and 10 (11%) malignant mixed tumors. The median patient age was 58 (26-93) [corrected] years and the male to female ratio was was 1.2:1. At diagnosis, 15 (16.5%) patients had regional metastases and six (7%) had distant metastases. The first planned treatment was surgery in 30 (33%) patients, radiotherapy in five (5%), and surgery and radiotherapy combined in 54 (59%) patients. The 5- and 10-year cause-specific survival rates were 60 and 48%, respectively, and the relapse-free rates 42 and 34%. The locoregional control at 5 years was 30% when surgery was the only treatment, and 69% when combined with radiation. These results suggest the advantages of combining surgery and radiotherapy as the first planned treatment for most tumors.

Adult↗

[Identification of DNA synthesis stimulating and inhibitory factors from the rat submandibular gland during post-natal differentiation (author's transl)].

Cell-free homogenates of submandibular gland of 10 to 90 days old female rats, when injected in 90 days old female rats, previously treated with isoproterenol, produced a stimulatory or an inhibitory effect on the DNA synthesis. By filtration on Sephadex G-100 it was possible to separate protein or proteins presenting such an effects. The stimulatory effect was found in glands of 10 to 30 days old rats, while the inhibitory one was present in the 60 to 90 days old rats. It seems that there is a coincidence between the appearance of acinar cells and the presence of the inhibitory factor.

Animals↗

Muscarinic, alpha 1-adrenergic and peptidergic agonists stimulate phosphoinositide hydrolysis and regulate mucin secretion in rat submandibular gland cells.

Three classes of agonists associated with Ca2+-mobilization--alpha 1-adrenergic (methoxamine), muscarinic (carbachol) and peptidergic (substance P, SP)--significantly stimulated the secretion of mucin from enzymatically-dispersed rat submandibular gland acinar cells. The same three secretagogues also caused the hydrolysis of membrane inositol phospholipids, resulting in elevated cellular levels of inositol phosphates, particularly inositol 1,4,5-trisphosphate (IP3). Exogenous IP3 elicited the dose-dependent release of mucin in dispersed cells suggesting that agonist-generated endogenous IP3 may provoke a secretory response. IP3 and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination, stimulated an additive secretion of mucin in the model. The potential use of these two agents as specific probes of the IP3- and diacylglycerol-associated legs of the polyphosphoinositide (PPI) breakdown pathway is indicated. Although all three agonists shared a common action in stimulating PPI hydrolysis, their effects on the beta-adrenergic mucosecretory response were inconsistent. A brief preincubation of cells with carbachol or SP significantly reduced the subsequent isoproterenol (IPR)-provoked secretion of mucin, whereas methoxamine plus IPR stimulated an additive response. The mechanisms underlying these opposite effects are not known. Failure of IP3 or TPA to modify IPR responses suggests that modulation of the beta response may operate at a locus before the generation of diacylglycerol and IP3, possibly at the level of signal transduction. The study indicates a role for Ca2+-mobilizing agonists in controlling submandibular mucin secretion and provides evidence that receptor-linked phosphoinositide hydrolysis is an early stage in their stimulus-secretion coupling mechanism.

Animals↗

[Dielectric behavior of isolated rat submandibular glands: simulation with a vesicle-inclusion cell model].

In an attempt to correlate the passive electrical properties of the secretory tissue with its structure, I measured AC admittances for isolated rat submandibular glands, over the frequency range between 100 Hz and 500 MHz. Animals were divided into three groups: control and treatment with two different secretagogues, isoproterenol and pilocarpine. Dielectric dispersions observed from control glands had two characteristic frequencies at 2.6 kHz and 59 kHz; the former was of the alpha-type and the latter of the beta-type. Secretagogue-stimulated glands exhibited broader beta-dispersion curves. These dispersion data were analysed on the basis of a "two-shell model" with vesicle inclusions, in which two concentric shells represent the cell membrane and the nuclear envelope, and membrane-bounded vesicles are meant for secretory granules dispersed in the inter-shell space. Simulation by this model generated a good fit to data from the three groups. The analyses revealed that: (i) electric capacities for the cell and granular membranes were 2.1 and 0.9 microF/cm2, respectively; (ii) the conductivity of extracellular matrix was close to that of blood plasma; (iii) the conductivity ratio between cytoplasm and extracellular matrix was approx. 0.4; and (iv) the conductivity ratio between intragranular space and cytoplasm was approx. 0.7.

Animals↗

[Effect of proton pump inhibitor, in combination with epidermal growth factor, on the healing of chronic gastric ulcer in submandibular gland removed rats].

The effect of a proton pump inhibitor, omeprazole (OPZ), in combination with mouse epidermal growth factor (EGF), on the healing of chronic gastric ulcers induced by acetic acid in submandibular glands removed rats (SMR rat) was investigated. Four separate groups of SMR rats were orally administered 1 ml of distilled water (control), 100 mg/kg of OPZ alone (OPZ), 5 micrograms/kg of mouse EGF alone (EGF), or combination with (EGF + OPZ) twice daily. Two weeks later, ulcer areas of four groups were measured and expressed as the ulcer index (UI). The UI of the OPZ and EGF + OPZ group was significantly reduced as compared with that of the control. Furthermore, the UI of the EGF + OPZ group was significantly smaller than that of the EGF group. The present study indicates that the proton pump inhibitor promotes healing of chronic gastric ulcers in SMR rats and the effect of the proton pump inhibitor is enhanced by administration of mouse EGF.

Acetates↗

MUC4 is a major component of salivary mucin MG1 secreted by the human submandibular gland.

High molecular weight salivary mucin (MG1) is an important component of saliva, contributing to the lubricative and tissue-protective functions of this biological fluid. We have shown previously that the human mucin gene MUC5B is expressed at high levels in sublingual gland and is a significant constituent of MG1. Since many epithelia express multiple mucin genes, it seemed likely that MG1 in salivary secretions is also a heterogeneous mixture of mucin gene products. The aim of this study was to determine whether MUC4, a mucin shown in Northern blotting experiments to be expressed in salivary glands, was a significant protein component of MG1 in salivary secretions. Two cDNA clones containing MUC4 tandem repeats were isolated from a human submandibular gland cDNA library. In addition, recombinant MUC4 produced in a bacterial expression system cross-reacted with an antibody directed against deglycosylated MG1. This shows conclusively that human salivary mucin MG1 contains both MUC5B and MUC4 gene products suggesting that each mucin may perform distinct functions in the oral cavity.

Amino Acid Sequence↗

Studies on the salivary secretion induced by substance P in perfused submandibular gland of rat.

The purpose of these experiments was to clarify the effects of substance P (SP) on the salivary secretion in comparison with those of autonomic agents. Salivary secretion from rat submandibular gland (SMG) was induced by intravenous infusion into the femoral vein or partial perfusion of SMG with isotonic solution containing SP or autonomic stimulants. Blood and salivary flow rates, and electrolyte concentrations of saliva were measured. The relationship between electrolyte concentrations and salivary flow rate after intravenous infusion of SP was similar to that obtained using parasympathomimetic agents. Salivary flow rates induced by phenylephrine and isoproterenol were significantly increased by the further addition of SP, while the pilocarpine-induced flow rate was not affected. SP alone caused a significant increase in blood flow rate of perfused rat SMG. SP with atropine or phentolamine somewhat increased the blood flow. However, concomitant perfusion of atropine and phentolamine completely inhibited the SP effect. Salivary secretion induced by SP perfusion was reduced by atropine or phentolamine. Both blood flow elevation and salivary secretion induced by SP were reduced with increasing doses of a SP-antagonist. Also blood and salivary flow responses induced by phenylephrine were severely reduced by the SP-antagonist. On the other hand, the salivary secretion induced by pilocarpine was moderately reduced by the SP-antagonist. These results indicate that the salivation and especially the glandular vasodilation induced by SP were partially modified by the autonomic agents.

Animals↗

Substructures of the acinar basement membrane of rat submandibular gland as shown by alcian blue staining and cryo-fixation followed by freeze-substitution.

The ultrastructure of the epithelial basement membrane was studied in the acinar cells of adult rat submandibular glands after: (i) immersion fixation in 0.1 M sodium cacodylate buffer (CB, pH 7.2) containing 2.5% glutaraldehyde (GA) and alcian blue (0.5%) in conjunction with microwave irradiation, (ii) perfusion fixation with 2.5% GA in CB, (iii) rapid freezing followed by freeze-substitution (RF-FS) with 1% GA in acetone, and (iv) RF-FS with 2% OsO4 in acetone. The specimens were post-fixed with 1% OsO4 in CB after methods (i) and (ii) but not (iii) and (iv). Fixed specimens were embedded in epoxy resin and the ultrathin sections were cut, stained with both lead and uranium, and observed under a transmission electron microscope. Various substructural components could be seen in the acinar basement membrane. In the specimens processed by method (iv), a clear meshwork structure could be found just beneath the basal plasma membrane. This meshwork could not be seen in the specimens processed by method (iii) but thin filaments of approximately 100 nm in length extending from the epithelial base toward the connective tissue space were evident. By methods (i) and (ii), an electron dense 30-75 nm layer could be seen subjacent to basal cell membranes. By method (ii), particularly, thick threads connecting this layer to collagen fibres in the connective tissue were stained with alcian blue. Lamina lucida was not identified.

Alcian Blue↗

The vasodilator and secretory effects elicited by sympathetic nerve stimulation in cat submandibular gland.

The effects of electrical stimulation of the peripheral cut ends of the ascending cervical sympathetic trunk on vasomotor, particularly vasodilator, response were studied in relation to salivary secretion in the cat submandibular gland. The vasodilator and salivary responses were compared by stimulating the peripheral cut ends of the sympathetic nerve at various intensities (1-8 V), durations (5-60 s) and frequencies (1-100 Hz) using a 2 ms pulse duration. Electrical stimulation of the cervical sympathetic nerves caused vasoconstriction followed by vasodilatation and salivation. There were certain differences in the maximal responses of vasodilatation and salivation during sympathetic stimulation. For example, optimal frequencies for vasodilatation and salivation were 10 Hz and 20 Hz, respectively. Time-dependent increases in vasodilatation and salivary secretion were seen for periods of up to 30 s and 60 s, respectively. The volume of salivation was not necessarily correlated with the magnitude of vasodilator response. Prior treatment with an alpha-adrenoceptor blocking agent phentolamine largely reduced vasoconstriction (P < 0.01) and almost completely abolished salivary secretion (P < 0.01), but had only a slight inhibitory effect on vasodilatation (0.1 < P < 0.05). Propranolol (a beta-adrenoceptor blocking agent) pretreatment significantly decreased vasodilatation (P < 0.05) but had no statistically significant effect on vasoconstriction or salivation. Scopolamine (a muscarinic cholinoceptor blocking agent) had no effect on the responses followed by sympathetic nerve stimulation but abolished the vagal mediated reflex salivation, indicating that the salivation, but not vasodilatation, elicited by activation of the afferent fibers of the vagus nerve is mediated via parasympathetic muscarinic fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗

Effects of chemical sympathectomy on postnatal development of the rat submandibular gland.

Temporary chemical sympathectomy was accomplished by daily injection of the catecholamine-depleting agent, reserpine, for the first six days of life. The rat pups were then allowed to mature, and their submandibular glands (SMG) sequentially examined by light and electron microscopy. Reserpine retarded SMG development by about two weeks when compared to saline-treated litter-mates. One day after the end of reserpine treatment, glands appeared rudimentary, similar to those of newborns. With age the glands matured, and seven weeks after treatment (eight weeks of age), there were few structural differences between glands from experimental or control animals. In a separate experiment, 12 newborn rats were treated with reserpine for six days and then allowed to mature to 12 weeks. Three developed an obstructive sialadenitis. Several experiments were run to see if this lesion could be replicated. Only three of 36 more animals developed sialadenitis, so its induction was neither consistent nor reproducible.

Animals↗

Frey's syndrome following submandibular gland excision: an unusual postoperative complication.

Gustatory sweating and flushing, or Frey's syndrome, is a fairly common complication following surgery or injury to the parotid gland and is thought to be caused by aberrant nerve regeneration. A similar condition has been reported in the literature following surgery to the submandibular region. Since this was first described in 1934, only 7 subsequent cases of submandibular sweating and flushing have been reported. We present a case of a 52-year-old female who underwent excision of the left submandibular gland as a result of chronic sialadenitis. Twelve months following surgery, symptoms indicative of Frey's syndrome were experienced in the operative region. A review of the aetiology and treatment of the condition is described.

Female↗

Plasminogen activator activity in the subunits of mouse submandibular gland nerve-growth factor and epidermal growth factor.

The 7S nerve-growth factor (7S NGF), high molecular weight epidermal growth factor (HMW-EGF) and their subunits were isolated from mouse submandibular gland. Plasminogen activator activity was found in the 7S NGF and HMW-EGF, as well as in the gamma subunit and EGF-binding protein. Later activities were two- or three-fold higher than those of original growth factors. The alpha subunit, beta subunit and low molecular weight EGF showed no activity. The gamma 1, gamma 2 and gamma 3 subunits of 7S NGF showed plasminogen activator activity almost equal to that of the original gamma subunit.

Animals↗

Beta-adrenoceptor changes in submandibular glands of old mice.

The hypothesis that modifications in beta-adrenergic receptors may be responsible for age-dependent change previously observed in vivo, has been investigated. Beta-adrenoceptor characteristics of submandibular glands of mice were studied by using the beta-adrenergic antagonist (-)-[3H]dihydroalprenolol. Data from such studies indicated the presence of two functional populations of binding sites in membrane preparations from young animals, displaying high and low affinity, respectively. Experiments performed on old mice membrane preparations revealed a 50% decrease in the high-affinity population receptor number when compared to the preparations from young animals. However, the affinity did not change significantly with advancing age. With regard to the low-affinity population, no statistically significant changes were observed. From these data it can be reasonably assumed that beta-adrenoceptor alteration during ageing may play a major role in the age-dependent impairment of beta-adrenergic responses in vivo.

Aging↗

Actinomycosis of submandibular gland: an unusual presentation.

An unusual presentation of oro-facial actinomycosis, mimicking the clinical appearance of a malignant lesion is reported. The patient, a 74-year-old female, presented with a right submandibular mass, which slowly grew in size over a period of about 2 months, and a modest dysphagia. A painless cervical mass was palpable over the submandibular region. The rhino-pharyngo-laryngeal region, explored by flexible fiberoptic examination, was normal. At ultrasonography, a 2x2 cm infiltrating dyshomogeneous mass, involving the right submandibular gland, was visible. No connection with adjacent organs was found. There was no associated cervical lymphoadenopathy. Ultrasound-guided fine-needle aspiration cytology, performed on lesion, revealed no evidence of malignancy. The presence of characteristic colonies of actinomyces infection was found. The patient was treated initially with tetracycline chloridrate 100 mg: 1 tablet every 12 hours for 7 weeks, but a repeat ultrasonography showed no resolution. A further fine-needle aspiration cytology showed no actinomyces infection in the specimen. The patient was treated with methylprednisolone, 20 mg every 24 hours, for 5 days. After steroid treatment, the patient has been well and, upon repeat ultrasonography, total resolution of the submandibular lesion was confirmed. In conclusion, the clinical presentation of cervicofacial actinomycosis is variable and may mimic a malignant lesion or chronic granulomatous infections. Diagnostic and therapeutic findings are discussed.

Actinomycosis↗

A comparative study of the effects of four choline esters on the secretion of fluid and glycoprotein from rat submandibular glands.

The actions of four choline esters, acetylcholine (ACH), methacholine (MET), carbachol (CAR) and bethanechol (BET), on the secretion of saliva and the specific glycoprotein (GP) contained in the secretory cells of the submandibular gland (SMG) of the rat were compared under conditions with and without physostigmine (PHY). The ED50 values with respect to salivation were 17 mg/kg for ACH, 1060 micrograms/kg for BET, 810 micrograms/kg for MET and 75 micrograms/kg for CAR, whereas after pretreatment with PHY, ED50 values were lowered to 7.5 mg/kg for ACH and 212 micrograms/kg for MET, but remained unchanged for CAR and BET. SDS-polyacrylamide gel electrophoresis demonstrated that the saliva from the SMG elicited by the four choline esters contained GP I (130 KDa) and GP IV (21.5 KDa), characteristic of the acinus, and a band of GP III (31 KDa), which originates from the granular tubules. The order of intensity of these bands was band I much greater than band III = band IV. Among these bands, band I increased in intensity in a dose-dependent manner. These results suggest that the four choline esters act mainly on the acinar cells, but exert some effects on the granular tubules of the rat SMG.

Acetylcholine↗

Parasympathetic-mediated reflex salivation and vasodilatation in the cat submandibular gland.

The aim of the present study was to compare and characterize the secretory and vasodilator effects induced by chorda lingual nerve (CLN) stimulation (i.e., direct parasympathetic stimulation) and reflex parasympathetic stimulation in the submandibular gland (SMG) of sympathectomized cats. The increase in blood flow and salivary secretion in response to electrical stimulation of the central cut ends of the vagus and inferior alveolar nerves, as well as to stimulation of the CLN at a site approximately 5 mm distal to the intersection of the CLN and the SMG duct (site D) was completely abolished by section of the chorda tympani nerve (CTN). Neither response to CLN stimulation at a site nearly 5 mm proximal to the intersection of the CLN and the SMG duct (site C) was affected by CTN section. Section of the CLN at a site approximately 5 mm distal to the intersection of the CTN and the CLN abolished the submandibular salivary and vasodilator responses elicited by CLN stimulation at site D but had no effect on the two responses evoked by CLN stimulation at site C. The blood flow increases evoked by electrical stimulation of the CLN at site D were greatly reduced by prior treatment with the autonomic ganglion blocker hexamethonium, but the vasodilator responses evoked from site C were reduced much less. These data suggest that the secretory and vasodilator responses elicited by CLN stimulation at site D and those by vagus and inferior alveolar nerve stimulation are mediated largely via a parasympathetic reflex mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗