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Isoprenaline-induced changes in rat parotid and submandibular glands are age- and dosage-dependent.

Neonatal rats treated with chronic injections of isoprenaline (isoproterenol) for 10 days revealed differential induction of proline-rich proteins and glycoprotein synthesis between the parotid and submandibular glands. Biosynthesis of proline-rich proteins (Mr 17000-35000) and a Mr-220000 glycoprotein were detectable by solubilization in 10%-trichloroacetic acid extracts from parotid glands 14 days after birth. The enzyme lactose synthase (UDP-galactose: 2-acetamido-2-deoxy-D-glucosamine 4 beta-galactosyltransferase) (EC 2.4.1.22) is also induced 4-7-fold in specific activity compared with control neonatal rats, but again only after 14 days post partum, with isoprenaline treatment. This is in accord with the ability of the parotid gland to respond to beta-receptor stimulation and subsequent increases in intracellular cyclic AMP necessary for induction of protein synthesis [Grand, Chong & Ryan (1975) Am. J. Physiol. 228, 608-612]. Induction of the proline-rich proteins and a Mr-190000 glycoprotein in the soluble fraction from the submandibular gland were not detected until 49 days after birth under identical conditions in the same animal. Cyclic AMP in the submandibular gland undergoes increases on beta-receptor stimulation similar to those achieved in the adult animal, 1 day after birth (Grand et al., 1975). This same differential induction between parotid and submandibular gland was obtained with a range of isoprenaline dosages in adult animals. Trichloroacetic acid-soluble proline-rich proteins were isolated from parotid glands at a dosage of 4.0 mg of isoprenaline/kg body wt., but 7.0 mg/kg was required to induce also biosynthesis of these proteins in the submandibular gland. Gland hypertrophy showed the same differential dosage kinetics, based on gland weight, between the two glands; however, hypertrophy could be accomplished at a lower dosage of isoprenaline than that used to induce proline-rich-protein biosynthesis.

Age Factors↗

Metastatic tumors to the parotid and submandibular glands--analysis and differential diagnosis of 108 cases.

The distinction between primary salivary gland tumors and metastases of other primary tumors in salivary glands is of special importance for therapy and prognosis. In the files of the Salivary Gland Register, 10,944 cases were collected during 1965 and 1985. Among these cases, there were 108 cases of metastatic tumors to the parotid and submandibular gland. The pathohistological analysis of these tumors revealed the following data: 47 cases (43%) of metastatic tumors were localized in the parenchyma of the parotid gland (37 cases) or of the submandibular gland (10 cases). 61 cases (57%) displayed metastases in the lymph nodes of the parotid gland (38 cases) or of the submandibular gland (23 cases). The sublingual gland was free of metastatic tumors. 65 metastatic tumors originated from primary tumors in the neighborhood (head and neck). 32 tumors were carcinomas of the skin, 17 tumors were melanomas, and 13 tumors were nasopharyngeal cancers. Metastases of thyroid cancers were found in 3 cases. The relative frequency of metastases in the lymph nodes of the salivary glands is due to the intense drainage with lymph vessels and the presence of many lymph nodes which are localized especially in the gland parenchyma or around the parotid gland. 21 metastatic tumors originated from primary tumors distant from the head and neck region. There were metastases of lung cancers (7 cases), renal cancers (6 cases), mammary cancers (6 cases), colonic cancer (1 case) and uterus cancer (1 case). Clear cell carcinomas in salivary gland tissue should always be checked for a metastasis of a primary renal cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Regulation of the level of epidermal growth factor by oestrogen in the submandibular gland of female mice.

The concentration of epidermal growth factor (EGF) in the submandibular gland of immature female mice (less than 6 weeks old) was low, ranging from 0.07 to 0.17 pmol (0.4 to 1.0 ng)/mg wet wt, but increasing to 7.61 pmol/mg wet wt by 8 weeks of age. It remained relatively constant up to 24 weeks of age, but thereafter the glandular EGF concentration increased again during the post-reproductive period to reach 62.9 pmol/mg wet wt. In contrast, the glandular EGF content in male mice increased greatly during the first 17 weeks of age to about 310 pmol/mg wet wt, and thereafter remained relatively constant up to 48 weeks of age. Ovariectomy of mature virgin mice markedly increased the glandular concentration of EGF to about 74.4 pmol/mg wet wt 4 weeks after the operation. This increase was suppressed by oestradiol-17 beta administered to ovariectomized mice at a dose of 1 microgram/mouse per day but not by 1 mg progesterone. Histological studies indicated that granular convoluted tubular cells that produced EGF in the submandibular gland were much less abundant in 12-week-old female and in oestrogen-treated ovariectomized mature mice than in 40-week-old female and ovariectomized mature mice. We conclude that oestrogen suppresses the concentration of EGF in the submandibular gland of female mice.

Aging↗

A preliminary study of the submandibular gland of the rat after one-year cadmium intoxication. Part I. Cadmium concentration.

The aim of the present study was to establish to what degree a one-year exposure of rat females to 5, 50 and 100 mg Cd/l affects the weight of the submandibular glands and their cadmium levels. We observed a decrease in the weight of the submandibular glands in the rat females from Groups I, II and III, compared to the control rats. We also found an increase in cadmium levels in the submandibular glands in Groups I, II and III, in comparison to the control. The highest cadmium concentration was noted in the submandibular glands in Group III, which was accompanied by the greatest weight reduction, the correlation being negative. The present experiment indicates that one-year administration of cadmium to rat females at a dose of 5, 50 and 100 mg Cd/l leads to a cadmium dose-dependent decrease in the weight of the submandibular glands.

Animals↗

The MR imaging assessment of submandibular gland sialoadenitis secondary to sialolithiasis: correlation with CT and histopathologic findings.

BACKGROUND AND PURPOSE: MR imaging has been proved to be effective in depicting wide variety of pathologic changes of the salivary gland. Therefore, we evaluated clinical usefulness of MR imaging for sialolithiasis. METHODS: Sixteen patients with sialolithiasis of the submandibular gland underwent MR imaging. MR images of the glands were obtained with a conventional (T1-weighted), fast spin-echo (fat-suppressed T2-weighted) and short inversion time-inversion recovery sequences. Contrast enhancement was not used. MR imaging features then were compared with clinical symptoms, histopathologic features of excised glands, and CT imaging features. RESULTS: Submandibular glands with sialolithiasis could be classified into three types on the basis of clinical symptoms and MR imaging features of the glands. Type I glands were positive for clinical symptoms and MR imaging abnormalities, and were characterised histopathologically by active inflammation (9 [56%] of 16). Type II glands were negative for clinical symptoms and positive for MR imaging abnormalities (4 [25%] of 16), and the glands were replaced by fat. Type III glands were negative for clinical symptoms and MR imaging abnormalities (3 [19%] of 16). CT features of these glands correlated well with those of MR imaging. CONCLUSION: These results suggest that MR imaging features may reflect chronic and acute obstruction, and a combination of CT and MR imaging may complement each other in examining glands with sialolithiasis.

Adipose Tissue↗

Ultrastructure of the main excretory duct epithelia of the rat parotid and submandibular glands with a review of the literature.

The fine structure of the main excretory duct (MED) epithelia of the rat parotid and submandibular glands was investigated by scanning and transmission electron microscopy. The structure of these two MED epithelia was compared. Five principal cell types were observed in the MED epithelium of the parotid gland--cuboidal, basal, light (types I and II), dark, and tuft cells. The cuboidal cells, which were stratified in two or three layers, were the most numerous. Basal cells were situated adjacent to the basal lamina of the epithelium. The type I light cells had well-developed basal plasma membrane infoldings. The type II light cells had poorly developed basal plasma membrane infoldings. The dark and tuft cells resembled those of the MED epithelium of the rat submandibular gland. Four principal cell types were observed in the MED epithelium of the submandibular gland--light cells (types I and II), dark, tuft, and basal cells. The two types of light cells were the most numerous. Dark cells with regular and dense microvilli were relatively narrow in shape and had complicated basal plasma membrane infoldings. There were numerous vesicles or channel-like vesicles in their apical cytoplasm. Tuft cells were characterized by prominent microvilli, many vesicles of various sizes in the apical cytoplasm, and no basal infoldings. Peroxisomes were present in the MED epithelia of the rat parotid and submandibular glands, especially in light and cuboidal cells.

Animals↗

Immunohistochemical detection of epidermal growth factor in submandibular gland tumours of mice administered testosterone.

Immunohistochemical identification of epidermal growth factor (EGF) is described in experimental carcinoma of the submandibular gland of mice given testosterone before sacrifice. EGF in the submandibular gland was confined to the granular convoluted tubule (GCT) cells, and its level was enhanced following testosterone injection. In the initial phase of carcinogenesis of the gland, degranulation of the GCT cells occurred as well as decreased EGF staining in the degranulated cells. In the testosterone-treated animals, changed GCT cells showed intense EGF deposition. Histological aspects during carcinogenesis in submandibular glands indicated duct-like structures, squamous metaplasia, and squamous cell types of carcinoma with different keratinization. Immunohistochemically detectable EGF was characterized by positive staining in pre-neoplastic or early neoplastic epithelial structures in testosterone-treated mice. However, tumour epithelia did not show any EGF reaction.

Animals↗

Fine structure of the rabbit submandibular gland during the embryonic development.

The development of the submandibular gland has been examined in rabbit embryos from the 22nd day to the birth. The 2 main types of secretory cells, which synthetize dense serous granules or large pale mucous granules can be identified from the 24th day of development. A third type of cells, characterized by granules having different densities, has been identified in the preterminal tracts. The possibility that these cells are similar to some small cell with an highly dilated endoplasmic reticulum found in adult rabbit submandibular glands is discussed.

Animals↗

Explant culture of human submandibular gland epithelial cells: evidence for ductal origin.

As an approach to investigating the disease cystic fibrosis, attempts were undertaken to culture from human submandibular glands epithelial cells with a potential for manifesting the cystic fibrosis genetic defect. To initiate the culture of submandibular gland epithelial cells, tissue fragments from glands were explanted as a function of both the composition of the serum-free growth medium and of the matrix utilized to coat the culture vessel growth surface. A morphologically homogeneous growth of submandibular gland epithelial cells, uncontaminated by fibroblasts, was obtained, once optimum culture conditions were defined. Light microscopic examination of these explant cultures in a transverse plane of section demonstrated variation in the outgrowth according to distance from the explant. At its outer margin, the outgrowth consisted of one or two layers of viable low cuboidal cells, and more centrally, it was multilayered. Mitotic figures were observed in the periphery of the outgrowth. In the region, a few cells removed from the periphery where the outgrowth consisted of about three to six cell layers, dilated intercellular spaces, indicative of secretion of fluid and ions into the spaces, separated the basal cuboidal cells. Overlying cells were increasingly flattened toward the culture surface and devoid of nuclei. Centrally, near the explant, the multilayer appeared completely involuted throughout. Ultrastructural examination in a transverse plane of the multilayered region with viable basal cells confirmed these observations showing wide spaces separating the cuboidal basal cells, keratinization of midstratum cells, and complete involution of the upper layer of ghost-like cells. These cells cultured from the submandibular gland reacted positively to immunochemical staining for keratin.

Cells, Cultured↗

Relationship between epidermal growth factor in mouse submandibular glands, plasma, and bile: effects of catecholamines and fasting.

The epidermal growth factor (EGF) concentration in bile is high (approximately 150 fold higher than that in plasma), but little is known about its physiological control. Acute administration of the alpha 1-adrenergic agonist phenylephrine (1.7 mg/kg, iv) to male mice produced a rapid increase in the EGF concentration in bile. We suggest that this EGF originates in submandibular glands and not in the liver. The bases for this are: 1) this increase was parallel to the increase in plasma, and the EGF content of the submandibular glands decreased after phenylephrine injection; and 2) the EGF concentrations in plasma and bile did not increase after phenylephrine administration to sialoadenalectomized mice. The concentration of EGF in bile is not only under pharmacological control, but is also regulated physiologically. Thus, the EGF concentrations in plasma, bile, and submandibular glands increased in fasted mice. All of these changes were reversed by refeeding. As 1) [125I]EGF binding to liver membranes decreased only after 2 days of fasting, but the level of circulating EGF was already increased in 1-day fasted mice, and 2) EGF secretion by submandibular glands from 1-day fasted mice incubated in vitro increased, we suggest that the increase in EGF concentrations in plasma and bile is the consequence of increased endocrine secretion by submandibular glands. Taken together, our results suggest that there is a flux of EGF from submandibular glands to bile in mice, which is under physiological control.

Animals↗

Immunohistochemical localization of keratin in experimental carcinoma of the mouse submandibular gland.

An immunohistochemical survey of the distribution of keratin was studied in chemically induced carcinomas of the submandibular glands of mice. Initial signs of premalignant changes were degranulation of granular convoluted tubule cells and deposition of keratin protein in small limited areas of the degranulated cells. There was a gradual increase in the area showing keratin staining in altered tubule cells. Duct-like and cystic structures stained intensely for keratin, as did squamous metaplastic epithelial cells. Induced carcinomas were variably keratinized. Basal layers of cells of squamous-cell carcinomas displayed weak keratin staining, and spinous tumor cells and parakeratotic tumor cells showed somewhat increased levels of keratin staining. Some desquamated keratotic tumor cells stained intensely for keratin. Just as the localization of epidermal and nerve growth factors and lectin-binding histochemistry have been used in studying tumorigenesis in the mouse submandibular gland, immunohistochemically detected keratin proved to be a useful marker of tumor cells of ductal segment origin.

9,10-Dimethyl-1,2-benzanthracene↗

Changes in glycoconjugates revealed by lectin staining and stage-specific embryonic antigen-1 immunostaining in hamster submandibular glands during the postnatal period.

Lectin binding and stage-specific embryonic antigen-1 (SSEA-1) immunoreactivity were studied in the developing submandibular glands of young Syrian golden hamsters (Mesocricetus auratus) from postnatal day 1 (the day of birth) to day 28. The submandibular glands were fixed in a solution containing 6% mercuric chloride, 1% sodium acetate, and 0.1% glutaraldehyde (HgCl2-G) or 4% paraformaldehyde (4P), and embedded in paraffin. Sections from HgCl2-G fixation were stained with three lectin-peroxidase conjugates: peanut agglutinin (PNA), Ulex europeus I agglutinin (UEA I), and wheat germ agglutinin (WGA). Sections from the 4P-fixed tissues were immunostained with monoclonal antibodies against SSEA-1, sialyl SSEA-1 and fucosyl SSEA-1. On the day of birth, the terminal unit of the submandibular gland was composed of fetal type secretory cells and proacinar cells. The secretory cells were PNA, UEA I, and WGA positive. The number of secretory terminal tubule cells decreased rapidly, and lectin-positive secretory cells were replaced by adult secretory cells that did not show PNA or UEA I stainings but were weakly positive for WGA. Fetal secretory cells were positively immunostained for SSEA-1 and sialyl SSEA-1, and immature ductal cells were stained for fucosyl SSEA-1. The positive stainings disappeared with regression of the fetal epithelial cells. Hence, modulation of glycoconjugate expression in the submandibular glands, which reflects changes in secretory cells from the fetal type to adult type during postnatal development, is revealed by lectin staining and immunostaining for SSEA-1 and related antigens.

Animals↗

Ultrastructure of the parotid and submandibular glands of the Old World Marten (Carnivora; Mustelidae).

The morphology of the parotid and submandibular glands in the marten, a carnivore, were studied and analyzed under a transmission electron microscope. The nature of the granules in both glands, as well as in the acini and in the secretory tubules, is rather mucous. The structure of the secretory tubules is very characteristic, especially the striated ones. The myoepithelial cells are close to the acini and tubules and covered by the basement membrane separating them from the connective tissue, which enhances its epithelial origin. The cytoplasm of the basal parts of the acinar and tubular cells is abundant and separates the nucleus from the secretion granules. Although the morphology of the salivary glands of many carnivores is known, those of the parotid gland of the marten present peculiar characteristics, since they produce a rather mucous saliva and the granules, when forming, are far from the base as well as from the apex of the secretory cells. The submandibular gland contains granules of different densities, an aspect that in general resembles that of other animals.

Animals↗

Localization of kallikrein and its relation to other trypsin-like esterases in the rat pancreas. A comparison with the submandibular gland.

Kallikrein was located by the direct immunofluorescence technique to the granule-containing luminal portion of pancreatic acinar cells. For the demonstration of the intracellular distribution of pancreas kallikrein, in vivo fixation of the gland was necessary. No kallikrein was found in the duct cells or in the islets of Langerhans. Quantitation by single radial immunodiffusion showed that the concentration of kallikrein in the presence was 1.32 +/- 51 microgram/g wet weight, i.e. 1/91 that of the rat submandibular gland. Bz-Arg-OEt-esterases were in the pancreas found as pro-enzyme but as active enzyme in the submandibular gland. Trypsin-like esterases, hydrolyzing epsilon-amino caproic acid naphtol-AS-D.HBr (ACA), were found in the active form in both submandibular gland and pancreatic homogenates. The submandibular gland contained per g wet weight 6 times as much ACA-esterase activity as the pancreas. In the submandibular gland, kallikrein and ACA-esterase activity were found together in practically all granular tubular cells. Thus, the granular tubular cell contains kallikrein as well as other trypsin-like enzymes like the ACA-esterase, and is in this way comparable to the pancreatic acinar cell. An extraglandular function of kallikrein is suggested for the pancreas in contrast to other kallikrein-containing exocrine organs.

Animals↗

Transport of calcium in the perfused submandibular gland of the cat.

1. In the perfused cat submandibular gland efflux and influx of (45)Ca, and concentrations of K, (40)Ca and Mg in the effluent from the gland were measured under different experimental conditions.2. When the standard perfusion fluid was shifted to a high Mg (5 mM) or a low Ca (0.25 mM) solution the efflux of (45)Ca from the pre-labelled gland declined. The magnitude and the duration of the effect of the high Mg concentration was more marked at a low external Ca concentration and was abolished by Mersalyl (1 mM). When the standard perfusion fluid was shifted to a Mg-free solution the efflux of (45)Ca from the pre-labelled gland increased.3. After shift of (45)Ca containing perfusion fluid from normal to a high Mg (5 mM) solution the influx of (45)Ca to the gland increased rapidly.4. Both acetylcholine (ACh) and adrenaline caused a marked increase in the efflux of (45)Ca from the pre-labelled gland. This increase in efflux was also seen under conditions where the gland was unable to secrete, i.e. during perfusion with Ca-free and Na-free tetraethylammonium Locke solutions.5. Stimulation with ACh failed to reveal any rapidly occurring increase in influx of (45)Ca.6. Stimulation with ACh evoked a small temporary increase in the concentration of (40)Ca. and Mg in the effluent.7. It is suggested that Ca uptake by intracellular Ca-accumulating systems of the submandibular gland depends on the external Mg concentration and that ACh and adrenaline cause a release of Ca bound intracellularly.

Acetylcholine↗

Evidence that aquaporin-8 is located in the basolateral membrane of rat submandibular gland acinar cells.

It is possible that, during primary saliva formation, aquaporins (AQPs) facilitate transcellular water flow across acinar cells to the lumina of salivary glands. In the rat submandibular gland (rSMG) AQP5 is localized in the apical membranes of acinar cells. The presence of a basolateral AQP in the same cell type has not been reported. We have therefore used immunofluorescence confocal microscopy to determine the subcellular localization of a newly discovered aquaporin, AQP8, in rSMG epithelial cells. The antibodies we used were made against the amino- or carboxyl-terminus (anti-rAQP8NT and anti-rAQP8CT, respectively) of an AQP8 cloned from rat pancreas and liver (rAQP8). Two lines of evidence suggest that both antibodies are suitable for immunolocalization studies. First, results of immunofluorescence confocal microscopy studies show that both antibodies bind to the plasma membranes of 293 cells infected with an adenovirus encoding rAQP8. Second, results of immunoblots of membranes from infected cells suggest that both antibodies bind to glycosylated and non-glycosylated forms of rAQP8. When tested in frozen sections of rSMG, we could not detect the binding of anti-rAQP8NT to any membranes. In contrast, anti-rAQP8CT binds to the basolateral membranes of acinar (but not ductal) epithelia, suggesting that rAQP8 resides in the basolateral membranes of acinar cells. Lack of anti-rAQPNT binding to basolateral membranes suggests that this epitope is not available in the membranes. Our evidence for the basolateral localization of rAQP8 in acinar cells, coupled with previous findings that AQP5 is localized apically in the same cells, raises the possibility that water crosses the acinar epithelium through these channels during primary saliva formation.

Animals↗

Removal of the submandibular gland by a retroauricular approach.

OBJECTIVE: To evaluate the benefit of a retroauricular approach by comparing it with a conventional transcervical approach for removal of the submandibular gland. DESIGN: Prospective clinical study. SETTING: Academic center. PATIENTS: Thirty patients with benign submandibular gland disorders. INTERVENTIONS: Patients were divided into 2 surgical groups to undergo retroauricular (n = 15) and conventional (n = 15) procedures matched by age, sex, marital status, and pathologic condition. The retroauricular approach used an incision along the postauricular sulcus and hairline and subcutaneous tunneling to the gland; the conventional approach used an incision along a natural skin crease overlying the gland. MAIN OUTCOME MEASURES: The operation time, complications, hospital stay, and subjective satisfaction of incision scar checked by visual analog scale were compared between groups. RESULTS: The submandibular gland disorders were comparable between groups: pleomorphic adenoma (n = 15), chronic sialadenitis with sialolithiasis in the gland (n = 5) or hilum (n = 8), and Küttner (n = 1) or Kimura (n = 1) disease. Mean +/- SD operation times were 49 +/- 17 minutes in the retroauricular group and 38 +/- 15 minutes in the controls (P = .08). Mean +/- SD hospital stay and complication rates were comparable between groups. The mean +/- SD score of patient satisfaction was 8.9 +/- 0.9 in the retroauricular group and 4.2 +/- 2.9 in the conventional group (P<.001). The incision scar was commonly less visible in the retroauricular group because of hiding by the auricle and natural hair when comparing with the control group. CONCLUSION: The retroauricular approach can provide better cosmetic outcome than the conventional transcervical approach and without significant complications.

Adolescent↗

Peroxidase activity in the submandibular gland of the house musk shrew, Suncus murinus (Soricidae, Insectivora).

Endogenous peroxidase activity in the submandibular gland of the house musk shrew, Suncus murinus was cytochemically investigated by light and electron microscopy using 3,3'-diaminobenzidine-tetrahydrochloride salt (DAB). The submandibular glands of male Suncus murinus at 8-month-olds were excised and diced into small pieces. In general, salivary glands are structurally divided into a terminal portion comprising a secretory portion and duct system. The submandibular gland of the Suncus murinus, the terminal portions consisted of proximal and distal acinar cells. On the other hand, a granular duct cell of the duct system contained a number of characteristic myelin-like bodies. In the present study, the peroxidase reaction products were localized in the secretory granules of the proximal acinar cells and in the endoplasmic reticulum, Golgi apparatus and myelin-like bodies of the granular duct cells. These reaction products were reduced when 5 mM 3-amino-1,2,4-triazole was added to the reaction medium. Additionally, release of peroxidase into the lumen was observed. In conclusion, the proximal acinar and granular duct cells formed peroxidase and may have performed excretory secretions. Moreover, the peroxidase positive myelin-like body consisted of lamellated membrane and its outer surface membrane continued to the endoplasmic reticulum.

Animals↗