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Comparison of 7S nerve growth factor and nerve growth factor I from mouse submandibular glands.

7S nerve growth factor (7S NGF) and nerve growth factor I (NGFI) are NGF-containing protein complexes isolated from mouse submandibular glands by different protocols, and reports suggest that the molecules differ chemically. In this study, we compared the molecular properties and subunit compositions of the two proteins. Purified 7S NGF and NGFI electrophoresed to identical positions on polyacrylamide gels in nondissociating buffers, with electrophoretic mobilities indistinguishable from that of unpurified NGF in salivary gland extracts. Ultraviolet absorption curves were identical, and sedimentation coefficients were similar (7.3 +/- 0.25 S for 7S NGF; 7.2 +/- 0.2 S for NGFI) as determined by sedimentation velocity analysis. By sedimentation equilibrium analysis, molecular weights of 135 000-140 000 were obtained for both complexes at protein concentrations in the centrifuge cell greater than 85 micrograms/mL; when protein concentrations within the centrifuge cell ranged from approximately 30 to 100 micrograms/mL at equilibrium, both complexes dissociated. Molecular weight values determined by gel filtration on Bio-Gel P300 and Sephadex G200 resins were similar for both proteins, and the values determined on Sephadex agreed with those obtained by ultracentrifugation. The subunit compositions of the complexes were also similar as determined by nonequilibrium isoelectric focusing, NGFI being composed of proteins that migrated to positions identical with those of the alpha, beta, and gamma subunits of 7S NGF. Furthermore, the stoichiometry of the subunits was similar in the two complexes as determined by radioimmunoassays to each of the subunits and by densitometric analysis of electrophoretic gels. Both methods showed that the complexes contain approximately 2 mol of the alpha and gamma subunits per mole of beta-NGF.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Activation of ouabain-sensitive p-nitrophenylphosphatase by carbachol and cGMP in rat submandibular gland.

Na+,K+-ATPase activity was monitored by measuring ouabain-sensitive K+-dependent p-nitrophenylphosphatase (p-NPPase) activity in rat submandibular gland slices. Carbachol (carbamylcholine chloride) stimulated the p-NPPase activity in the presence of calcium but not in its absence. Carbachol activation of the enzyme was totally ouabain sensitive and could be blocked by atropine. A minimal requirement of sodium ion extracellularly was required for this carbachol stimulation. cGMP and its dibutyryl analogue was also effective in stimulating the enzyme activity, whereas, cAMP was ineffective. Calcium, however, was not required for cGMP activation of the p-NPPase activity. The result indicates that calcium is the second messenger and cGMP is the tertiary connection between cholinergic stimulation and Na+,K+-ATPase activation in these glands. Activation of Na+,K+-ATPase is postulated to be responsible for primary fluid formation.

4-Nitrophenylphosphatase↗

[Changes of three types in the secretory systems present in the rat submandibular glands during aging].

Changes of the three types, termed here as alpha, beta and gamma, in the secretory functions present in the submandibular glands (SMG) of male rats were observed throughout almost all animal lives from 2 weeks to 24 months of age, by measuring changes of the wet weights of the SMG, salivary volumes secreted, the concentrations of protein, calcium and inorganic phosphate, and the types of proteins secreted in response to alpha-methylnoradrenaline (alpha-mNA) for the alpha-type, isoproterenol (IPR) for the beta-type and clonidine (Clonid) for the gamma-type, volumetrically, colorimetrically, atomic absorption-pectrophotometrically and isoelectric focusing electrophoretically. The molecular weight, isoelectric point and some posttranslational variations of a purified protein were elucidated by SDS-polyacrylamide gel electrophoresis (PhastSystem), isoelectric focusing electrophoresis (IEF, PhastSystem) on gradient pH 3.5 to 5 gels and neuraminidase or alkaline phosphatase treatment. The localization in the SMG, the inhibitory effects on the BrdU incorporation of the cultured thymocytes and the adhesive properties to the acrylic resin plate of this antigen were also analyzed by the indirect immunofluorescence, IEF and protein detection methods. The wet weights of the SMG were substantially increased up to 3.5 months of age with a positive correlation to body weight, but thereafter it reached the plateau level up to 24 months of age, somewhat different from changes of body weight. The salivary volumes as well as the amounts of protein secreted in response to alpha-mNA, IPR and Clonid were positively correlated to the wet weights of the SMG throughout the animal life. The concentration of calcium in the three types of secretions was positively correlated to the protein concentration, whereas the concentration of inorganic phosphate was tended to be reversely correlated to the salivary flow rate with some exceptions throughout the animal life. The gamma-type of proteins was not greatly changed, whereas the alpha- and beta-types of proteins were greatly changed in some proteins quantitatively or qualitatively throughout the animal life.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Small cell undifferentiated carcinoma of the submandibular gland with neuroendocrine features.

This article reports the clinical, histopathologic, and immunohistochemical findings in a case of small cell undifferentiated carcinoma of the submandibular gland. The tumor was composed of anaplastic cells slightly larger than lymphocytes without ductal differentiation. On immunohistochemical analysis, the tumor contained cells that reacted positively with antibodies to cytokeratin, neuron-specific enolase, synaptophysin, and chromogranin. The present case supports the hypothesis that small cell undifferentiated carcinomas of the salivary glands arise from presumed multipotential ductal stem cells. When this tumor entity is located on the salivary glands, it appears to behave less aggressively than when it is a primary tumor of the bronchial tree.

Carcinoma, Small Cell↗

Localization of an ecto-ATPase/cell-CAM 105 (C-CAM) in the rat parotid and submandibular glands.

We investigated an ecto-ATPase/cell-CAM 105 (C-CAM), previously shown to be distinct from the Ca2+ pump, in rat parotid and submandibular glands. Polyclonal antibodies raised against the enzyme were employed using indirect immunofluorescence, peroxidase-anti-peroxidase (PAP), and electron microscopic immunogold labeling procedures to visualize the location of the enzyme. In the PAP-stained sections and with immunofluorescence, labeling was observed on the luminal and lateral surfaces and the intercellular canaliculi of the acinar cells of both glands. The luminal surface of the intercalated ducts was brightly stained, whereas those of the striated and excretory ducts were less prominently labeled. The basal surface of the acinar cells in the parotid gland and the lateral and basal surfaces of the duct cells were not labeled. Apparent labeling was observed on the basal surface of the submandibular acinar cells. Electron microscopy revealed that for both glands the enzyme was primarily localized along the luminal border of the acinar cells, mainly in association with microvilli, with slightly less reactivity along the intercellular canaliculi and lateral borders and relatively little along the basolateral membranes. Gold labeling was also observed on the luminal borders of the intercalated and striated ducts. Possible functions of the C-CAM include breakdown of ATP, stabilization of the microvillar membranes, cell adhesion, and involvement in secretory mechanisms.

Adenosine Triphosphatases↗

Leukocytes infiltrating the submandibular glands of NOD mice express E-cadherin.

Sjögren's syndrome [SS] is typified by infiltration of mononuclear cells [MNC] into the salivary and lacrimal glands, although the biological role of these infiltrating cells remains unclear. We report here that E-cadherin, which mediates cell-cell adhesion and regulates differentiation, proliferation, and apoptosis of epithelial cells, is expressed ectopically by MNC in the salivary glands in the NOD mouse model of SS. Flow cytometric analysis of CD45(+)cells from NOD submandibular glands revealed that over 90% express E-cadherin. More detailed phenotypic analyses demonstrated that E-cadherin expression is high (>90%) among mature T cells (CD3(+)), B cells (CD19(+)), NK cells (DX5(+)), and monocyte/macrophages (CD11b(+)) within the infiltrates. Expression of other surface antigens, such as CD90 and CD117, above expected values suggests the presence of immature leukocytes, possibly of the T cell lineage, within the foci. We also present evidence that E-cadherin-expressing T cells in the glands do not exhibit normal proliferative responses to immobilized anti-CD3 antibody. While infiltrating MNC are not likely to be the direct cause of salivary hypofunction, the expression of E-cadherin by these cells may have implications for the progression of disease.

Animals↗

Direct evidence for the location of kallikrein in the striated ducts of the cat's submandibular gland by the use of specific antibody.

Kallikrein was located in the apical portion of the striated duct cells of the cat's submandibular gland by an immunohistochemical technique. This portion only of these cells showed an intense band of specific fluorescence. There was no evidence of specific fluorescence in the acinar and demilune cells nor in the interstitial tissue or blood besells. In some sections the collecting ducts showed a very fine fluorescent luminal rim.

Animals↗

Epidermal growth factor-like material in rat submandibular gland.

By using an antiserum specific for mouse epidermal growth factor (EGF), only the granular convoluted tubule (GCT) cells revealed immunochemical staining in rat submandibular glands. There was no regular sexual difference in the frequency or size of immunoreactive cells. Extracts of gland contained an antigen which showed a complete cross-reactivity with mouse EGF in radioimmunoassays. The relative amounts of EGF, determined by a heterologous radioimmunoassay, were not significantly different in the glands of rats of the two sexes. Administration of testosterone caused an increase, in both sexes, in the number of GCT cells stained for EGF and in the amount of EGF in the gland. There was no significant sexual differeence in these two parameters after androgen treatment.

Animals↗

Oncocytic carcinoma of the submandibular gland: a case report and literature review.

Oncocytes are characterized by a remarkable number of mitochondria as demonstrated by electron microscopy. Oncocytomas are very rare tumors that are usually benign and typically occur in the parotid gland. Oncocytic carcinomas are exceedingly rare in the salivary glands. We describe a 69-year-old Japanese man with an oncocytic carcinoma of the submandibular gland. We reviewed 38 articles describing oncocytic carcinoma of the head and neck that included clinicopathologic features. Oncocytic carcinomas appear to arise from benign oncocytomas, or may also arise de novo. In oncocytic carcinoma of the head and neck, the presence of distant, rather than local lymph node, metastasis is the most important prognostic indicator.

Adenocarcinoma↗

Characterization of kallikrein isolated from rat submandibular glands by a simple and rapid purification procedure.

Numerous biochemical properties (e.g. Mr, carbohydrate content, pI) were determined for kallikrein isolated from rat submandibular glands by a simple, rapid purification procedure. The kinetic behaviour of the enzyme towards various inhibitors and synthetic substrates was investigated. The effects of different salts and detergents on the esterolytic activity of the rat tissue kallikrein were recorded.

Animals↗

Adenoid cystic carcinoma of the submandibular gland with symptomatic ovarian metastases.

We report the clinical and pathologic features of an adenoid cystic carcinoma of the submandibular gland that metastasized to the ovaries 10 years after initial presentation. A 30-year-old woman underwent excision of a right submandibular adenoid cystic carcinoma followed by regional external beam radiation therapy. Three years later, she underwent extended hepatic resection and localized radiotherapy to the hepatic region for metastatic disease. The patient was without evidence of disease for 7 years when she developed pelvic pain and a pelvic mass was found. A solid and cystic 10-cm left ovarian mass and a single metastatic tumor nodule involving the right ovary were excised via the laparoscope. Histologically, the tumor was identical to the patient's initial salivary gland neoplasm. The neoplastic cells were CAM 5.2 positive, S100 positive, muscle-specific actin positive, and smooth muscle actin positive. Ultrastructurally, characteristic pseudocysts (pseudolumina) with abundant basal lamina and true glandular lumina lined by short microvilli were present. Other than a single anecdotal account of a parotid gland adenoid cystic carcinoma, this case represents the first documented report of an adenoid cystic carcinoma of salivary gland origin that was associated with symptomatic ovarian metastases. This case demonstrates that the ovary is a potential site for metastatic disease many years following the diagnosis and treatment for a primary neoplasm however uncommon or remote the site of origin. Since metastatic adenoid cystic carcinoma can rarely present as an ovarian mass, a clinical history of this neoplasm should be heavily weighed in the differential diagnosis of any unusual ovarian tumor with a predominant cribriform, trabecular, or tubular pattern.

Adult↗

A probable submandibular gland defect in a prehistoric mandible.

The mandible of a prehistoric male Indian, 35 to 40 years old at death, displays a probable bilateral submandibular gland defect. This defect is described, its incidence in prehistoric and modern populations is reviewed, and a possible genetic etiology is proposed.

Adult↗

[Neurosarcoma of the submandibular gland arising in a pleomorphic adenoma. Apropos of a case].

A 71-year-old woman consulted for a tumor of the right submandibular gland that had been present for 4 years and had rapidly increased in size during the last two months. Histological examination of frozen sections and immunohistochemistry concluded to a poor differentiated sarcoma probably a neurosarcoma with residual pleomorphic adenoma component. In spite of wide resection, local recurrences with nodes and lung metastases occurred leading to the death of the patient. We think interesting to report this unusual salivary tumor and to discuss its pathological features.

Adenoma, Pleomorphic↗

Immunohistochemical localization of secretory immunoglobulins in the main excretory duct of the human submandibular gland.

The localization of IgA, IgG, and IgM was investigated immunohistochemically in the mucosal surface of the main excretory duct of the human submandibular gland in order to verify the possible antimicrobial properties of this duct. Only secretory IgA-immunoreactivity was recognized in the epithelial cells of the duct. An intense immunoreactivity was observed in the cytoplasm of some cells and at the luminal surface of most of the cells. Clusters of IgA-positive immuno-competent cells were also recognizable in the subepithelial layers. No reactivity for IgG and IgM was noticed. The results suggest that the ductal epithelium may actively be involved in the release of secretory IgA, which could play a prominent role in the local defense mechanism of the duct.

Adult↗

Flow cytometric DNA content of adenoid cystic carcinoma of submandibular gland. Correlation of histologic features and prognosis.

Flow cytometric analysis of nuclear DNA content was performed in 26 adenoid cystic carcinomas of the submandibular gland using archived, paraffin-embedded tissues. The DNA content was compared with multiple histologic parameters and clinical course. Ten carcinomas (38%) were aneuploid and 16 (62%) diploid. Aneuploid carcinomas demonstrated a higher frequency of solid cytoarchitecture, lymph node metastases, and advanced clinical stage, as compared with diploid carcinomas. Other histologic features predicting aggressive clinical behavior also correlated with abnormal DNA content and included invasion of nerves larger than 0.25 mm and intravascular extension. Our data suggest that DNA content analysis can be an effective objective parameter in the clinicopathologic assessment of adenoid cystic carcinoma.

Adolescent↗

[The relationship between pilocarpine induced autonomic ganglia stimulating activity and salivary secretion of submandibular gland in pithed rat].

Superior cervical ganglion (SCG)-mediated effect of Pilocarpine (pilo.) on salivation of the rat submandibular gland was investigated. A total of 32 SD male rats, aged 12 weeks was divided into 4 experimental groups I to IV. They were anesthetized by pentobarbital (75 mg/kg, i.p.) and tracheotomized to allow artificial respiration. These rats were then ectomized only right SCG, leaving left SCG and injected with pilo. (8 mg./kg, i.v.). Rats of group I which were treated in the manner stated above were used as a control. Rats of group II and IV, of which adrenal glands were removed 18 hr before, were pithed 20 min before the injection of pilo. Rats of group III and IV were administered hexamethonium (C6) (1 mg/kg, i.v.). 5 min before the injection of pilo. Saliva from groups I to IV were collected separately from both salivary glands and flow rate of saliva were measured. Concentration of Na and K were also measured and total amounts of Na and K were calculated. 1) The flow rate induced by pilo. showed a tendency of increase in SCG-ectomized rats. 2) The flow rate showed also a tendency of increase in pithed rats. 3) The concentration and total amount of protein in saliva were decreased by SCG-ectomy. 4) The concentration of K was decreased in only SCG-ectomized rats whereas the total amount of K was closed in group I and II in spite of pithing and/or SCG ectomy. This reduction in K concentration seems to be caused by the increased flow rate as mentioned in paragraph 1). 5) SCG stimulating effect by pilo. was not antagonized, but rather activated by C6. 6) Submandibular ganglion-stimulating effect of pilo. was revealed in group III receiving C6, but this effect was extinguished in pithed rats of group IV. Considering of these results, it is proposed that SCG-stimulating ability of pilo., as shown previously by others, would be caused by activation of M1 receptor, which has sympathetic nerve stimulating effect on salivary glands, and may modify the salivation induced by stimulating effect of pilo. on M2 receptor. Moreover, results obtained with group III suggest that pilo. has submandibular ganglion-stimulating activity, although it's detailed mechanism is unknown.

Animals↗

Movement of horseradish peroxidase in rabbit submandibular glands after ductal injection.

Horseradish peroxidase (HRP) has been used as a tracer to study movements of solutions injected retrogradely via the duct of submandibular glands in rabbits. 0.1 ml of solution was injected either manually or by a constant hydrostatic pressure, and the subsequent distribution of HRP in the gland and duct at different times after injection has been examined histochemically at light and electron microscopical levels. Shortly after the injections, strong interstitial staining for peroxidase resulted from passage between acinar cells. Some sites of cellular uptake were observed and staining occurred in some ductal cells even when the duct had been cut at the hilum to minimize pressure effects. It is not known whether this diffuse uptake represents a physiological or pathological phenomenon. Some interstitial activity still remained 24 hr after injection but had disappeared by 48 hr. Inflammatory cells first appeared in the gland about 4hr after the injection and slowly increased up to about 24 hr after injection. The results indiate that the HRP reaches the interstices of the gland principally by penetration between acinar cells, and that the junctional complexes between striated duct cells appear to be more resistant to disruption by luminal pressures.

Animals↗

Chronotoxicological effect of methyl mercury in rat submandibular gland. Immunohistochemical changes of r-EGF, S-100 protein and keratin.

The effect of toxicity of methyl mercury was investigated in the submandibular gland (SMG) of adult male rats subjected to 12 h light dark cycle (6 a.m. to 6 p.m. light/resting phase; 6 a.m. to 6 p.m. dark/active phase). Two groups of rats received a defined dose of methyl mercury hydroxide at seven different time points during the active (dark) and resting (light) phase over a 24 h period. After 10 d, the rats were killed at 9 a.m. and 9 p.m. in the resting and active phase, respectively. The immunohistochemical distribution pattern of epidermal growth factor (r-EGF), S-100 protein and K8.12 keratin were studied in granular convoluted tubules (GCT). Those rats which received injections during the active phase (6 p.m. to 6 a.m.), showed stronger reactivity for r-EGF; however, the reactivity for S-100 protein was unchanged. On the contrary, in both groups, GCT cells showed intense staining for K8.12 keratin. It is concluded that the detoxification mechanism of mercury appears to be dependent on the chronobiological oscillation pattern of the GCT and their substructures.

Animals↗