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True malignant mixed tumor of the submandibular gland.

A case of true malignant mixed tumor of the submandibular gland is reported. The submandibular tumor, occurring in a 52-year-old man, started to grow rapidly after a long history without any change in size. Surgical resection was carried out and the resected tumor measured 5.5 cm with a cut surface showing mixed solid structures. Microscopically, the tumor had both carcinomatous and sarcomatous elements, the former consisting of poorly differentiated adenocarcinoma with squamous cell differentiation and the latter consisting of osteosarcoma with chondrosarcomatous and fibrosarcomatous elements. A remnant of benign pleomorphic adenoma could also be identified. Immunohistochemical study demonstrated keratin and epithelial membrane antigen in the carcinoma cells and vimentin in all elements of the osteosarcoma. It is assumed from these clinical and histological findings that the tumor had transformed from a pre-existing benign pleomorphic adenoma.

Adenoma, Pleomorphic↗

Handling of calcium by the ferret submandibular gland.

The handling of Ca by the submandibular gland of the ferret during stimulation of salivation with pilocarpine was studied using micropuncture and microanalytical, as well as standard, physiological techniques. Concentrations of ionized Ca were measured in the fluid from the intercalated, lobular, and main ducts of the gland. The net transductal fluxes of this divalent ion were calculated.

Animals↗

Sebaceous carcinoma of the submandibular gland with high-grade malignancy: report of a case.

A case of sebaceous carcinoma arising in the left submandibular gland of a 66-year-old man is reported. The clinical and pathological examinations revealed a carcinoma, which was to salivary gland in origin, with regional lymph nodal metastases. Pathological findings showed features of high-grade sebaceous carcinoma with spindle myoepitheliomatous differentiation. Neither squamous cell nor duct epithelial-like cell differentiation was noted. Immunohistochemically, tumor cells were positive for cytokeratin, S-100 protein and vimentin. Lipid was demonstrated in the cytoplasm of the tumor cells. Ultrastructurally, tumor cells contained numerous intracytoplasmic lipid droplets. Myoepitheliomatous differentiation is rare in sebaceous carcinoma of the salivary gland. Presented is the second reported case of sebaceous carcinoma arising in the submandibular gland.

Aged↗

Fine structural localization of acetylcholinesterase activity in rat submandibular gland.

Using the indirect thiocholine method, the ultrastructural localization of acetylcholinesterase (AChE) activity in the normal rat submandibular gland was studied. Cytochemical demonstration of AChE is based on coupling the hydrolysis of acetylthiocholine iodide to the precipitation of heavy metal salts. AChE-associated reaction product was selectively revealed in the perinuclear space and in the endoplasmic reticulum of the intercalated duct cells, in some cells of granular convoluted tubules, and in the striated duct epithelium, as well as in the myoepithelial cells. Although AChE activity generally occurred inside the cells, electron-dense precipitates were shown in intercellular space and in the stroma of the gland. Fine localization of AChE activity was also found in nerve bundles, predominantly between axons and between axons and Schwann cell. Our observations indicate that AChE is synthesized in the epithelium of the ducts and in the myoepithelial cells of the salivary gland. It is not known yet whether this enzyme is released from the intracytoplasmic membrane system into the extracellular space and then transported to the regions of the gland innervation. Conceivably AChE synthesized in the submandibular gland cells could also be considered an inhibitory modulator of the regulatory functions of biologically active polypeptides.

Acetylcholinesterase↗

The metabolism of O-acyl-N-acylneuraminic acids. Biosynthesis of O-acylated sialic acids in bovine and equine submandibular glands.

1. The enzymic synthesis of 4-O-acetylneuraminic acid, 4-O-acetyl-N-glycolyneuraminic acid, 4-O-glycolyl-N-acetylneuraminic acid, 9-O-acetyl-N-acetylneuraminic acid and 9-O-acetyl-N-glycolyneuraminic acid is shown using radioactive precursors with surviving slices, membrane fractions or particle-free homogenates from bovine and equine submandibular glands. 2. Acetyl-CoA: N-acetylneuraminate-9(or 7)-O-acetyltransferase activity was found in a microsome fraction and in the cytosol of bovine submandibular glands. The properties of the membrane-bound enzyme acting on endogenous, glycoprotein-bound N-acetyl- and N-glycolylneuraminic acids were compared with those of the soluble enzyme, O-acetylating exogenous, non-glycosidically bound N-acetyl- and N-glycolyneuraminic acids. 3. A rapid, radioactive assay for the membrane-bound enzyme activity is described. The enzyme activity shows an optimum at pH 7 and has a Km for acetyl-CoA of 0.1 mM. The enzyme is inhibited by p-chloromercuribenzoate and iodoacetate. Divalent cations, EDTA and glutathione have no influence on its activity while CoA proved to be a competitive inhibitor with a Ki of 0.56 mM. 4. The soluble enzyme activity, assayed using a radioactive procedure, shows Km values of 0.01 mM, 0.5 mM and 0.39 mM for acetyl-CoA, N-acetylneuraminic acid and N-glycolylneuraminic acid respectively. The general properties are similar to those found for the membrane-bound enzyme, except that membrane-bound activity is stable for longer on storage at 4 degrees C. 5. Acetyl-CoA, acyl-CoA and CoA concentrations of 33 nmol, 65 nmol and 106 nmol/g wet tissue respectively are found in fresh bovine submandibular glands. 6. The occurrence of the CMP-glycosides of N-acetylneuraminic acid, 9-O-acetyl-N-acetyl-neuraminic acid and N-glycolylneuraminic acid in bovine submandibular glands is demonstrated. 7. The results are discussed in relation to the general metabolism of acylneuraminic acids.

Acetyltransferases↗

Increasing frequency of occurrence of tuft cells in the main excretory duct during postnatal development of the rat submandibular gland.

Tuft cells, a widespread cell type that is present in the mucosal epithelia of hollow organs, including the main excretory duct (MED) epithelia of the rat salivary gland, are well documented morphologically. However, studies of their development are few. The purpose of the present study was to examine the perinatal and postnatal development of tuft cells in the main excretory duct of the rat submandibular gland. Main excretory ducts of the submandibular gland were obtained from five male Wistar rats at the ages of 0, 1, 7, 14, 17, 21, 23, 28, and 56 postnatal days and were prepared for scanning and transmission electron microscopy. The tuft cells, which are distinguished easily by their long microvilli protruding into the lumen, were recognizable first at 17 postnatal days. They showed a remarkable increase in number between 3 and 4 postnatal weeks. The percentages of tuft cells were 0.4% at 17 postnatal days and 0.8% at 3 postnatal weeks. The number of tuft cells represented approximately 5% of the total epithelial cells by 4 postnatal weeks. There was a significant difference between 3 and 4 postnatal weeks (P < 0.01). The microvilli of the tuft cells at the time of weaning had almost the same width as in the adult, but they were shorter. Microfilaments extending from the tips of the microvilli and microtubules and many electron-lucent vesicles in the supranuclear cytoplasm also were observed. These results indicate that tuft cells appeared in the MED of the submandibular gland during weaning and had abundant vesicles in their apical cytoplasm.

Animals↗

Effects of acute and long-term atropine treatment on levels, release and response to VIP and PHI in the submandibular gland of cat and rat.

We have studied the effects of acute and long-term treatment of cats and rats with atropine on the levels, release and effects of two peptides, vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI), that probably co-exist with acetylcholine in the parasympathetic nerves supplying the submandibular gland. Atropine treatment (progressively increasing doses from 2 to 15 mg kg-1 injected s.c.) for 14 days did not alter the contents of VIP- or PHI-like immunoreactivity (-IR) in the cat submandibular gland or in three other tissues (nasal mucosa, trachea and tongue). Acute as well as long-term atropine treatment decreased the vasodilation following low-, but not high-, frequency parasympathetic nerve stimulation. During prolonged stimulation (60 min) there was a decreased vasodilatation response following both acute and long-term atropine treatment. The overflow of VIP-IR and PHI-IR following parasympathetic nerve stimulation was markedly increased by acute, but not by long-term atropine treatment. The VIP- or PHI-induced stimulation of cyclic AMP (cAMP) accumulation in the cat submandibular gland was not altered after long-term atropine treatment. Similarly, treatment of male Sprague-Dawley rats with atropine (20 mg kg-1) or imipramine (20 mg kg-1) for 14 days did not alter the sensitivity to VIP or to PHI of cAMP accumulation in the submandibular gland, nor was there any change in VIP-IR or PHI-IR content. In conclusion, although atropine treatment causes an acute increase in the overflow of VIP and PHI evoked by parasympathetic nerve stimulation, there is no depletion of peptide stores upon long-term treatment, nor is there any change in the effect of exogenous VIP and PHI on cAMP-accumulation.

Adenylyl Cyclases↗

Epidermal growth factor secretion by submandibular glands is not perturbed in the early phase of streptozotocin-induced diabetes in mice.

In rodents, diabetes mellitus is accompanied by a decreased concentration of epidermal growth factor (EGF) in plasma and urine and by a reduced number of EGF receptors on the surface of target cells. A combination of these two abnormalities may reduce the effects of EGF and could be implicated in some complications of diabetes. The aim of the present work was to investigate the possible implication of the major source of EGF in the organism, the submandibular glands, upon the reduced EGF concentration in blood and urine. Firstly, we measured the content of mice submandibular gland EGF by radioimmunoassay and by morphometric determinations of the relative volume occupied by granular convoluted tubules in the gland and by the EGF-containing granules in the cells at the light and electron microscopical levels respectively. We found no differences in the EGF content of submandibular glands of streptozotocin-treated diabetic animals compared to control ones. Secondly, we estimated stimulus-secretion coupling by EGF-secreting cells, present in an enriched preparation of granular convoluted tubules (GCT) perifused in thermoregulated chambers. Phenylephrine was the only agent tested that was capable of stimulating EGF secretion. The stimulation was dose-dependent and similar in streptozotocin-diabetic and control mice. Thus, the EGF deficiency observed in diabetic mice is related neither to a defect of EGF content in the submandibular glands nor to an abnormal EGF secretion by the glands.

Animals↗

Plexiform neurofibroma of the submandibular gland.

A rare plexiform neurofibroma of the submandibular gland in a patient with neurofibromatosis is presented. The clinical manifestations of the disease are reviewed. The need for early diagnosis of neurofibroma is emphasized because of malignant transformation.

Adult↗

Continuous measurements of tissue impedance during secretion in dog submandibular gland.

The electrical impedance of the dog submandibular gland, as an indicator of changes in extracellular fluid (ECF) volume, was measured at 5 kHz, 500 kHz, and 5 MHz at intervals of 10 s during secretory stimulation, because the conductivity calculated from impedance at low frequencies reflected the ECF volume. The decrease in conductivity occurred in the first minute of stimulation. Its decrease was more marked during stimulation after circulatory arrest. Salivary secretion under intact circulation consists of two phases: an initial secretion occurring in the first minute of stimulation with a high secretory rate and a steady secretion continuing during stimulation at a constant rate. A decrease in conductivity occurred in the initial secretion. Within a few minutes following the cessation of stimulation, the conductivity increased to a level higher than the resting one with an intact circulation, while the blood flow remained several times higher than in the resting state. The conductivity of the gland slowly recovered to the prestimulation level over a 30-min period. The histological examination revealed that the main compartment of the ECF change was the interlobular space. Impedance and histological studies showed that the ECF volume of salivary glands changes dynamically during secretion. On the other hand, the cellular volume also increased in the initial secretion of an isolated gland. Its increase suggested that the fluid was transported to the lumen via a cellular pathway as well as a paracellular pathway in the initial secretion.

Animals↗

Immunohistochemical demonstration of epidermal growth factor and nerve growth factor in experimental carcinogenesis in the mouse submandibular gland.

Immunohistochemical demonstration of epidermal growth factor (EGF) and nerve growth factor (NGF) was made during chemical carcinogenesis in the mouse submandibular gland. The granular convoluted tubule cells in the normal male submandibular gland contained larger amounts of EGF and NGF than in the female. The initial phase and early stages in chemical carcinogenesis showed degranulation of the granular convoluted tubule cells with a marked decrease in EGF and NGF. Premalignant lesions such as duct-like structures and multicystic lesions showed variable staining for EGF and were usually negative for NGF. Material secreted into the luminal spaces revealed increased staining for EGF and NGF. Scattered tumor cells of the poorly differentiated squamous-cell carcinoma type and desquamated tumor cells contained abundant EGF, but not NGF. No positive reaction for EGF or NGF was found in the induced squamous-cell carcinoma cells.

Animals↗

Volume-weighted mean volume of the submandibular gland acini in male and female diabetic rats.

Mouth dryness is one of the complications of diabetes mellitus but there has been little work on morphological changes of the salivary glands. In the present study, the effects of diabetes mellitus on the serous and mucous acini of submandibular gland of male and female rats, 4 and 12 weeks after diabetes induction were studied. Male and female rats were divided into experimental and control subgroups. Diabetes was induced to experimental rats by streptozotocin. At the end of 4 and 12 weeks, the submandibular glands were removed, random sections obtained and volume-weighted mean acini volume was estimated by point-sampled intercepts method. The data revealed that volume reduction occurred only in serous acini in both male and female rats 12 weeks after diabetes induction and the others remained unchanged. The present research using stereological methods demonstrates that diabetes make some morphological changes in serous acini, the main exocrine part of the rat submandibular gland.

Animals↗

Growth pattern of experimental squamous cell carcinoma in rat submandibular glands--an immunohistochemical evaluation.

Histopathological and immunohistochemical studies during carcinogenesis in rat submandibular glands (SMGs) using a carcinogen (9,10-dimethyl-1,2-benzanthracene: DMBA) were evaluated. For carcinogenesis, the carcinogen-containing sponge was surgically inserted into the gland. Histopathological features during carcinogenesis were as follows; dilatation of ductal segments, the presence of duct-like structures and cystic lesion around the sponge were observed within 3 weeks of the experiment, squamous metaplasia in duct-like structures and lining epithelium of the cystic structures around the sponge were observed at 4-6 weeks of the experiment, and finally well differentiated squamous cell carcinomas (SCCs) were observed after 8 weeks of the experiment. The immunoreactivity of K8.12 keration (K8.12), S-100 protein (S-100), epidermal growth factor (EGF), laminin, and proliferating cell nuclear antigen (PCNA) were evaluated. In the normal SMG, EGF was confined to the granular cells and S-100 to the pillar cells of granular convoluted tubules (GCTs). K8.12 was found in striated (SD) and excretory duct (ED) cells and laminin showed linear staining of the basement membrane around the ducts, acini and blood vessels. PCNA-positive nuclei were rarely observed in the normal glandular parenchyma. During carcinogenesis, during the first stage, EGF in granular cells and S-100 in pillar cells of GCT segments disappeared, and cytokeration K8.12 was observed in duct-like structures and cystic epithelium around the DMBA sponge. PCNA-positive nuclei in the first stage were mainly confined to basal cells of morphologically altered ducts. During the second stage, squamous metaplastic cells showed an intense K8.12 reaction. During the third stage, the well differentiated SCC showed strong reaction for K8.12, and the linear staining for laminin staining had disappeared at the invading fronts. The PCNA index was nearly 40% in the tumour cell component. The stem cells or the progenitor cells during experimental carcinoma were most likely to be the ductal basal cells, and carcinogenesis was initiated with an increase of proliferating activity in small cell clusters surrounding a necrotic area, basal cells of dilated excretory ducts and duct-like structures. Thus, all ductal segments undergoing squamous metaplasia may participate in the genesis of neoplasia during experimental carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Prenatal development of the human submandibular gland.

The prenatal development of the human submandibular gland has been investigated in 26 fetuses from the 10th week of gestation to full term. At 10-12 weeks, the glandular elements (primitive ducts and acini) were immature and surrounded by a loose mesenchyme. The acinar cell population increased gradually till the age of 32 weeks, and the rate of increase was diminished thereafter. At 16 weeks, intercalated and striated ducts were distinguished and their number increased till the age of 32 weeks when their number seemed to be stabilized. The development of the granular convoluted tubule cells from the proximal segments of striated ducts occupied the later stages of development. They appeared around the age of 20 weeks and proceeded till full term. At birth, the gland appeared devoid of mucous acini and fat cells and the secretory end-pieces were of the serous type. During the second trimester, periodic acid-Schiff- and alcian blue-positive secretory materials appeared in the epithelial cells of both ducts and acini, and in their lumina. This secretory activity was transitory and disappeared around the age of 28 weeks. The possible function of these secretory products is discussed.

Cytoplasm↗

Androgenic regulation of N-acetyl beta-glucosaminidase activity in the submandibular glands of mice.

N-Acetyl beta-glucosaminidase [beta-2-acetamido-2-deoxy-D-glucoside acetylamido-deoxyglucohydrolase; EC 3.2.1.30] in the submandibular gland of mice was found to be androgen-dependent; the specific activities in males, females, and castrated males were 0.25, 0.11, and 0.11 unit/mg protein, respectively. The activities in females and castrated males were increased to the level of normal male mice by testosterone injection. Injections of progesterone and 17 beta-estradiol hardly affected the activity in males. In both males and females, the enzyme activity was detected in the convoluted tubular cells, not in acinous cells. The results of isoelectric focusing have shown that one enzyme having an isoelectric point of 9.0 is present in the glands of both sexes, indicating that the enzyme remains after castration and that the increases caused by testosterone represent the same molecular species. In addition, it was shown that the saliva from both sexes contained significant activity of N-acetyl beta-glucosaminidase, which also changed depending on the androgenic state of the animals. Most of the salivary activity was shown to originate from the submandibular gland, since the extirpation of this gland resulted in a significant decrease of the salivary activity.

Acetylglucosaminidase↗

[Necrotizing sialometaplasia of the submandibular gland. Report of a case].

A case report of swelling of the right submandibular gland, with spontaneous remission, is described. Clinical, ultrasonographical and cytological features suggest that the swelling could be ascribed to a necrotizing sialometaplasia. The etiopathological hypothesis and pathology of the lesion are presented, and the differential diagnosis with other spreading lesions of the submandibular gland is discussed.

Aged↗

Structural and cytochemical observations in the submandibular gland of unweaned cats.

An investigation by electron microscope was performed on the submandibular gland of unweaned cats for studying its morphology and carbohydrate histochemistry. The cytoarchitecture was comparable with that of adult animals with the exception of the degree of membrane merging in both demilunar and acinar cell secretory granules. Conversely, the submandibular gland of unweaned cats showed a peculiar HID-TCH-SP reactivity at acinar cell level.

Animals↗