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Morphometric studies on the development and sexual dimorphism of the submandibular gland of the mouse.

A light microscopic morphometric analysis of the development of the mouse submandibular gland has been carried out from birth up to the age of 6 weeks. At birth the bulk of the gland consists of approximately equal volume proportions of acinar, terminal tubule and non-secretory cells. The granular convoluted tubule is absent at birth. The neonatal female gland resembles that of the male in many respects. With the regression of the terminal tubule at 2 weeks of age the duct system of the gland is seen to differentiate into excretory, striated and intercalated ducts. The volume proportions of the gland constituents of the female are similar to those of the male at 2 weeks. At this age, the acini occupy 55%, the striated duct 20% and the intercalated duct 15% of the total gland volume. Sexual dimorphism is clearly evident in the gland at 4 weeks of age when the duct system is seen to differentiate to form its granular convoluted tubule component. The granular tubule occupied 19% of the gland volume in the male but only 8% in the female at 4 weeks. The proportions of acini are only 41% in the total gland volume of the male mouse but 62% in the female at 4 weeks. In the male gland the proportions of granular convoluted tubule increase from 13% to 21% between 4 and 6 weeks and the secretory granule content of these cells from 6% to 24%. At 6 weeks of age the volume proportion of granular convoluted tubule in the male is 45% and that in the female is only 12%. At this age the acini occupy a proportion of 30% in the male gland as opposed to 57% in the female gland. At 6 weeks the volume of granular convoluted tubule cells is 40% lower in the female (1842 microns 3) than in the male gland (2995 microns 3).

Animals↗

Proline-rich-protein promoters direct LacZ expression to the granular convoluted tubular cells of the submandibular gland in adult transgenic mice.

The ability of two mouse PRP gene promoters to direct the expression of the bacterial lacZ reporter gene was tested in transgenic mice. Transgenes A1-lacZ and C1-lacZ consisted of 8.2 kb A1 and 7.8 kb C1 PRP promoters respectively fused to the lacZ coding sequence. A1 and C1 are two A-type PRP genes isolated from the inbred SWR mice, which show the same gene structure and similar sequence to the closely related MP2 and M14 PRP genes previously cloned from outbred CD-1 mice. We here show that both A1-lacZ and C1-lacZ transgenes have very similar expression patterns: (1) they expressed the lacZ gene in all 14 established transgenic lines under normal (non-stimulated) conditions; (2) the expression was restricted to the granular convoluted tubular cells of the submandibular glands; (3) the expression was developmentally regulated beginning at sexual maturation and lasting to at least 1.5 years of age; and (4) expression in some lines was probably influenced by sex hormones, since higher expression was found in males than in females. A1-lacZ and C1-lacZ are the first transgenes derived from the PRP/GRP (glutamine/glutamic acid-rich protein) gene superfamily to be expressed in the granular convoluted tubular cells (with known endocrine functions), rather than in the acinar cells (with mainly exocrine functions) of the submandibular glands.

Animals↗

[Sebaceous carcinoma of the submandibular gland: a case report].

Primary sebaceous carcinoma of the major salivary glands is very rare, arising mainly in the parotid. The submandibular gland localization is exceptional and only two cases have been reported in the literature. We report a third case diagnosed in Beaujon's Hospital in a 80 year old woman. Histologically, the tumor was poorly differentiated and lobules contained clear cells, foam cells or adipocyte-like cells, containing lipids stained with Oil Red O. We report the clinical, histological and prognostic features of this rare entity. We also discuss the differential diagnoses that pathologists should discard.

Aged↗

Localization of zinc in the rat submandibular gland and the effect of its deficiency on salivary secretion.

To clarify the role of zinc in the mechanism of salivary secretion, the effects of zinc deficiency on the morphologic findings and secretory function of the salivary gland were investigated with a rat model of chronic zinc deficiency, prepared by feeding a zinc-deficient diet, and a rat model of acute zinc deficiency, prepared by administration of a zinc chelator, dithizone. In rats with chronic zinc deficiency, the granule production in the granular duct cells was decreased, but the glandular epithelial cells and myoepithelial cells showed no degenerative or other destructive morphologic changes. The degranulation of the granular duct cells and acinar cells in response to acetylcholine hydrochloride seen in control rats was strongly inhibited in rats with acute and chronic zinc deficiency. The contractile response of the actin microfilament bundles in the myoepithelial cells to acetylcholine seen in the control rats was also absent in the zinc-deficient rats. Further, electron microscopy of the submandibular gland stained by Timm's method disclosed prominent zinc localization at the membrane surface, granules, and vesicles of the glandular epithelial cells and in the pits of the myoepithelial cells. These findings suggest that zinc, together with many zinc-dependent enzymes, is closely involved in the production and degranulation of secretory granules in the glandular epithelial cells, and also in the contraction of the myoepithelial cells in the submandibular gland.

Acetylcholine↗

Submandibular gland excision: short- and long-term complications.

During a 10-year period, 159 benign submandibular gland excisions were performed in 157 patients. 86 of the patients were available for follow-up evaluation. Both short- and long-term complications were listed. Neurapraxia to the mandibular branch of the facial nerve was frequent after the operation, but restoration of function was seen in 92.3%. Scar problems, sensation changes, reduced salivation and taste perception were noticed by the patients in several cases, but rarely caused dissatisfaction. 18.2% of the patients in the salivary stone group had residual stones in Wharton's duct after the operation. The indication for removal of both glands should be carefully considered because of development of xerostomia.

Adolescent↗

Acute irradiation effects on morphology and function of rat submandibular glands.

In this study the morphologic and functional changes were compared after irradiation (single dose, 15 Gy) of rat submandibular salivary glands. Before and 1-10 days after local irradiation of the gland region, samples of submandibular saliva were collected after stimulation by pilocarpine. At the same time-points and also 3 h postirradiation submandibular glands were carefully extirpated and prepared for histocytologic examination (LM, TEM). Maximal increase of the lag phase and decrease of the flow rate were observed 3 days after irradiation, while [K+] and [Na+] increased and decreased, respectively, from days 1 and 3 after irradiation. Morphologic changes were observed from the third hour after irradiation, were maximal 3 days after irradiation and had partially recovered by day 10. Three hours and 1 day after irradiation degranulation of convoluted granulated tubes (CGT) was observed. Three days after irradiation the most striking morphologic changes in serous and mucous cells were distension of the cisternae of the RER, degeneration of mitochondria and vacuolization of the cytoplasm. Fibril-like condensations of electron dense material in the mucous granules were observed 3 h, 1 and 6 days after irradiation. Regranulation of CGT cells was observed from day 6. From this study it is concluded that changes in salivary gland function can be observed before major morphologic changes occur. Functional changes persist after the morphologic changes seem to have virtually returned to normal.

Animals↗

[Oncocytic adenocarcinoma of the submandibular gland].

BACKGROUND: Malignant oncocytic tumors rarely occur in major salivary glands and generally account for < 1% of all salivary tumors. There is no difference of both sexes and appearing mainly between 50 and 60 years of age. They comprise oncocytes, which are epithelial cells with abnormally formed cytoplasm and acidophilic granular cytoplasma. In the process of the malignant transformation the coexistence from oncocytic rests and untypical oncocytic carcinoma portions can be seen. The tumors show no capsule and an infiltrative local growth with perineural and vascular expansions. PATIENT AND METHOD: A rare case of a 59-year-old man with malignant oncocytoma is presented. The tumor was found in the left submandibular gland with one enlarged lymph node near by. RESULT AND CONCLUSIONS: A general overview of the available literature and the histological classification of oncocytomas is given. Therapy consists of surgical resection and radiotherapy. Close clinical controls are necessary.

Adenocarcinoma↗

Submandibular gland as a site for islet transplantation.

Homologous transplantation of islets of Langerhans into the submandibular glands of Syrian hamsters was successful in 8 out of 10 recipients. The technique was simple and led to formation of islets of various sizes within the parenchyma of the gland. The morphology and endocrine cell patterns of this islets were identical to pancreatic islets. The advantage of this model for islet transplantation is discussed.

Animals↗

[Treatment of xerophthalmia by transplantation of autologous vascularized submandibular gland].

OBJECTIVE: To investigate the feasibility of treatment of xerophthalmia by transplantation of autologous vascularized submandibular gland (SMG). METHODS: The SMGs of 19 patients with severe keratoconjunctivitis were transferred to their temporal region by microsurgery. The arteries and veins of the SMGs were anastomosed to the super-temporal arteries and veins, the SMG ducts were implanted into the conjunctival fornix of the eye. The saliva secreted by the SMG was used as the substitute of tear. RESULTS: The transplantation succeeded in 14 patients and failed in 4. Follow up lastred for 3 months to 2 years. The symptom of corneal xerosis disappeared, the symptoms of photophobia and anemophobia were alleviated, and artificial tear substitutes were not used any more. Epiphora appeared in 4 cases and disappeared after partial resection of the transplanted gland. Atresia of orifice occurred in one case and was cured by reconstruction of the duct. CONCLUSION: Transplantation of autologous vascularized SMG is effective in treating severe keratoconjunctivitis sicca.

Adolescent↗

The ultrastructure of the rabbit submandibular gland.

The secretory granules of the terminal and pre-terminal tracts of the rabbit submandibular gland display distinct features, while the cell morphology is quite similar. Among these cells, some smaller ones presenting an highly dilated endoplasmic reticulum have been identified in the pre-terminal tracts. Some hypothesis have been formulated concerning the function of these cells.

Animals↗

Induction of androgen-dependent protease and serous-like granules by tri-iodothyronine in the submandibular gland of mice with testicular feminization.

Esteroprotease, an androgen-dependent enzyme of the mouse submandibular gland, was increased by injection of tri-iodothyronine (T3) in mice with testicular feminization (Tfm) which are genetically deficient in androgen receptors. Histochemical and electron microscopic studies also demonstrated increases of RNA and serous-like granules in cells of the convoluted tubules of the gland. These findings suggest that the esteroprotease gene in Tfm mice is normal and that T3 can induced both esteroprotease and serous-like granules independently of androgen.

Androgen-Insensitivity Syndrome↗

Distribution of carbonic anhydrase isozyme III (CA-III)-positive cells in duct segments of the bovine submandibular gland.

The distribution of carbonic anhydrase III isozyme (CA-III)-positive cells in bovine submandibular glands was studied by immunohistochemistry. CA-III showed strong immunoreactivity in basal cells and some lining cells of the intercalated ducts as well as in striated and interlobular ducts cells. No significant immunoreactivity could be found in other portions of the glands. Electron microscopically, the immunoreactive basal cells contained scattered tonofibrils in their cytoplasm. The distribution of CA-III suggests that the CA-III-positive basal cells may play a special physiological role, and that they do not only represent undifferentiated lining cells.

Animals↗

[Regeneration of the rat submandibular glands after duct ligation].

The cytomorphologic changes associated with acinar cell recovery in the rat submandibular glands were examined by light and electron microscopic observation and immunohistochemical test using anti-bromodeoxyuridine antibody. Ligation of excretory ducts caused morphological disorganization of the gland parenchyma, with resultant disappearance of the acini, dilation of the ducts, pronounced fibrosis and infiltration of the inflammatory cells. At seven days after obstruction, the acinar cells shrunk and destroyed partly. However, the intercalated duct cells and the myoepithelial cells were unaffected by ligation. Immunohistochemically, bromodeoxyuridine (BrdU) labeled cells existed scatteringly in the original ducts through the period of duct ligation and unligation studied. In the glands after recanalization following 7 days of the duct ligation, the duct-like structures were recognized a progressive increase. There structures were significantly developed in number from 7 to 14 days after the unligation. However, the BrdU-containing nuclei were not almost found in the duct-like structures. At twenty one days after the removal of the obstruction, the regeneration of acinar cells was striking. At 28 days, the acini were almost normal size. In the unligated glands at 21 and 28 days, a variable number of BrdU-positive cells was found in acini. At this stage, the constituent cells of the duct-like structures occurred many vacuoles and a decrease in their secretory granules was marked. These cells were transformed into intercalated duct cells. These results suggest that the constituent cells of the duct-like structures are altered for intercalated duct cells. The regeneration of acinar cells is the result of cell recovery, not the result of de novo cell differentiation.

Animals↗

Evidence for a role of endogenous nerve growth factor in the functional sex difference in the adrenergic innervation of the male and female mouse submandibular gland.

In view of the remarkable sex difference in nerve growth factor (NGF) content in mouse submandibular gland (SMG), a direct comparison of the adrenergic innervation as represented by noradrenaline (NA) content in SMG, rate of losing NA after superior cervical ganglionectomy, post-reserpine recovery of NA and survival and growth of implanted neurons of superior cervical ganglion into SMG was carried out. The results showed that the NA contents in the intact male SMG and in the male SMG during the recovery from reserpinization were higher than those in the female. There were marked sex differences in patterns of the time-course of post-ganglionectomy loss of NA in SMG and in the ability of SMG to support survival and growth of the implanted SCG neurons. These results indicate that NGF in the mouse SMG may play a functional role in the adrenergic neurons innervating the gland.

Adrenergic Fibers↗

Ultrastructure of the acinar cells in the submandibular gland of the nine-banded armadillo.

There are two discrete lobes comprising the armadillo submandibular gland. These two lobes can be defined grossly, histochemically and morphologically with the light and electron microscope. The minor lobe stains more intensely with PAS and AB. When viewed in the electron microscope, the secretory granules of the acinar cells within this lobe appear mucous-like. The granules of the demilune cells are slightly different in appearance. The secretory granules of the acinar cells in the major lobe contain many dense foci embedded in a fibrillar matrix, a substructure not described previously. The demilune cells of this lobe contain secretory granules with a mucous-like structure which is consistent throughout the entire lobe. As in the minor lobe, these demilune cells stain very intensely with PAS and AB.

Animals↗

Cytochemical localization of ouabain-sensitive, K+ -dependent p-nitrophenylphosphatase and Ca++-stimulated adenosine triphosphatase activities in human parotid and submandibular glands.

K+ -dependent p-nitrophenylphosphatase (pNPPase) and Ca++ -stimulated adenosine triphosphatase (ATPase) activities were studied in human parotid and submandibular glands using cytochemical methods at the ultrastructural level. In both glands, only the striated-duct epithelium showed K+ -pNPPase reaction product, thereby indicating the localization of Na+, K+ -ATPase. The precipitate was concentrated on the deep invaginations of the basolateral plasma membranes, in close association with their cytoplasmic surface. Ca++ -ATPase activity was also found on the basolateral plasma membranes, but two striking differences from the K+ -pNPPase distribution were observed: firstly, Ca++ -ATPase appeared in both acinar and ductal cells, and secondly, it was localized on the outer side of the plasma membranes.

4-Nitrophenylphosphatase↗

Isolation and characterization of a mucin-glycoprotein from rat submandibular glands.

A blood group A+ mucin-glycoprotein was purified from aqueous extracts of rat submandibular glands by sequential chromatography on columns of Sepharose CL-6B and Sephacryl S-300 in urea-containing buffers. Final purification was facilitated by reductive methylation which appeared to release contaminating (hydrophobic) peptides. Homogeneity of the purified mucin was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis at varying concentrations of acrylamide, lectin affinity chromatography, and Western blot analysis. In contrast to previously described preparations, the purified mucin contained only trace amounts of N-acetylglucosamine and aromatic amino acids. In addition, only low levels of basic amino acids were present.

ABO Blood-Group System↗

Lectin cytochemistry on developing rat submandibular gland primary cultures.

Lectin cytochemistry was performed in vitro on primary cultures from the rat submandibular gland. For this purpose, prepubertal rats (17, 27, 33 days old) of both sexes were used. Several types of medium supplements were tested and it was found that cells survived until 15 days in presence of all medium supplements and extracellular matrix gel. The binding patterns of all FITC/TRITC-labeled lectins, with and without prior sialidase digestion and deacetylation, were analyzed in a confocal laser scanning microscope. In particular, the occurrence of C4 acetylated sialic acid linked to beta-galactose at day 27 and the presence of fucose residues at day 33 indicated that lectin probes applied to cultured cells give results similar to those obtained in intact tissues and can be used as markers of growth and differentiation.

Acetylglucosamine↗