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[Necrotizing sialometaplasia (salivary gland infarct) of the submandibular gland. A case report].

Necrotizing sialometaplasia, being a rare, nonspecific reaction to ischaemic injury in salivary gland tissues of the head, is discussed in connection with a case of our own. In contrast to former reports concerning such lesions above all in minor salivary glands the following report concentrates on a case of necrotizing sialometaplasia in the submaxillary salivary gland of a 57-year old woman who noticed after exstirpation of a pleomorphic adenoma in the submaxillary gland a swelling that presented histologically as necrotizing sialometaplasia. Emphasis is placed on a detailed morphological knowledge of this innocuous, self-repairing process, since the extensive squamous cell metaplasia of minor excretory ducts as the essential finding could be easily misdiagnosed as a squamous cell carcinoma and, therefore deserves special consideration in differential diagnosis of salivary gland tumours.

Adenoma, Pleomorphic↗

Morphology and histochemistry of rabbit submandibular glands.

The rabbit submandibular glands are of the heterocrine type. The most distal part of the ductal system consists of secretory endpieces, which are constructed mainly of two morphologically and histochemically different and distinct structures: distally the seromucous acini and proximally the serous tubuli. The cells of the seromucous acini are strongly AB pH 2.5 positive, AB pH 1.0 negative and PAS negative, indicating production of acid glycoproteins--mainly sialomucin. The cells of the serous tubuli are AB pH 2.5 negative and strongly PAS positive, indicating the presence of neutral glycoproteins. Glycol methacrylate embedded sections (Historesin) stained with a modified Trichrome stain were superior to standard paraffin sections regarding resolution and clarity of morphological details. Quantitative studies of intralobular structures on AB-PAS-stained paraffin sections compared with Trichrome-stained glycol methacrylate sections gave corresponding results. The latter method is well suited for study of structural changes in submandibular glands, as in assessing the effect of ionizing irradiation.

Animals↗

A simple and rapid purification of kallikrein from rat submandibular gland.

Rat submandibular kallikrein was isolated in an 87% yield by a very quick and simple procedure involving hydrophobic interaction chromatography. Furthermore, that purification method was superior to both aprotinin-affinity chromatography and immunoaffinity chromatography for the purification of rat submandibular kallikrein. The kallikrein purified by hydrophobic interaction chromatography consisted of a number of isoenzymes. The major component of Mr 38,000 seen on SDS-gel electrophoresis was found to be the glycosylated kallikrein, whereas the minor component of Mr 26,000 represented the non-glycosylated enzyme.

Animals↗

Malignant salivary gland tumors: squamous cell carcinoma of the submandibular gland in a child.

PURPOSE: Malignant neoplasms of the salivary glands are extremely unusual in the pediatric age group. METHODS: We report an 11-year-old boy who presented with a mass in the left submandibular region and a second mass in the jugularfacial venous angle. RESULTS: Histologic evaluation determined that this was a squamous cell carcinoma of the submandibular gland with metastasis to a cervical node. Review of the literature was undertaken to identify the rate of malignant salivary gland tumors in children. Malignant salivary gland tumors are extremely rare in children. When malignancy does occur, nearly 90% are present in the parotid gland. The submandibular gland is effected in 7.7% of cases. The most common malignancy in salivary glands of children is the mucoepidermoid carcinoma. Squamous cell carcinoma occurs in less than 2% of cases. CONCLUSIONS: Salivary gland tumors are very rare in children in contrast to adults. The proportion of malignant tumors in children is higher than that observed in adults; however, it is not possible to draw conclusions concerning treatment from the few case reports that exist. A higher rate of local recurrence and cervical lymph node metastasis may be expected in children.

Carcinoma, Squamous Cell↗

Effect of sympathetic innervation on isoproterenol-induced cystatin S gene expression in rat submandibular glands during early development.

The rat submandibular gland is innervated by both sympathetic and parasympathetic branches of the autonomic nervous system which, in turn, regulate the secretory function of the gland. Parasympathetic innervation of rat submandibular glands is present at birth; in contrast, sympathetic innervation reaches the glands by postnatal day 5. Isoproterenol (IPR), a beta-adrenoreceptor agonist, induces hypertrophic and hyperplastic enlargement of rat salivary glands, and induces the expression of a number of genes, including cystatin S (Cys S), a member of family 2 of the cysteine proteinase inhibitor superfamily. Cys S gene expression is tissue specific, cell type specific, occurs temporally during normal development and is not observed in adult animals unless stimulated by IPR. In addition, sympathectomy of adult rat submandibular glands reduced IPR-induced expression of the Cys S gene. This paper reports experiments analyzing the participation of the sympathetic branch of the autonomic nervous system in IPR-induced expression of the cystatin S gene during early development of the submandibular gland. The rat Cys S gene could be induced by IPR by day 3, and the level of Cys S mRNA remained constant until 8 days at which time a dramatic IPR induction of Cys S mRNA was observed. This statistically significant increase in Cys S mRNA at 8 days was diminished, but not completely suppressed, upon sympathectomy of 1-day-old animals. These data indicate that an intact sympathetic innervation is not a requisite for IPR-induced Cys S gene expression in developing submandibular glands; however, sympathetic innervation is required for the full IPR response of the Cys S gene in developing submandibular glands. The developmental experiments presented in this paper indicate that factor(s) coming from the sympathetic nervous system participate in IPR-induced expression of the Cys S gene in rat submandibular glands.

Adrenergic beta-Agonists↗

[Submandibular gland excision. Clinical experience].

Submandibular gland excision is proposed for the treatment of both neoplastic and non-neoplastic diseases. This study examines four cases of patients who underwent submandibular gland excision performed by the transcervical approach: two cases of non-neoplastic disease (one sialolithiasis and one chronic sialoadenitis not correctly assessed by sonography), one case treated for chronic sialoadenitis who developed a non-Hodgkin lymphoma involving the oral mucosa, and one case with a benign neoplastic lesion (pleomorphic adenoma). The symptoms, physical findings, and diagnosis on pathological examination are discussed in each case. On the basis of the literature, the indications for submandibular transcervical excision and the postoperative neurological complications are discussed, emphasising that only a detailed knowledge of the anatomy of the region can reduce the morbidity of this operation.

Female↗

Cell differentiation in the terminal tubule of fetal rat submandibular gland in organ culture.

Submandibular glands from 17-day-old rat fetuses were maintained in organ culture for five days in a medium consisting of Eagle's MEM (87%), horse serum (10%), and chick embryo extract (3%). Each day of the culture period explants were incubated for the demonstration of peroxidase activity and processed for light and electron microscopic observations. In some experiments cultures were exposed to 3H-thymidine one hour prior to fixation and incubation for the demonstration of peroxidase activity. Labelling index was determined using radioautographs of 1 mu Epon-embedded sections. At the time of explantation the submandibular gland rudiment consisted of undifferentiated epithelial cells arranged in cords. On day 3 of culture two additional cell types could be distinguished: terminal tubule cells and proacinar cells. The proacinar cells were characterized by peroxidase activity in their granules and cytoplasm. By day 4 acinar cells begin to appear. On the fifth day of culture the four cell types of the terminal tubule were present in the following proportions: undifferentiated cells, 44%; terminal tubule cells, 19%; proacinar cells, 31%; acinar cells, 6%. These results indicate that the cytodifferentiation of the secretory unit of rat submandibular gland in vitro is comparable to the differentiation in vivo.

Animals↗

Immunolocalization of fibroblast growth factor-2 (FGF-2) during embryonic development of the rat submandibular gland.

Morphogenesis and cytodifferentiation of the salivary glands are dependent on epithelio-mesenchymal interactions, which are mediated either by direct intercellular contacts or by the expression of signaling molecules. One of these signaling molecules, fibroblast growth factor (FGF), is known to play a crucial role in embryonic cell proliferation, cell differentiation and cell migration. FGF-2 has been identified as a factor facilitating neoplastic progression in salivary glands in humans. The aim of this study was to elucidate the spatial and temporal expression of fibroblast growth factor-2 (FGF-2) in the developing rat submandibular gland. Submandibular glands were removed from foetal rats on days E14.5, 15.5, 16.5, 18.5 and 19.5. Immunolocalization utilizing an antibody to FGF-2 was performed on sections of the submandibular gland at all the derived stages. Diffuse and faint immunolocalization of FGF-2 was seen in the epithelium and mesenchyme of the submandibular gland on days E14.5, E15.5 and E16.5. Intense immunoreactivity for FGF-2 was observed in epithelial components of the gland i.e. in the differentiating acini and ducts, on day E18.5, while on day E19.5, the signal was again less intense. These observations suggest that FGF-2 may play a specific role in cytodifferentiation of the submandibular gland at a particular stage of development.

Animals↗

Parasympathetic schwannoma of the submandibular gland.

Schwannomas of the submandibular gland have only been documented sporadically throughout the medical literature. We describe a case of schwannoma of the submandibular gland originating from the submandibular branch of the lingual nerve, which carries the preganglionic parasympathetic nerve fibers. The clinical aspect of this tumor is discussed, followed by a brief literature review.

Autonomic Fibers, Preganglionic↗

Measurement of heat production in dog submandibular gland.

In dog submandibular glands, we measured changes in metabolic heat production during a secretory period which was induced by electrical stimulation of the chorda tympani. When measured with fine thermocouples, the temperature of both the gland itself and venous blood from the gland increased by 0.1-0.7 degrees C at the maximum. The blood flow was about 0.3 g.min-1.g-1 wet weight of gland at a resting period and increased to 1-3 g.min-1.g-1 at the maximum of secretory response. The resting heat production in vitro, measured by a microcalorimeter, was 3.3 mW.g-1 at 27 degrees C and 7.8 mW-g-1 at 37 degrees C. The specific heat of the blood and the salivary gland, measured by a microcalorimeter, were 3.97 and 3.91 J.g-1, degrees C-1, respectively. The change in conductive heat loss, measured by a thermopile under stimulated conditions, ranged from 4 to 6 mW.g-1 at the maximum. Metabolic heat production during secretion in vivo (37 degrees C) was estimated from temperature changes in the glandular tissue and blood, blood flow, specific heat and resting heat production. Values obtained were in the range from 15 to 80 mW.g-1 at the maximum. Heat production increased rapidly within the first 20 sec to reach a maximum and then declined with time, but slow heat production continued. On the basis of the present results together with those from former studies on ionic transport in the salivary gland, we discussed the relation of heat production to transport of substances during secretory processes.

Animals↗

Molecular cloning of developmentally regulated neonatal rat submandibular gland proteins.

At birth, the rat submandibular gland (SMG) contains two transient secretory cell types that produce several characteristic salivary proteins. Proteins SMG-A, B1, and B2 (23.5, 26 and 27.5 kDa) are products of the neonatal type III cells, but not the adult acinar cells. Protein C (89 kDa), a major product of the neonatal type I cells, is either absent or present at greatly diminished levels in the secretory cells of the adult gland. The decrease in biosynthesis of these neonatal salivary proteins occurs concomitantly with the increase in levels of characteristic adult SMG products. In order to understand these developmentally regulated changes in SMG salivary protein gene expression, we have initiated the molecular cloning and characterization of neonatal submandibular gland proteins from a 5-d-old rat submandibular gland cDNA library. Clones encoding SMG-A were isolated by homology to the mouse parotid secretory protein (PSP). SMG-A was shown to be derived from a salivary protein multigene family that also includes PSP. Cloning and characterization of additional neonatal rat submandibular gland proteins was initiated by screening the 5-d-old rat submandibular gland cDNA library with first strand cDNA prepared from 1-d-old rat submandibular glands. Clones corresponding to a highly abundant 3 kb transcript present in the neonatal rat SMG, but not in adult submandibular, sublingual, or parotid gland have been identified. The size, abundance, and organ specificity of this transcript suggest that it may encode protein C.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Protection by selenium of lead-acetate-induced alterations on rat submandibular gland function.

Pure submandibular saliva was collected intraorally by micro polyethylene cannulation of anaesthetized rats using pilocarpine as a secretagogue. Twenty-four days treatment with lead acetate 0.05% in drinking water altered salivary function. Except for flow rate that was (P<0.01) increased by lead acetate, the reminder of parameters, concentrations of total protein and calcium and the activity of N-acetyl-beta-D-glucosaminidase (NAG) in submandibular secretions were decreased significantly (P<0.01) by lead acetate. Selenium (2.5 mg l(-1)) in drinking water for 24 days did not induce any significant change in saliva secretory function. Pretreatment by selenium, prevented the lead acetate-induced decrease of NAG activity and concentrations of calcium and protein (P<0.01). The increased flow rate by lead acetate was also affected by selenium pretreatment and reached the level of control. It is concluded that selenium can protect rat submandibular gland function from lead-acetate-induced adverse effects. Properties of selenium as an antioxidant, free radical scavenger and maintenance of cell membrane integrity may be possible mechanisms of its protective effects.

Acetylglucosaminidase↗

Differential expression of proliferative, cytoskeletal, and adhesive proteins during postnatal development of the hamster submandibular gland.

Although the submandibular gland (SMG) plays important exocrine and endocrine roles, little is known about the molecular details underlying its development. Previously, we reported that in the postnatally developing hamster SMG, GPT, the protein product of the first N-glycosylation gene, ALG7, was an in vivo marker for salivary cell proliferation. Here we investigated the proliferative, cytoskeletal, and adhesive changes during SMG postnatal development. The cellular localization and abundance of GPT, filamentous actin, and beta1 integrin receptor were examined using confocal microscopy and immunoblotting. In neonatal glands, high GPT levels marked extensive cell proliferation throughout the tissue. The apical regions of immature salivary cells displayed intense actin staining, while most of the beta1 integrin was diffusely distributed throughout the tissue. As development proceeded, discrete regions of the gland expressed attenuated levels of GPT, an increased organization of actin to the cell cortex, and beta1 integrin to the basal lamina. In the adult SMG, differentiated salivary cells displayed low levels of GPT and actin. While the abundance of beta1 integrin remained unchanged throughout development, in the adult, it was found exclusively in regions where cells contact the basal lamina. These data indicate that SMG development entails regionalized cell proliferation and polarization, and that these processes are temporally and spatially coordinated with the establishment of stable cell-substratum interactions.

Actins↗

Partial dissociation between salivary secretion and active potassium transport in the perfused cat submandibular gland.

Isolated cat submandibular glands were perfused with Locke solutions in a thermostated chamber. Passive loss of potassium and uptake of sodium was achieved either by increasing the permeability of the cell membranes by acetylcholine (ACh) or by inhibiting the sodium-potassium pump reversibly by cooling or by removal of extracellular potassium. Irrespective of the way by which the cells were potassium depleted and sodium loaded, re-establishment of normal conditions was sufficient to cause an active net uptake of potassium (probably coupled to net extrusion of sodium). However, while ACh-induced changes in intracellular concentrations of monovalent cations were accompanied by salivary secretion, virtually no secretion was observed when normal conditions were re-established after concentration changes caused by inhibiting the sodium-potassium pump. It is concluded that while the transport mechanisms responsible for the maintenaance of the intracellular concentrations of monovalent cations undoubtedly is a (Na+-K+)-activated ATPase, the transport mechanism responsible for the formation of the primary saliva is probably of a different type, since it apparently is not directly activated by the intracellular sodium concentration.

Acetylcholine↗

Characteristics and localization of rat submandibular gland proteoglycans.

The submandibular gland proteoglycans were investigated biochemically and immunohistochemically in male Sprague-Dawley rats. Proteoglycans were extracted with 4 M guanidine-HCl, followed by ultracentrifugation in a CsCl density gradient, and fractionated by ion-exchange chromatography and gel filtration. The molecular weight of PGs was estimated by SDS-PAGE and immunoblot analysis with monoclonal antibodies (HepSS-1 or 6-B-6). The glycosaminoglycan side-chains in the proteoglycan fractions were identified by electrophoresis on cellulose acetate membrane. Three proteoglycan fractions were obtained. One was a heparan sulphate proteoglycan that migrated as a diffuse band of about 210 kDa. The other two fractions contained at least two dermatan sulphate proteoglycans of 70-85 kDa and 40-50 kDa. Digestion of these two proteoglycans with chondroitinase ABC, but not heparitinase, produced two bands of 50 and 21 kDa, which were core proteins. The smaller dermatan sulphate proteoglycan may be a portion of the other, as the core protein of both bound to 6-B-6 antibody, and sugar chains of both were the same (20-30 kDa). Heparan sulphates recognized by antibody HepSS-1 were observed widely in the basement membrane, fibrous connective tissue, and striated and excretory ductal cells, while dermatan sulphate proteoglycans recognized by antibody 6-B-6 were located in the connective tissue surrounding striated and excretory ducts.

Animals↗

[The development and collagen ingredients analysis of submandibular gland acellular matrix].

PURPOSE: To develop submandibular gland acellular matrix and observe its structure and analyze its histological ingredients. METHODS: The fresh submandibular glands of SD mice were cell-extracted by chemical detergent and histological ingredients were analyzed by immunohistochemistry. RESULTS: Submandibular gland cells disappeared, matrix ingredients appeared network structure under microscopy. I, II and III type collagen proteins of submandibular gland before and after cell-extracted were positive under immunohistochemistry. CONCLUSIONS: The main ingredients of submandibular gland acellular matrix were I, II and III type collagen proteins.

Acellular Dermis↗

Anterior facial vein and submandibular gland together: predicting the histology of submandibular masses with CT or MR imaging.

PURPOSE: To test the hypothesis that the relationship of the anterior facial vein to the submandibular salivary gland and a mass in the submandibular fossa could help identify the origin of the mass at computed tomography (CT) or magnetic resonance (MR) imaging. MATERIALS AND METHODS: Thirteen patients with 14 palpable submandibular masses, surgical and histologic confirmation, and contrast material-enhanced CT images (12 patients) or MR images (one patient) that showed the anterior facial vein were identified with review of files from 1985 to 1997. Six patients had submandibular gland disease: three with primary neoplasms, two with metastatic tumor invading the gland, and one with chronic sialoadenitis. Eight patients had masses arising outside the gland (seven with lymphadenopathy, one with a plexiform neurofibroma). RESULTS: The anterior facial vein did not separate primary tumors, tumors invading the gland, or lobulations of the enlarged gland from the body of the gland. The vein was identified between enlarged lymph nodes and the gland. The vein did not separate the gland from the neurofibroma, but this tumor was medial to the gland; the vein runs lateral to the gland. CONCLUSION: The anterior facial vein is a useful landmark in determining the origin of a submandibular mass. Primary disease of the gland is never separated from the gland by the vein. The vein does separate lymphadenopathy from the gland and, theoretically, separates the gland from soft-tissue tumors lateral to the gland.

Adult↗