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Histochemical demonstration of monoaminergic and cholinesterase-positive nerve fibres in regenerating rat submandibular gland autografts.

A cholinesterase localization method and a monoamine histofluorescence technique were used to locate nerve fibres in regenerating rat submandibular gland autografts. Experimental rats had a portion of one submandibular gland excised and cut into small fragments which were autografted immediately into the middle one-third of the tongue. Control rats had a portion of one submandibular gland removed and discarded, and their tongues were sham-operated. Seven to ten weeks later, the rats were killed and the tongues were removed, frozen and sectioned in a cryostat. A light microscopical study of the tongue sections subjected to the cholinesterase technique showed that the submandibular gland autografts contained many nerve fibres that exhibited cholinesterase activity. These cholinesterase-positive nerve fibres were distributed throughout the autografts. The fibres were associated with the numerous duct-like structures and the less numerous acini. In addition, ultraviolet illumination of tongue sections after treatment with a glyoxylic acid mixture revealed histofluorescent monoaminergic nerves within the autografts. These fibres were less prominent than the cholinesterase-positive fibres and appeared to run primarily along blood vessels within the autografts. The results suggest that autonomic nerves are present within regenerating submandibular gland autografts.

Animals↗

Spindle cell mucoepidermoid carcinoma of submandibular gland.

A malignant tumor of the submandibular gland was found to consist predominately of spindle cell elements that initially suggested a primary sarcoma. Further examination revealed that the spindled malignant cells were derived from a high-grade mucoepidermoid carcinoma.

Aged↗

[Histochemical studies of the parotid and submandibular glands of humans].

Human parotid and submandibular glands were studied using histological techniques. Proteins rich in arginine, tyrosine, cystine-cysteine and tryptophan were present within secretory granules of seromucous acini and ducts of both glands. Acid phosphatase, ali-esterase, peroxidase and 3-beta-steroid-dehydrogenase were also demonstrated in the two glands.

Adult↗

Anatomic study of submandibular gland transfer in an attempt to prevent postradiation xerostomia.

Xerostomia is the most common negative sequela after radiotherapy for head and neck cancer and results from destruction of normal salivary gland tissue by radiation. We hypothesized that transferring a single submandibular gland outside the radiation field to the submental region may preserve its function, thus preventing xerostomia and its consequences. This anatomic study was designed to evaluate different methods of submandibular gland transfer to the submental region. Eight submandibular glands were dissected in four fresh human cadavers. The anatomy and blood supply of the region were documented. Each gland was transferred to the submental region by either free microvascular transfer or based on retrograde flow through the distal facial vessels. Both methods of transfer resulted in complete relocation of the submandibular gland into the submental region.

Cadaver↗

Hormonal regulation of epidermal growth factor and protease in the submandibular gland of the adult mouse.

The structure of the granular convoluted tubules of the mouse submandibular gland is influenced by androgens, adrenal steroids, and thyroid hormones. We wished to investigate the effects of variations in hormonal status on the quantitative and qualitative distribution of two secretory products of these tubules, epidermal growth factor (EGF) and protease. The effects of the thyroid and adrenal glands on EGF content and protease activity of the submandibular glands of adult female mice were studied by RIAs (EGF), enzyme assays (protease), and immunocytochemical methods. In animals rendered chronically hypothyroid by propylthiouracil (4 months) or in animals which were adrenalectomized and ovariectomized (3 weeks), protease activity and EGF levels were reduced by 81-97%. The administration of testosterone induced these polypeptides even in hypothyroid animals. Daily administration of L-T4 (T4; 1 micrograms/g BW) for 7 days increased EGF and protease activity 3.6-fold in intact mice and reversed the effect of hypothyroidism. EGF and protease were also induced by T4 in adrenalectomized and ovariectomized mice, although to a lesser degree than in intact animals. Immunocytochemical stainings of submandibular glands indicated that the number of granular convoluted tubule cells immunoreactive for EGF correlated with the levels of EGF determined by RIAs. With respect to immunostaining for protease, such a correlation was not observed. The data indicate multihormonal regulation of EGF and protease in the mouse submandibular gland.

Adrenal Glands↗

[Prophylactic neck dissection for submandibular gland cancer].

The indication and preferred dissection field for prophylactic neck dissection for submandibular gland cancer are controversial and have not been standardized. We reviewed 27 patients who underwent a definitive operation for previously untreated submandibular gland cancer. The 27 patients consisted of 13 patients with adenoid cystic carcinoma, 6 patients with mucoepidermoid carcinoma, 6 patients with adenocarcinoma, and 2 patients with squamous cell carcinoma. The diagnostic accuracies of malignancy and histology with fine needle aspiration cytology were 86% and 56%, respectively. In sixteen out of 21 cases without neck lymph node metastasis, a prophylactic neck dissection was performed and pathological neck lymph node metastases were detected in five cases. On the other hand, in five cases that did not receive a prophylactic neck dissection, latent neck lymph node metastasis was observed in 2 cases. In both cases of neck lymph node metastasis, pathological positive lymph nodes were observed in only level 2 or level 3. The rates of occult neck lymph node metastasis according to the T stage were 0% in T1, 33.3% in T2, 57.1% in T3 and 100% in T4. The rates of occult neck lymph node metastasis according to the histopathology were 46.2% in adenoid cystic carcinoma, 50% in mucoepidermoid carcinoma, 50% in adenocarcinoma, and 50% in squamous cell carcinoma. In conclusion, we believe that supraomyohoid neck dissection is suitable for N0 cases of submandibular gland cancer because of four reasons: 1) rate of occult neck lymph node metastasis in submandibular gland cancer is high, 2) pathological neck lymph node metastasis in N0 cases and latent neck lymph node metastasis were observed in level 2 and level 3, 3) the prognosis of cases with neck lymph node metastasis was poor, and 4) same skin incision can be used not only for the primary resection but also for the neck dissection.

Adult↗

Metachronous bilateral submandibular gland metastases from carcinoma of the breast.

Metastases to the salivary glands from distant neoplasms are unusual, with most reported cases involving the parotid gland. Metastatic deposits in the submandibular gland are extremely rare with bilateral involvement not previously reported. We present the case of a patient with advanced breast carcinoma who has had metachronous involvement of both submandibular glands and review the literature on this subject.

Adenocarcinoma↗

Endoscopic excision of the submandibular gland by an intraoral approach.

The recent advent of endoscopic procedures has compelled both plastic and neck and head surgeons to reconsider the conventional methods by which the excision of submandibular gland is classically achieved. An endoscopic intraoral approach for excision of the submandibular gland is described. This procedure is anatomically safe and can be made with minimal morbidity; a transcervical incision is avoided. Both specific instruments and solid anatomical knowledge are necessary to perform a safe and efficient glandular endoscopic excision. The essential surgical steps are as follows: 1) Careful identification of the Wharton duct and lingual nerve; 2) Retraction of the mylohyoid muscle; 3) Protection of the sublingual gland and lingual nerve; 4) Extraoral manipulation of the submandibular gland obtaining intraoral protrusion; and 5) Careful dissection of the posterior third of gland, avoiding injury on the facial artery and vein. Two patients were operated on with this technique and were very pleased with their results. No complications were registered. With advanced endoscopic instruments, new surgical technique, and surgeon experience, endoscopic intraoral excision of the submandibular gland can be the method of choice in benign neoplasia, sialolith, sialoadenitis and plunging ranula.

Adult↗

Fine-needle aspiration cytology of submandibular gland lesions.

The usefulness of fine-needle aspiration cytology (FNAC) in the diagnosis and treatment of submandibular gland lesions is not well known. The 210 FNACs taken from submandibular gland lesions at Turku University Central Hospital between 1984 and 1991 were reviewed. Of these FNACs, 78 samples from primary lesions were confirmed histologically. Within this subset 10 FNACs were taken from benign neoplasms, all of which were correctly classified (sensitivity 100 per cent; specificity 88 per cent). Only four of the 14 FNACs from malignant lesions were cytologically considered malignant (sensitivity 29 per cent). On the other hand, four FNACs raised a false suspicion of malignancy (specificity 6 per cent). Out of 54 FNACs from non-neoplastic lesions 43 were correct (sensitivity 80 per cent; specificity 63 per cent). There were 104 patients (123 FNACs), who had not been operated on: the follow-up of these patients shows that in this subset of FNACs there were no false malignant but probably one false benign finding (1 per cent). We conclude that FNAC can offer valuable information about the type of the submandibular gland lesion, but the decision of operative and other treatment should not be based solely on the result of FNAC.

Adenoma, Pleomorphic↗

Response of submandibular gland of the rat to nutritional zinc deficiency.

Studies in several laboratories have shown that nutritional Zn deficiency in the rat causes a reduction in the activity of certain Zn-dependent enzymes in kidney, intestine, pancreas, etc. The present report deals with the effects of Zn-deficiency on submandibular gland of the rat. For the sake of comparison with previous studies, some assays on pancreas were included. Protein content, DNA, acid phosphatase, and acid protease activities were not affected in submandibular gland. Lactate dehydrogenase was unaffected in submandibular gland and showed increased activity in pancreas. Malate dehydrogenase was significantly decreased in both organs, the decrease being more marked in submandibular gland. Alkaline phosphatase activity in submandibular glands of control rats was about 10-fold higher than in pancreas. In the zinc-deficient rats, alkaline phosphatase was reduced to 59% of controls in the submandibular glands and to about 75% in pancreas. It is known from histochemical studies that in the submandibular gland this enzyme is confined to the myoepithelial cells. Recent studies attribute to salivary glands a role in the etiology of taste disturbances seen in clinical states of zinc deficiency. It is proposed that functional impairment of the myoepithelial cells might contribute to the disturbance of taste.

Acid Phosphatase↗

Radiation-induced decreases of serous cell immunoglobulin excretions in the rat submandibular gland.

The effect of radiation on the submandibular glands of the rat was studied with special reference to the immune reactivity of IgG and IgA. These immunoglobulins are localized in the serous cells and were influenced by irradiation. Radiation therapy markedly reduced the reactivity for both IgG and IgA. Immunocytochemistry showed a good correlation to the deteriorated morphology as revealed by light and electron microscopy. The local excretion of immunoglobulins in the submandibular gland can thus be affected by radiation and results in an increased risk for oral infections. Pretreatment of animals with the secretagogue cyclocytidine caused less pronounced damage in cellular ultrastructure and immunological findings, as observed by fluorescence microscopy.

Ancitabine↗

Nerve growth factor-induced increase in [3H]thymidine incorporation into parotid and submandibular glands of young rats and its partial blockade by propranolol or partial sialoadenectomy.

Administration of nerve growth factor (NGF) twice daily for 2 days to young rats (11 days old at the time of the initial injection) resulted in an 8.1-fold increase in [3H]thymidine levels of the parotid gland, and a 9.7-fold increase in levels of the submandibular gland when compared to untreated controls. Isoproterenol (ISO), a beta-adrenergic receptor agonist, caused an 8.7-fold increase in [3H]thymidine incorporation into DNA of the parotid gland, and a 10.7-fold increase in [3H]thymidine in the submandibular gland when compared to controls. The increase in thymidine was accompanied by parotid gland enlargement as well as an increase in cell surface beta 1-4 galactosyltransferase, an enzyme whose expression has been associated previously with acinar cell proliferation. Administration of NGF and ISO together were not additive in their effects on the parotid and submandibular glands. The introduction of propranolol, a beta-adrenergic receptor antagonist, completely negated the ISO effects on the salivary glands but was only partially effective in blocking the NGF effects on the glands. An assay of parotid levels of norepinephrine showed NGF treatment to cause an increase in gland-associated levels of neurotransmitter. Removal of the submandibular/sublingual glands prior to administration of ISO prevented the above changes in the parotid gland. NGF administered to partially sialoadenectomized rats was also less effective in inducing parotid gland hypertrophy and hyperplasia. Simultaneous administration of NGF and ISO to the partially sialoadenectomized rats had an additive influence on [3H]thymidine incorporation, galactosyltransferase expression and gland hypertrophy. The results suggest that NGF influences salivary gland cell growth in part through activation of cell-surface beta-adrenergic receptors.

Animals↗

Are the prejunctional alpha 2-adrenoceptors of the rat vas deferens and submandibular gland of the alpha 2A- or alpha 2D-subtype?

We have investigated the effects of antagonists at functional prejunctional alpha 2-adrenoceptors of rat was deferens and rat submandibular gland and compared potencies with affinities for the alpha 2A-, alpha 2B- and putative alpha 2D-ligand binding sites of human platelet, rat kidney, and rat submandibular gland, respectively. Prejunctional potency of antagonists was expressed as an EC30 (concentration producing a 30% increase in stimulation-evoked release of tritium in tissues pre-incubated with [3H]noradrenaline) in rat vas deferens and submandibular gland, and also as a pA2 (antagonist concentration producing a 2-fold shift in the inhibition by the alpha 2-adrenoceptor agonist xylazine of the electrically-evoked isometric twitch) in rat vas deferens. The functional prejunctional alpha 2-adrenoceptors of rat vas deferens and submandibular gland are alpha 2A-like since there was a good correlation between affinity for the alpha 2A-ligand binding site in human platelet and prejunctional potency in rat vas deferens (r = 0.90, n = 7, P less than 0.001), and submandibular gland (r = 0.84, n = 7, P less than 0.05). However, there was a better correlation between affinity for the alpha 2-ligand binding site of rat submandibular gland and prejunctional potency in rat vas deferens (r = 0.95, n = 7, P less than 0.001), and submandibular gland (r = 0.97, n = 7, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

Characterization of the major and minor mucus glycoproteins from bovine submandibular gland.

Two mucins were isolated from bovine submandibular glands and termed major and minor on a quantitative basis. The major mucin representing over 80% of the total glycoprotein fraction contained 37% of its dry weight as protein in contrast to 62% for the minor mucin. Differences in the amino acid composition reflected the higher proportion of typically non-glycosylated peptide in the minor mucin. The molar ratio of N-acetylgalactosamine to serine plus threonine was 0.82 in major and 0.65 in minor mucins, indicating a lower degree of substitution of potential glycosylation sites in the minor mucin. Differences in the carbohydrate composition were found largely related to the sialic acids, with higher relative amounts of N-glycoloylneuraminic acid in the minor mucin. In addition, the proportion of di-O-acetylated sialic acids was higher in the major mucin. The rate of sialidase action on the two mucins could be correlated with the content of N-glycoloylneuraminic acid in each glycoprotein. There was no difference in the type of oligosaccharide found in each mucin and the differences in relative proportions reflected the monosaccharide composition for the two mucins. Gel filtration on Sepharose CL 2B showed a lower molecular weight distribution for the minor in contrast to the major mucin which was partially excluded. Density gradient centrifugation reflected this variation. SDS-PAGE demonstrated a regular banding pattern for the major mucin with a lowest subunit size of 1.8 x 10(5) Da and aggregates in excess of 10(6) Da, while the minor mucin ranged from 3.0 x 10(5) to 10(6) Da. The chemical composition of the isolated mucins was compared with previous histochemical analysis of mucin distribution in bovine submandibular glands and indicates a possible cellular location for each mucin.

Acetylation↗

Regulation of salivary kallikrein secretion in submandibular gland.

Unstimulated pairs of rat submandibular glands were compared with regard to their wet weight, total protein content and kallikrein antigenic activity. Paired glands from the same animal were found to be comparable, whereas differences from one animal to another were considerable. One of two paired glands was extirpated and used as control, and the other was subsequently subjected to stimulation. Salivary secretion was induced parasympathomimetically (intraperitoneal injections of pilocarpine; perfusion with acetylcholine and electrical stimulation of the ductal nerve plexus near the gland hilus) or sympathomimetically (cervical sympathetic nerve stimulation with or without administration of alpha- or beta-adrenergic blocker; perfusion with epinephrine, norepinephrine or isoproterenol). The effect was studied by measuring the change in total gland kallikrein content and by quantitation of kallikrein in saliva. A small secretion of kallikrein was always observed. However, alpha-adrenergic stimulation was 40 and 1 500 fold more effective in releasing kallikrein than beta-adrenergic and parasympathomimetic stimulation, respectively. Also, significantly more kallikrein was released by beta-adrenergic than parasympathomimetic stimulation. Immunohistochemistry confirmed the observed depletion of kallikrein following alpha-adrenergic stimulation. No alteration in kallikrein localization was observed in stimulated glands.

Acetylcholine↗

Quantitative analysis of the submandibular gland using computed tomography.

OBJECTIVE: To evaluate the normal variation in size of the submandibular gland from computed tomographic (CT) scans. MATERIALS AND METHODS: CT was performed parallel to the Frankfurt horizontal (FH) and mandibular (MP) planes in 130 subjects (64 men and 66 women) with healthy submandibular glands, six patients with sialoadenitis and four with masseteric hypertrophy. RESULTS: The mean (s.d.) maximum cross-sectional area (MCSA) of the submandibular glands for FH was 324 (89) mm2 and for MP 364(101) mm2. There was a high correlation between individuals' right and left glands. There was no significant difference in the mean MCSA between the right and left, which varied by less than 10%. The mean (s.d.) volume of the gland was 8072 (2574) mm3. With a high correlation with mean MCSA in both scanning planes, the mean MCSA may be an indicator of the volume of the gland. MCSA increased significantly with body height, weight and body mass index, but decreased with age. The MCSA of the affected side in patients with sialoadenitis and masseteric hypertrophy was larger than both that of the normal side and the predicted values. CONCLUSION: MCSA is a useful indicator of gland volume, and differences of greater than 10% between the two sides may be used in the diagnosis of submandibular gland disease.

Adult↗

Immunocytochemical localization and concentrations of the alpha and gamma subunits of 7S-nerve growth factor in the submandibular gland of the mouse.

For unexplained reasons, nerve growth factor (NGF) exists in very high concentrations in the submandibular gland of the mouse. The NGF in the gland, called 7S-NGF, is a non-covalent complex of three protein subunits, named alpha-, gamma- and beta-NGF. All the known biological activity resides in the beta-NGF subunit, and previous studies have shown that beta-NGF is present in much greater concentrations in the male submandibular gland than in the female gland. The higher concentration in the male is due to the fact that beta-NGF is synthesized in the granular tubule cells of the submandibular gland. These cells are much more numerous in the male gland. In contrast to beta-NGF, neither the concentrations of alpha and gamma subunits nor their cellular localization in the mouse submandibular gland have been established. In this study, radioimmunoassays specific for alpha and gamma subunits determined that both are present in much higher concentrations in the male gland. Immunocytochemical work localized both subunits in the granular tubule cell in the male and female submandibular gland. This indicates that all the components of 7S-NGF exist in a single cell type in the gland and suggests that 7S-NGF can be formed within this cell and secreted as a complex into the saliva.

Animals↗