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PubMed1979

[On the ultrastructure of the parotid and submandibular gland of the mongoose Herpestes edwardsi (Viverridae) (author's transl)].

The parotid and submandibular glands of the mongoose are described. Essential differences between the 2 glands were recognized in the acini; however, the intra- and interlobular ducts are built up similarly. The parotid gland is acinar. Its secretory cells are filled with distinct types of granula, which show a considerable variation of size and structure of their secretory material. Organelles are found sparsely. The submandibular gland, however, is tubuloacinar. Its tubuli are capped with cells which belong to the demilunes of v. EBNER, but because of their pale granules they occupy an exceptional position. As the acinar cells of the parotid gland, they form intercellular canaliculi by their plasmalemmata. In the secretory cells of the tubules an intimate contact between the rER and the granules is observed. The intralobular duct surface is built up by an onelayered epithelial cell formation. The cytoplasm of the intercalated duct cells is rich in bundles of filaments, and these cells contain mitochondria with a particular dense matrix. Some microvilli cover the apical surface. In the cells of the striated ducts several populations of granules differing in size and electron density are found. The material of the dense granules shows a marginal plate-like condensation, sometimes it cristallizes. It is supposed that they were released by an apocrine extrusion mechanism. Terminal axons innervate the acini, the duct cells, and also the myoepithelial cells. The findings are compared with the well-known morphology of the salivary glands of the cat.

Animals↗
PubMed1999

Radiation-induced progressive decrease in fluid secretion in rat submandibular glands is related to decreased acinar volume and not impaired calcium signaling.

The mechanism(s) of radiation-induced salivary gland dysfunction is poorly understood. In the present study, we have assessed the secretory function (muscarinic agonist-stimulated saliva flow, intracellular calcium mobilization, Na+/K+/2Cl- cotransport activity) in rat submandibular glands 12 months postirradiation (single dose, 10 Gy). The morphological status of glands from control and irradiated rats was also determined. Pilocarpine-stimulated salivary flow was decreased by 67% at 12 months (but not at 3 months) after irradiation. This was associated with a 47% decrease in the wet weight of the irradiated glands. Histological and morphometric analysis demonstrated that acinar cells were smaller and occupied relatively less volume and convoluted granular tubules were smaller but occupied the same relative volume, while intercalated and striated ducts maintained their size but occupied a greater relative volume in submandibular glands from irradiated compared to control animals. In addition, no inflammation or fibrosis was observed in the irradiated tissues. Carbachol- or thapsigargin-stimulated mobilization of Ca2+ was similar in dispersed submandibular gland cells from control and irradiated animals. Further, [Ca2+]i imaging of individual ducts and acini from control and irradiated groups showed, for the first time, that mobilization of Ca2+ in either cell type was not altered by the radiation treatment. The carbachol-stimulated, bumetanide-sensitive component of the Na+/K+/ 2Cl- cotransport activity was also similar in submandibular gland cells from control and irradiated animals. These data demonstrate that a single dose of gamma radiation induces a progressive loss of submandibular gland tissue and function. This loss of salivary flow is not due to chronic inflammation or fibrosis of the gland or an alteration in the neurotransmitter signaling mechanism in the acinar or ductal cells. The radiation-induced decrease in fluid secretion appears to be related to a change in either the water-handling capacity of the acini or the number of acinar cells in the gland.

Animals↗
PubMed2005

[Salivary duct carcinoma of the submandibular gland].

BACKGROUND: Salivary duct carcinoma (SDC) is a rare adenocarcinoma of the salivary glands which usually occurs in the parotid gland (approx. 80%), but is also found in the submandibular gland (approx. 12%) and the minor salivary glands. Due to the low incidence of this tumour-particularly in terms of involvement of the submandibular and minor salivary glands-only limited clinical data is available. PATIENTS/METHOD: In a retrospective investigation, follow-ups of six patients with a SDC of the submandibular gland were analysed and the surgical measures evaluated for their efficiency. RESULTS: At the time of diagnosis, varying tumor stages were present (2xT1, 3xT2, 1xT1). Initial lymph node metastasis was observed in four (66.6%) of the six patients. In all patients, the submandibular gland was resected and neck dissection performed, in two cases (33,3%) this was followed by radiotherapy. Four patients developed a life-threatening local recurrence. Only one patient developed distant metastasis. Two thirds of the patients died due to tumor-related disease after an average of 35.5 months. CONCLUSION: The clinical course of patients with SDC of the submandibular gland exhibits a high (66.6%) rate of local recurrence, crucial for the following clinical course. The treatment of these patients, therefore, must include radical tumor resection as well as tissue resection with a wide margin.

Adenocarcinoma↗
PubMed1993

Regeneration of the intralobular duct and acinus in rat submandibular glands after YAG laser irradiation.

The present study was performed to understand the regeneration of the intralobular duct and acinus of partially injured salivary glands. Sections of rat submandibular glands irradiated with YAG laser were investigated histologically, and the proliferative activity of regenerating tissue was also investigated immunohistochemically with anti 5-bromo-2'-deoxyuridine (BrdU) monoclonal antibody. After YAG laser irradiation, duct-like structures continuous to the remaining ducts were regenerated at the periphery of the injured lobule. At the distal end of the duct-like structures, squamous cells were shown to form epithelial clusters. Additionally, immature acinar cells appeared budding off from the duct-like structures. During regeneration, BrdU-positive cells were observed in these duct-like structures, epithelial clusters, and immature acini. This study showed that duct-like structures, epithelial clusters and immature acini appear during the regeneration process of partially injured lobules, and that each structure proliferated in order to contribute to the rapid regeneration of the salivary gland.

Animals↗
PubMed2004

Endoscopic neck surgery: resection of the submandibular gland in a cadaver model.

OBJECTIVES/HYPOTHESIS: The objective was to evaluate the feasibility of performing a totally endoscopic resection of the submandibular gland in a cadaver model. STUDY DESIGN: Prospective, nonrandomized experimental investigation in a cadaver model. METHODS: A modified endoscopic surgical approach (representing a hybrid of balloon dissection and low-pressure carbon dioxide insufflation) previously developed in a porcine model was implemented in fresh cadavers. Once a reliable protocol was achieved, eight procedures were performed in six cadavers. Data collected prospectively included the operative time, inadvertent neurovascular injury, and size of the glands. RESULTS: All eight endoscopic submandibular gland resections were successfully performed in six consecutive cadavers (no conversions to open resection were necessary). The duration of the procedures ranged from 50 to 150 minutes, with a median duration of 65.5 minutes and a steady trend toward a shorter duration. Histological examination confirmed the presence of normal glandular architecture without evidence of excessive trauma or thermal injury. The optimal spacing of the instrument ports was 4 cm from the camera port. There were no cases of neurovascular injury. In two cadavers, a minimal amount of subcutaneous emphysema could be appreciated, which was limited to the skin overlying the dissection. CONCLUSION: Totally endoscopic resection of the submandibular gland is possible by combining balloon dissection with low-pressure carbon dioxide insufflation. The excellent visualization afforded by the endoscope provided a safe operative approach. Ultimately, a number of endoscopic neck procedures may be possible, and clinical trials are under way.

Cadaver↗
PubMed2005

Lymphocyte subsets in irradiation-induced sialadenitis of the submandibular gland.

AIMS: Irradiation-induced sialadenitis is a significant cause of morbidity in head and neck cancer patients receiving radiotherapy. Neither the exact aetiopathology of chronic irradiation-induced sialadenitis nor the mechanisms leading to atrophy of the glandular cells associated with an increase in extracellular matrix are understood. The aim of our study was to determine the phenotype of the inflammatory infiltrate and to study its distribution in the affected submandibular glands. METHODS AND RESULTS: Paraffin-embedded submandibular glands from a homogeneous group of 19 patients with advanced oropharyngeal cancer who received conventional radiotherapy to the primary site and upper neck were analysed. In all patients the radiation dose and field were approximately equal. The submandibular glands were obtained during neck dissection. To characterize the lymphoid infiltrate, all tissue sections were immunostained for T cells (CD3, CD4, CD8), cytotoxic T cells (granzyme B), B cells (CD20), and macrophages (Ki-M1p). A histopathological classification into four grades was established based on the degree of glandular atrophy, fibrosis and lymphocytic infiltration. Phenotypic analysis of submandibular gland sections revealed that the great majority of lymphocytic infiltrates were cytotoxic T cells associated with acinar cell destruction. CONCLUSIONS: The significantly elevated frequencies of cytotoxic cells in the submandibular glands of patients with irradiation-induced sialadenitis suggest that cell-mediated immune mechanisms may play a part in the pathogenesis of this disease.

Adult↗
PubMed1981

Immunocytochemical investigations on the submandibular glands of developing and adult mice using a specific antiserum on protease A.

The submandibular glands of developing and adult mice were studied immunocytochemically by the unlabeled antibody peroxidase-antiperoxidase and the colloidal gold-protein A methods, using an antiserum to a highly purified esteroprotease (protease A, EC 3.4.4) of mouse submandibular gland origin. A thin subluminal rim of immunoreactivity, seen in striated duct cells throughout development, persisted in adulthood. From 15 days of age onwards, striated duct cells with diffuse cytoplasmic staining also occurred; such cells increased in number with age. A clear sexual dimorphism of the submandibular gland was first discernable by 25 days of age, when the developing granular convoluted tubule (GCT) cells of males were slightly larger than those of females; this size difference became more pronounced at later ages, resulting in a distinct dimorphism by 50 days of age. In adults, the principal sites of immunoreactivity were the GCTs, whose component cells stained with different intensities. Electron microscopic immunocytochemical techniques revealed that deposits of oxidized diaminobenzidine or particles of celloidal gold were restricted to the secretion granules of GCT cells; all other organelles were unstained. Acinar and intercalcated duct cells were negative.

Animals↗
PubMed1986

Effect of x-ray irradiation on lipid peroxide levels in the rat submandibular gland.

We examined the effect of local x-ray irradiation on the changes in the lipid peroxide level in submandibular gland, liver, and blood plasma. Rats five weeks of age received a single low dose of 3 Gy x-ray irradiation to their neck regions. The lipid peroxide level in the submandibular gland was significantly enhanced at seven days after irradiation, as was the level in the blood plasma at two hours, seven and 14 days after irradiation. The lipid peroxide level in the liver decreased, as compared with levels in the controls. There was a slight tendency for acinar cells of the submandibular gland to show pyknosis and anomalous nuclei within three days after irradiation. These results suggest that radiation injury results in an elevation of the lipid peroxides in the submandibular gland, and an increased level in the blood.

Animals↗
PubMedDate not supplied

Small-cell undifferentiated carcinoma of the submandibular gland: an extremely rare extrapulmonary site.

The occurrence of small-cell undifferentiated carcinoma (SCUC) has seldom been reported in the submandibular gland. A primary SCUC with immunoreactivity for neuron-specific enolase and chromogranin-A antibodies was reported in the submandibular gland of a 39-year-old man. The patient received primary tumor excision and adjuvant chemotherapy with 6 courses of cisplatin and etoposide. The patient remained free of symptoms for 12 months after treatment. Submandibular gland is an extremely rare site of extrapulmonary SCUC. Primary tumor excision and adjuvant chemotherapy with cisplatin and etoposide could be a viable option. The clinicopathologic features, differential diagnoses, and the nature of the disease are discussed.

Adult↗
PubMed2002

Comparison of radiosensitivity of rat parotid and submandibular glands after different radiation schedules.

BACKGROUND AND PURPOSE: To investigate the radiosensitivity of rat parotid and submandibular gland functioning after local single dose, conventional fractionated and accelerated fractionated irradiation. METHODS: The salivary glands of male albino Wistar rats were locally irradiated with a single dose (15 Gy) or a calculated (alpha/beta; 9.6) biological effective dose of fractionated irradiation equal to this, viz. conventional fractionation (32 Gy in 16 fractions of 2 Gy/day, five times/week) or accelerated fractionation (32 Gy in 16 fractions of 2 Gy, two fractions/day). Parotid and submandibular/sublingual saliva samples were collected by means of miniaturized Lashley cups before and up to 240 days after irradiation. Salivary flow rate, lag phase and amylase secretion were used as parameters for the assessment of salivary gland function. At the end of the experiments the animals were sacrificed and the glands processed for histopathological examination. RESULTS: Up to 120 days after irradiation no differences were observed between the glands or between the different irradiation schedules. Beyond 120 days, however, the parotid gland performed better in flow rate and lag phase after fractionated irradiation, when compared to the submandibular gland. The observed differences in function corresponded with the observed late histopathological changes. The parotid gland contained more acinar cells and had a higher gland weight. No differences were observed between both fractionation schedules on each gland. CONCLUSIONS: The main observation from this study is the higher radiosensitivity of the submandibular gland compared to the parotid gland for late effects after fractionated irradiation. This may have implications for the treatment planning in case of radiotherapy for head and neck cancer.

Animals↗
PubMed1984

Inhibitory effect of androgen on the synthesis of proteinase F in the male mouse submandibular gland.

Androgenic regulation of one of the esteroproteinases (proteinase F) in the mouse submandibular gland was studied using specific antiserum. In contrast to esteroproteinases such as proteinases A, D or P-esterase, proteinase F content in male but not in female mice was increased by gonadectomy and decreased by the injection of various androgens. In-vivo incorporation of [3H]leucine into proteinase F in males was increased after castration and decreased by the injection of testosterone propionate; androgens inhibited the de-novo synthesis of proteinase F in male mice. The dose-response curves for testosterone propionate and time-courses following castration or after the injection of testosterone propionate were reciprocal between proteinase F and total esteroproteinase activity. Proteinase F, like other esteroproteinases in the submandibular gland of the mouse, was localized in granular convoluted tubular cells. These data indicate that granular convoluted tubular cells of the male mouse submandibular gland synthesize both androgen-inducible proteinases and androgen-inhibitory proteinase (proteinase F).

Androgens↗
PubMed2002

Effects of electrohydraulic extracorporeal shock wave lithotripsy on submandibular gland in the rat: electron microscopic evaluation.

OBJECTIVES: Extracorporeal shockwave lithotripsy (ESWL) has been applied in sialolithiasis as a new treatment modality. The aim of this experimental study is to investigate the local effects of electrohydraulic ESWL applied to the right submandibular gland of the rats. METHODS: This prospective study was conveyed in four groups; groups I, II, III and IV; each group consisting of 20, 20, 18 and 9 rats, respectively, with a randomized distribution. Groups I, II, III and IV received 250, 500, 1000 and 2000 shock waves at 14-16 kV (average 15.1 kV), respectively, to the right submandibular glands on the 0th day. In groups I, II, III, right submandibular glands of the rats were removed on the 0th, 1st, 7th and 15th days; in group IV, this procedure could be managed only on the 0th and 7th days. Light and electron microscopic evaluation were assessed. Using the light microscopic changes, severity of damage score of the glands (SDS) was found. Statistical analysis was done using SDSs. RESULTS: Light and electron microscopic observations have shown that the damage produced by the shock waves were confined to focal areas in the acinar cells (AC), granulated convoluted tubule (GCT) cells and blood vessels at all doses applied. Vacuolization in the cytoplasms of the AC and GCT cells, disintegration of membranes, alteration in the cytoplasmic organization, swelling of the mitochondria and loss of the features were observed on electron microscopy. Increase in the secretion rate; stasis and dilatation in the blood vessels; blebbing and loss of features in the cytoplasm of the endothelial cells were observed. According to the result of the statistical analysis using SDSs; at 250 shock wave dose, a statistically significant difference between the SDSs of the days (0th, 1st, 7th and 15th) was found (P<0.05). The SDS on the 0th day was found to have the lowest value among the other days. And also a statistically significant difference was found on the 0th day between the SDSs at doses of 250, 500, 1000 and 2000 shock waves (P<0.05). The SDS at 250 and 500 shock waves was found to have the lower value than the SDS at the 2000 shock wave. It was observed that produced damage was less prominent by small doses (250, 500 doses) initially (0th day). Electrohydraulic ESWL caused a "patchy type" generalized pathology on submandibular glands of the rats and damaged focal areas were widespread all through the gland from the 1st day on. CONCLUSION: Formation of the damage was concluded to be related to the direct effect of the shock waves rather than the dose used. Electrohydraulic lithotripters are not suitable for sialolithiasis because of the focus problems, local tissue damage and the risk of the damage to the adjacent structures.

Animals↗
PubMed1991

Mouse submandibular gland prorenin-converting enzyme is a member of glandular kallikrein family.

Mouse submandibular gland prorenin-converting enzyme (PRECE) consists of the two polypeptide chains of 17 and 10 kDa and cleaves mouse Ren-2 prorenin at a dibasic site to yield mature renin. Western blot analysis using an antiserum against this enzyme gave rise to multiple bands in mouse submandibular glands, suggesting that PRECE is a member of a protease family. Partial amino acid sequence analysis of purified PRECE and cloning and sequence analyses of its cDNA indicated that it is identical to the mGK-13 gene product, epidermal growth factor-binding protein type B, which is a member of the glandular kallikrein family and is involved in maturation of epidermal growth factor. Conditioned medium from Chinese hamster ovary cells transfected with an expression plasmid for PRECE had prorenin converting activity. These results indicate that PRECE is involved in the maturation of two bioactive polypeptides expressed in mouse submandibular glands, Ren-2 renin and epidermal growth factor.

Amino Acid Sequence↗
PubMed1996

Initial transient phase of salivary secretion by the submandibular glands of rats under anoxic conditions.

Salivary secretion of the rat submandibular gland exhibits two phases upon administration of acetylcholine (ACh, 10(-6) M): an immediate initial transient phase of rapid secretion lasting 5 min followed by a longer steady phase of slower secretion. Application of an anoxic perfusate bubbled with 100% N2 for 10-20 min had no effect on the initial phase of secretion, but caused a marked decrease in secretion in the steady phase following stimulation with 10(-6) M ACh. After secretion under the anoxic condition, a recovery period without stimulation was performed for 30 min by perfusion with HEPES Ringer's solution bubbled with 100% O2 and containing various potassium concentrations. The initial secretion rate measured with application of an anoxic perfusate was markedly increased by the high-K+ recovery perfusate (25 mM) and decreased by the K(+)-free recovery perfusate. Administration of 10(-3) M ouabain in the normal perfusate resulted in inhibition of secretion during the steady phase similar to that seen under the anoxic condition, while the secretory rate during the initial phase remained unchanged. We concluded that the initial phase of secretion is relatively resistant to anoxia, and that oxygen supply and Na(+)-K+ pump activity were essential for maintaining the steady phase of secretion.

Acetylcholine↗
PubMed2003

Oncocytic carcinoma arising in submandibular gland with immunohistochemical observations and review of the literature.

We report a case of oncocytic carcinoma arising in submandibular gland. The tumour occurred in the left submandibular gland of an 82-year-old Japanese man. Histologically, the tumour was mostly composed of large cells with eosinophilic granules in the cytoplasm and they were arranged in the solid sheets, islands with duct-like structure and cords. The tumour cells had aggressively invaded muscles and perineural tissues, and cervical lymphatic metastasis was frequently observed. Histochemically, the tumour cells were strongly positive for phosphotungstic acid-hematoxylin (PTAH) stain, and we diagnosed this malignant tumour as oncocytic carcinoma. Immunohistochemically, the tumour cells reacted positively for cytokeratin 7, 8, 19, epithelial membrane antigen (EMA), alpha-1-antichymotrypsin and carcinoembryonic antigen (CEA), but negative for cytokeratin 13, 14, smooth muscle actin (HHF35) and S-100 protein (S-100). Tumour was diagnosed as oncocytic carcinoma in submandibular gland. Its characteristics are discussed in term of its histopathological and immunohistochemical features.

Adenocarcinoma↗
PubMed1993

An experimental study of chondrogenesis and osteogenesis in rat submandibular gland induced by implantation of demineralized dentin.

Demineralized dentin pieces were implanted in 18 rat submandibular glands to examine the chondrogenesis and osteogenesis in pleomorphic adenoma of the salivary gland. After 7 days of implantation, a large amount of cartilage tissue was found next to the inner portions of the implanted pieces, and small amounts of the osteoid and cartilage tissues were detected next to the outer portions. A small amount of bone tissue was found in contact with the cartilage 10 days after the implantation. In the inner portions, invasions of capillaries and a small amount of osteoid tissue were noted. These histological findings resembled those of endochondral ossification. Large amounts of bone tissue and resorption of the implant were observed after 14 days. It has been suggested that cartilage and bone are produced by bone morphogenetic proteins (BMP) in demineralized dentin resulting in chondrogenesis followed by osteogenesis in submandibular gland. Apparently, undifferentiated mesenchymal cells are produced by implantation, undergo dedifferentiation, and are redifferentiated into chondroblasts and osteoblasts in the presence of BMP. These results suggest that chondrogenesis and osteogenesis in the submandibular gland are induced by BMP. It is possible that the chondroid tissues in pleomorphic adenoma of the salivary glands are induced by proteins such as BMP.

Adenoma, Pleomorphic↗
PubMed1997

Megamitochondria in the serous acinar cells of the submandibular gland of the neotropical fruit bat, Artibeus obscurus.

BACKGROUND: As part of a continuing investigation of the comparative ultrastructure of chiropteran salivary glands, we examined the submandibular glands of eight species of neotropical fruit bats in the genus Artibeus. We previously described secretory granules of unusual substructure in the seromucous demilunar cells of this organ in some species in this genus. In the present study, we turned our attention to the serous acinar cells in the same glands. METHODS: Specimens of eight species of Artibeus were collected in neotropical localities. Salivary glands were extirpated in the field and thin slices were fixed by immersion in triple aldehyde-DMSO or in modified half-strength Karnovsky's fixative. Tissues were further processed for electron microscopy by conventional means. RESULTS: In contrast to seromucous cells, which exhibit species-specific diversification in bats of this genus, the secretory apparatus and secretory granules in the serous acinar cells are highly conserved across all seven species. The single exception involves the mitochondria in one species. In this instance, some of the serous cell mitochondria in Artibeus obscurus are modified into megamitochondria. Such organelles usually have short, peripheral cristae; a laminar inclusion is present in the matrix compartment of every outsized organelle. Inclusions of this nature never are present in normal-size mitochondria in the serous cells. None of the megamitochondria were observed in the process of degeneration. CONCLUSIONS: The giant mitochondria in A. obscurus have a matrical structure that is radically different from that of the only other megamitochondria reported to occur in bat salivary glands. The factors that lead to variation in megamitochondrial substructure in different species, as well as the functional capacities of such giant organelles, are unknown.

Animals↗
PubMed1993

Distribution of calcitonin gene-related peptide immunoreactive nerve fibers in the human submandibular gland.

The indirect immunofluorescence technique was used to study the distribution of calcitonin gene-related peptide (CGRP) in human submandibular gland. A relatively low number of thin varicose fibers with intense immunofluorescence for CGRP was seen in samples from seven glands. These CGRP-immunoreactive (CGRP-IR) nerve fibers were mainly seen around or in close contact with intra- and interlobular blood vessels. Some CGRP-IR nerve fibers were also found in association with intra- and interlobular salivary ducts and a few around the submandibular acini. By visual estimation there was no difference in the density of CGRP-IR nerve fibers between specimens of recurrent duct obstruction and laryngeal carcinoma. The present results show that the distribution of CGRP-IR nerve fibers in the stroma and in the glandular secretory elements of the human submandibular gland is quite similar to that seen in the rat and the ferret, which have been reported earlier. Furthermore, the regional distribution of CGRP-IR fibers in the human submandibular gland suggests that CGRP has a physiological role in the regulation of salivary gland function in human salivary glands, e.g. blood flow and secretion.

Adult↗