Hepatic metastases in adenoid cystic carcinoma of the submandibular gland.
We present a case of adenoid cystic carcinoma of the submandibular gland resulting in metastases to the liver, nine years following initial presentation.
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We present a case of adenoid cystic carcinoma of the submandibular gland resulting in metastases to the liver, nine years following initial presentation.
BACKGROUND: Pleomorphic adenoma in the parapharyngeal space either occurs de novo or as an extension from the deep lobe of the parotid gland. CASE PRESENTATION: A rare synchronous occurrence of pleomorphic adenoma in the parapharyngeal space and submandibular gland of a 48-year-old Nigerian male is reported. CONCLUSION: Pleomorphic adenoma concurrent in the parapharyngeal space and submandibular gland is very rare. A complete surgical excision of both tumors is the treatment of choice.
1. Watery vacuolation in the acinar cells of the rat submandibular gland is described. The vacuoles are cytoplasmic, membrane-walled, and 2-20 mu in diameter. They are visible in living cells and appear to contain a watery fluid.2. Vacuolation occurred regularly in the following experimental situations: (1) in vitro-under anoxic conditions (2) post mortem-in animals killed by anoxia, and (3) in vivo-during secretion.3. By in vitro experiments it was shown that vacuolation occurs only when the cells are both anoxic and exposed to an excess of extracellular fluid containing calcium and bicarbonate. It was further shown that vacuolation is reversible in oxygen and that both its development and recovery are temperature dependent.4. Evidence is presented that the vacuolation is not a degenerative or necrotic change, that it is accompanied by the entry of fluid into the cells, and that it is not caused by simple osmosis.5. The mechanism of vacuolation and its possible relation to secretion are discussed. It is suggested that vacuolation represents an imbalance between the ingestion and secretion of water and salts.6. Similar vacuoles, apparently produced by the same mechanism, were observed in the acinar cells of the parotid gland and the pancreas of the rat.7. The close similarity of this vacuolation to that previously described in rat liver cells was noted.
OBJECTIVE: We examined the toxicity and biodistribution associated with a single administration of a first-generation, serotype 5, adenoviral vector encoding human growth hormone (hGH; AdCMVhGH) to a single rat submandibular gland in the presence of hydroxychloroquine (HCQ). Previously, we showed that hGH is primarily secreted into saliva (approximately ninefold serum level) when expressed as a transgene in salivary glands (e.g. Baum et al, 1999), but administration of HCQ substantially increases the hGH levels secreted into the bloodstream (Hoque et al, 2001). A potential application of this observation is for patients with adult hGH deficiency. METHODS: Six groups of male and female adult rats (n = 12 each) were studied, with zero to 1.5 x 10(11) particles of AdCMVhGH, +/-HCQ, administered retroductally. Multiple clinical and pathological parameters, as well as vector tissue distribution, were assessed. RESULTS: All animals survived until the scheduled day of sacrifice, and essentially no untoward events were observed clinically or at gross necropsy. We observed no vector-related effects on clinical hematology evaluations and a single, transient significant change on clinical chemistry evaluations (increased serum globulin levels). Three days after AdCMVhGH administration, the vector distributed to all tissues analyzed with the exception of gonads and heart. By day 29, most organs, other than the targeted and contralateral submandibular glands, were negative for the presence of vector. On day 3, none of the animals tested positive for the presence of replication competent adenovirus in either their blood or saliva. CONCLUSION: Salivary gland delivery of AdCMVhGH +/-HCQ appears associated with limited toxicity in rats.
Primary Sjögren Syndrome is a chronic autoimmune disease characterized by exocrine gland dysfunction. Here we present evidence of the activation of nitric oxide signaling cascade by circulating antibodies of patients with Sjögren Syndrome in rat submandibular glands. Constitutive nitric oxide synthase and cyclic GMP levels are modulated by Sjögren IgGs through the activation of muscarinic acetylcholine receptors on the glands. The effects are similar to those produced by the agonist carbachol and blocked by the antagonist atropine. The involvement of M1 subtype of muscarinic receptors is proposed since both a synthetic peptide homologous to an extracellular domain of M1 receptor and pirenzepine, a selective M1 antagonist, partially blocked the effects. We conclude that Sjögren Syndrome antibodies can activate nitric oxide signaling in submandibular glands by interacting with muscarinic acetylcholine receptors.
In an attempt to shorten tumor induction time and alter tumor anaplasticity, ductal metaplasia was induced in the submandibular gland of 30 rats by ligation of the duct and artery followed by the implanation of 4-mg pellets of pure DMBA. Control groups consisted of 19-ligated and 15-DMBA implanted rats. The ligate controls showed degeneration and atrophy of the affected gland and replacement of glandular tissue by scar tissue. The DMBA controls followed the expected pattern, with all rats eventually developing well-differentiated squamous cell carcinoma. The CMBA-ligated rats showed a combination of the two processes, each acting separately from the other. There was no difference either in induction time or tumor anaplasticity between the DMBA control rats and the DMBA-ligated rats. It seems that only factors relating to a change in the immunologic response of the host affect the latent period of tumor induction time in submandibular gland carcinogenesis.
We employed sialidase procedures followed by lectin stainings combined with oxidizing and deacetylating agents to visualize the distribution and sequentiate sialoglycoconjugates in the bovine submandibular gland. In particular we evidenced in acinar and ductal cells the dishomogeneous presence of sialic acids acetylated in the polyhydroxy side chain (C7, C8, C9), whereas O-acetyl substituents at position C1 and/or C4 were not found. Sialoglycoderivatives were also differentiated by the occurrence of penultimate sugars; indeed the dimers sialic acid-(alpha 2----3,6)-beta-galactose and sialic acid-(alpha 2----6)-alpha-N-acetylgalactosamine were identified. Using such technique we supported further the possibility to develop methods for the identification of the positions of O-acetyl groups and the reconstruction of terminal disaccharides within surface and cytoplasm glycoconjugates. in situ the distribution of different O-acylated sialoglyco-derivatives in the bovine submandibular gland. To this purpose we employed oxydizing and deacetylating agents combined with sialidase digestion and lectin binding.
An evaluation of submandibular gland secretory function was performed in young adult and aged male and female rats. No significant alterations in submandibular salivary flow rate or the concentrations of total protein, Na+,K+ and neutral sugar in the secreted saliva, were observed between different aged animals. Significant sex differences in salivary flow rate and total protein content were found.
Proteins secreted by the rat submandibular gland after administration of autonomic agonists have been fractionated by sodium dodecyl sulphate (SDS) - polyacrylamide gel electrophoresis. alpha-Adrenoceptor, beta-adrenoceptor and muscarinic agonists were all found to cause the secretion of different protein populations.
The effects of cadmium, l-arginine (nitric oxide precursor) and N(omega)-nitro-l-arginine methyl ester (l -NAME) as a nitric oxide synthesis inhibitor and cotreatment of them on rat submandibular secretory function were studied. Pure submandibular saliva was collected intraorally by micro polyethylene cannula from anaesthetized rats using pilocarpine as secretagogue. Fourteen days treatment with 10 mg l(-1)cadmium as cadmium chloride in drinking water caused significant alterations on salivary function. Salivary flow rate, total protein concentration and amylase activity of saliva were decreased while secretion of calcium was increased by cadmium. Two weeks treatment of rats with l -arginine (2.25%) in drinking water caused an increase in submandibular gland weight. Flow rate was reduced by l-NAME. The total protein concentration of saliva was increased by l-arginine while decreased by l-NAME. Calcium concentration of saliva was reduced by l-arginine and increased by l-NAME. Cotreatment of cadmium with l-arginine prevented cadmium-induced reduction of flow rate while l-NAME cotreatment potentiated cadmium-induced reduction of flow rate. l-arginine showed a preventive effect on cadmium-induced decrease of protein concentration and reached control levels. l-arginine potentiated cadmium-induced increase of saliva calcium concentration. It is confirmed that nitric oxide (NO) has a role in salivary gland function. It is also concluded that cadmium inhibitory effects on salivary gland function are modulated by the NO system as it is observed that the cadmium inhibitory effect on submandibular gland function is diminished by l-arginine and extended by l-NAME. Considering the properties of cadmium substitution for calcium in many intracellular events, different types of alterations can be discussed.
The present study concerns the effect of glucocorticoids and triiodothyronine (T3) on rat salivary (Na+ + K+)-adenosine triphosphatase (NaK-ATPase). The results indicate that corticosterone increases submandibular gland NaK-ATPase activity with a single dose of hormone and with two daily doses on three successive days. Multiple injections of dexamethasone also increases submandibular and sublingual gland NaK-ATPase activity. The effect of glucocorticoids on salivary NaK-ATPase is selective since Mg-ATPase shows no significant differences under different steroidal states. We subsequently investigate the possibility of interaction between the effects of corticosterone and triiodothyronine on submandibular gland NaK-ATPase activity. Our studies indicate that each of these hormones increases NaK-ATPase activity in the absence of the other.
The activities of chymotrypsin-like esteroproteases in the mouse submandibular gland were additively induced by 5 alpha-dihydrotestosterone (DHT) and triiodothyronine (T3). Zymograms showed that there are many isozymes whose activities are regulated by DHT and/or T3. Some isozymes seemed to be hormone-independent. Histochemical studies revealed that all these isozymes are localized in the granular convoluted tubules.
The release of mucus from acinar cells of the cat submandibular gland was examined by electron microscopy. The limiting membrane of mucous droplets fuses with the luminal plasma membrane to form a five-layered contact. This is converted to a three-layered membrane (unit membrane) by avulsion of the plasmalemma. Attenuation and rupture of this membranous barrier permits the contents of the mucous droplets to flow into the lumen.
The accessory submandibular glands in four species of bats were examined by electron microscopy. These four species represent two independently evolved lineages. The fringe-lipped bat, Trachops cirrhosis, is a Neotropical phyllostomid species, whereas the false vampire bats of southeast Asia, Megaderma lyra and M. spasma, and the heart-nosed bat, Cardioderma cor, of East Africa are megadermatid species. These glands show extreme deviation from typical salivary gland histology: their secretory endpieces are in the form of follicles and their ducts lack the cytological details that permit identification of diverse duct segments. Despite their unusual histology, the secretory endpieces in M. lyra, M. spasma, and C. cor consist of secretory cells that conform to typical secretory cell morphology. In contrast, secretion by follicular cells in T. cirrhosis involves unusual cytoplasmic bodies, and their mitochondria frequently have intracristal crystalloids. Ducts in all four species consist of simple cuboidal to columnar epithelium without basal striations. Follicles and ducts in all four bats are surrounded by numerous myoepithelial cells and are heavily innervated by hypolemmal nerve terminals. Despite their widely separated geographical ranges, all four bat species consume frogs and other vertebrates. Frogs and toads often possess toxic cutaneous glands that provide a chemical defense against predation. It is postulated that the unusual accessory glands in the four frog-eating species secrete toxin-neutralizing salivary factors. The follicular form of the endpieces permits storage of preformed saliva and their coterie of myoepithelial cells and hypolemmal nerve terminals facilitates the sudden and rapid expulsion of saliva into the oral cavity during the consumption of noxious amphibians.
Recent studies on the localization of the serine protease salivary kallikrein have led to the conclusion that it has a ductal localization and to the possibility that it is located there in small "secretory" granules. Until now, the latter inference has been based entirely on circumstantial evidence. In the present study, however, direct evidence from immunolocalization studies at the ultrastructural level establishes the localization of this enzyme in the apical duct granules in the cat submandibular gland. These granules stained only with immune sera to cat submandibular gland kallikrein and were the only subcellular structures that did so. They showed the "studded" appearance characteristic of the electron-dense aggregates of peroxidase-antiperoxidase seen in this type of immune reaction.
The effect of sialoadenectomy (submandibular gland removal) for four weeks duration was studied in five C3H mice and four sham-operated controls. This preliminary experiment using small numbers of animals indicated that sperm production parameters were lowered in sialoadenectomized animals although there were no significant differences between the sialodenectomized and sham-operated group. In a second experiment using larger numbers of animals, significant differences in testicular weights, epididymal weights, and testis weights were noted. These parameters were reduced only 10-14% from control levels. Epididymal sperm head counts were reduced 10% after sialoadenectomy but the two groups were not significantly different (P less than 0.05). No difference in testicular histology was observed. The present report contrasts to that of Tsutsumi et al. (1986) who indicate that submandibular removal with subsequent depletion of epidermal growth factor (EGF), is extremely deleterious (40-55% decreases in spermatid and sperm content) to the progress spermatogenesis.
Seasonal effects in daily beta-N-acetylglucosaminidase activity from submandibular gland of adult male mice, born and raised under rigorously controlled laboratory conditions were studied. Every four hours during one 48 h period, groups of 7 mice were killed at monthly intervals. Seasonal differences in circadian activity were found, having their acrophase at different times of the day. An attempt was made to explain the observed changes by changes in hormonal background due to a certain kind of genetic memory pertaining to laboratory animals.
Vasoactive intestinal peptide has been identified as an important regulator of submandibular salivary gland function, consistent with its localization with acetylcholine in parasympathetic neurones innervating this gland. Enzymatically dispersed acini from rat submandibular gland are a useful system in which to study gland regulation at the cellular level. Here, three aspects of vasoactive intestinal peptide interactions with acini were examined: inhibition of binding of [125I]-vasoactive intestinal peptide, stimulation of cyclic AMP production and enhancement of mucin release. Vasoactive intestinal peptide and peptide histidineisoleucineamide inhibited [125I]-vasoactive intestinal peptide binding to intact acini, with IC50 values of 16 +/- 3 and 46 +/- 17 nM, respectively. This rank order of potency agrees with that observed previously in assays using rat submandibular gland membranes and is similar to values obtained in assays measuring increases in cyclic AMP production in which the ED50 values for vasoactive intestinal peptide and peptide histidineisoleucineamide were 3.1 +/- 1.8 and 29 +/- 13 nM, respectively. Although vasoactive intestinal peptide stimulation of cyclic AMP production was only about 10% of that seen in response to isoproterenol, the levels of mucin release induced by the two agents were more similar. The ED50 for vasoactive intestinal peptide-stimulated mucin release was 0.12 +/- 0.05 nM, thus suggesting an activation anomaly in the vasoactive intestinal peptide receptor-coupled signal transduction pathway at a point between cyclic AMP production and mucin release.