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Expression of S-100 protein and glial fibrillary acidic protein in cultured submandibular gland epithelial cells and salivary gland tissues. Histogenetic implication for salivary gland tumors.

S-100 protein and glial fibrillary acidic protein (GFAP) were studied in human salivary gland tissues and human cultured submandibular gland epithelial cells. Immunohistochemically, ductal cells in normal salivary gland tissues were positive for S-100 protein and GFAP, but myoepithelial cells were uniformly negative. Immunocytochemically, cultured submandibular gland ductal cells were positive for S-100 protein and GFAP. By immunoblotting analysis of the cultured cell lysates, a 6.5-kd S-100 protein was detected. This band corresponded to S-100 protein purified from bovine brain. The cultured submandibular gland cells expressed 49- and 54-kd GFAP polypeptides. These results have important implications for the histogenesis of salivary gland tumors.

Animals↗

[Evaluation of normal submandibular gland function by sialo-scintigraphy].

OBJECTIVE: To study the normal glandular function of the submandibular gland as a background for evaluation of changes in submandibular gland diseases. METHODS: The backgrounds of both submandibular area and temporal area were analyzed comparatively with Emission Computerized Tomography in eleven pairs of normal submandibular gland. RESULTS: About 2.18 times of the temporal background equals to submandibular area background; the Concentrate Index of normal submandibular gland was 1.42 +/- 0.89; the Secretory Index was (109.4 +/- 39.8)%, the Secretory Index Ratio and the Concentrate Index Ratio were (77.2 +/- 17.2)% and 71.0 +/- 15.2% respectively; and the Function Index was (89.9 +/- 7.4)%. CONCLUSION: The use of submandibular area background and functional index to represent submandibular gland function is more accurate and more sensitive. Normal functional index can provide the basis for researching submandibular gland disease.

Humans↗

Histochemical localization of salivary glycoproteins in the submandibular gland of aging rats.

It is known that submandibular glands produce serous saliva in the serous demilune cells and mucous saliva in the mucous acinar cells which is a viscous, rich in glycoproteins substance. The aim of this study was the comparative histochemical investigation of acid and neutral salivary glycoproteins in the acinar cells of the submandibular gland in adult and aging rats. Three groups of female Wistar rats were studied: a) young adult rats, 3 months old, b) aged rats 25 months old, c) aged rats 30 months old. Each group included 5 animals. The animals were sacrificed with ether in toxic dose. The submandibular glands were dissected and placed in 10% formaldehyde solution. After fixation they were embedded in paraffin. The paraffin sections were stained with various techniques. We used the: a) Alcian-Blue PH 2,5-Neutral Red b) Periodic-acid/Schiff/Diastase c) Alcian-Blue PH2,5 and Periodic-acid/Schiff/Diastase. We observed that the acinar cells of the aged submandibular glands were filled with acid glycoproteins, while the neutral glycoproteins were localized only in the group of the adult rats. Our results confirm the theory, that lithiasis and chronic inflammations of the submandibular gland, which often happen after the 4th decade of the life, are due to alterations of the mucosubstance composition of the acinar cells.

Aging↗

[The quantitative and qualitative analysis fro submandibular gland of human being.].

30 cases of submandibular gland tissue were determined quantitatively in this article.It is noticed that there was no great change during and after the birth .But at the adolesence stage,the data began to change was steady in adult state.At pressenium,the change speed of mean was faster.Observation under microscope:the submandibular gland in 7-8 month old embryo was developed basically and similar to newborn.It had good blood supply and secrete function.Adipose tissue,which is important indication of changed with age in saliva gland,did not exit in submandibular gland of human being.In addition.it is normal that there were a few lymphatic cells and plasmocytes with secrete SIgA in the gland and is relating with protective principle of normal environment.

English Abstract↗

Molecular characterization of glutamic acid/glutamine-rich secretory proteins from rat submandibular glands.

A family of abundant rat submandibular gland secretory proteins has been identified in glandular extracts and characterized. By amino acid analysis these proteins contain approximately 35% glutamic acid and glutamine plus 14% proline. They have therefore been named "Glx-rich proteins" (GRP). Plasmids containing cDNAs for a GRP have been isolated from a cDNA library prepared from rat submandibular gland poly(A)+RNA. The nucleotide sequence of these cDNAs have been determined. Approximately half of the protein coding sequence is composed of a 23-residue tandem repeat which is repeated five times. The first four repeats are highly conserved at both the nucleotide and amino acid level and consist of the prototype sequence: Asn-Gln-Glu-Pro-Pro-Ala-Thr-Ser-Gly-Ser-Glu-Glu-Glu-Gln-Gln-Gln-Gln-Glu- Pro-Thr-Gln-Ala-Glu. The expression of GRP appears to be specific to the submandibular gland. In vitro assays demonstrate that the GRP have a marked affinity for hydroxyapatite. This suggests that GRP may play a role in the formation of the protective acquired pellicle at the saliva-tooth interface.

Amino Acid Sequence↗

Age-related changes in EGF and protease in submandibular glands of C57BL/6J mice.

The submandibular glands of male C57BL/6J mice were studied cytologically and chemically at the following ages (months): 1-1.5, 6-8, 12-13, 28-32. The relative proportion of granular convoluted tubules (GCT), as well as the size and content of secretion granules of GCT cells, progressively increased throughout the first year of life. Correspondingly, the concentration within the glands of two GCT cell products, epidermal growth factor (EGF) and protease, also steadily increased. In senescent glands, GCTs formed relatively less of the gland parenchyma and were composed of shorter cells with reduced amounts of secretory granules. The concentration of EGF was reduced to 17% of its peak value at one year, while protease activity declined to 50% of its peak value. These morphologic and chemical findings imply a functional impairment in submandibular glands of the mouse with senescence.

Aging↗

Metastasis to the submandibular gland in head and neck carcinomas.

BACKGROUND: The purpose of this retrospective chart review was to determine whether and how the submandibular gland is involved in metastases of squamous cell carcinoma of the head and neck. METHODS: We reviewed the records of all patients for whom pathology specimens were available after neck dissection for primary head and neck cancers at two institutions. RESULTS: One hundred sixty-nine patients were included in the study, 27 underwent bilateral neck dissections, and 196 submandibular glands were resected and sent for pathology. One hundred forty-four glands had normal histologic findings. Normal or benign histologic changes were present in 187 glands. Three submandibular glands showed invasion from a locally involved lymph node, and six had direct extension from a primary lesion. The primary lesions were all ipsilateral to the involved gland and originated from cancers of the floor of the mouth, alveolar ridge, and tongue. No submandibular glands showed pathologic evidence of metastases. CONCLUSIONS: Because the submandibular gland has no intraparenchymal lymph nodes, its involvement in upper aerodigestive tract carcinomas must be through extension from a locally involved lymph node or the primary tumor. Previous work has demonstrated that the submandibular gland can undergo transplantation out of the neck with subsequent reimplantation, as a possible means of protection from the effects of radiation. We demonstrated the submandibular gland to be involved only in cases of ipsilateral oral cavity tumors or metastasis to ipsilateral level I lymph nodes. We conclude that it is oncologically sound to consider transplantation and replantation of the contralateral submandibular gland for patients with head and neck squamous cell carcinoma when level I lymph nodes are unlikely to be involved.

Adult↗

Scanning electron microscopy of the human submandibular gland.

We examined human submandibular gland parenchyma by scanning electron microscopy after removal of connective tissue components by HCl hydrolysis. Stellate-shaped myoepithelial cells and basal infoldings were clearly seen, indicating active function of the gland.

Humans↗

The effects of 5-bromodeoxyuridine and isoproterenol on the postnatal differentiation of rat submandibular gland.

The effects of 5-bromodeoxyuridine (BrdU) on the postnatal differentiation of rat submandibular gland and on the isoproterenol-induced changes of differentiation were studied. The rats were injected with BrdU for three consecutive days, beginning at two days of age. The total dose of BrdU was 0.9 mg/g body weight. BrdU caused a severe retardation of growth up to 15 days of age. A rapid growth of the animals between 15 and 22 days indicated a recovery from the effect of BrdU. The growth of the submandibular gland was retarded similarly with a corresponding decrease in DNA, RNA and protein content. Incorporation of tritiated thymidine into the submandibular gland was not altered in the BrdU-treated animals at one and three days after the last injection of the analog. At days 15 and 22 the rate of thymidine incorporation was greater in the submandibular gland of BrdU-treated rats as compared to littermate controls. Isoproterenol stimulated thymidine incorporation into the submandibular glands of two-week-old rats. This stimulation was not observed in rats which received BrdU at age 7-9 days, prior to the administration of isoproterenol. Election microscopic observations, including a quantitative analysis of the frequency distribution of the various cell types in the terminal tubules and developing acini, indicated a retardation of acinar cell differentiation in the glands of BrdU-treated rats. In addition, there was an increase in the number and size of the secretory granules in the terminal tubule cells. BrdU treatment, however, caused no obvious pathologic alterations in the submandibular gland. Administration of isoproterenol for five days, beginning at five days of age, caused an apparent acceleration of the differentiation of acinar cells. In the glands of isoproterenol-treated rats the acinar cells were enlarged and were filled with homogeneous secretory granules. Pretreatment with BrdU partially inhibited the effects of isoproterenol on differentiation and hypertrophy of the submandibular gland. With the given dose of BrdU, approximately 5% of thymine was replaced by bromouracil in the DNA of the submandibular gland. Such a replacement would be consistent with a direct effect of BrdU on the cytodifferentiation in the submandibular gland. However, because of the severe retardation of growth of the BrdU-treated rats, indirect effects can not be excluded.

Animals↗

Cytochrome oxidase activity and confocal laser scanning microscopic analysis of the hamster submandibular gland using microwave irradiated fixation.

Submandibular glands of the hamster were irradiated in 2% paraformaldehyde (pFA)-0.5% pure glutaraldehyde (PGA) with a microwave (MW) processor at temperatures of 10 degrees and 37 degrees C. Electron microscopy showed that cytochrome oxidase activity was taking place in the mitochondrial intermembrane-intracristal space of the granular duct cell when the temperature of the MW-irradiated fixatives was at 10 degrees C. However, a decrease of this activity was observed when we took care to keep the temperature of the MW-irradiated fixatives at 37 degrees C. The distinct reduction of cytochrome oxidase activity allowed by MW irradiation seems to be due the thermal affects of fixatives. Of course, the possibility cannot be excluded that MW irradiation caused other undetectable membrane damage. Then, we used confocal laser scanning microscopy for the preservation check of the mitochondrial membrane for cytochemistry with MW-irradiated fixation. The fluorescence of rhodamine 123 was observed in the inner spaces of the mitochondria at temperatures of 10 degrees and 37 degrees C. When the same tissues were fixed with 2% pFA using an MW processor as the sole fixative at 10 degrees C, no mitochondrial fluorescence was observed. Cytochrome oxidase activity, by contrast, could be seen in the mitochondrial intermembrane-intracristal spaces in the same condition. Formaldehyde is not the best aldehyde for the purpose of ultrastructural preservation. On the other hand, light and electron microscopy showed that the endogenous peroxidase activity was localized in the nuclear envelope, endoplasmic reticulum, secretory granules, and Golgi apparatus of the hamster submandibular gland using 2% pFA-0.5% PGA fixative with and without MW irradiations at temperatures of 10 degrees and 37 degrees C. Some of the same cells were fixed with only 2% pFA under MW irradiation at 10 degrees C; however, marked diffuseness of the peroxidase activity was observed. Therefore, these results indicated that cytochrome oxidase activity was sensitive to heat with MW-irradiated fixation. Peroxidase activity was very resistant to heat with MW-irradiated fixation but not with pFA solo fixation, therefore, PGA had to be used.

Animals↗

[Effects of mastication and submandibular gland ectomy on the growth ability of isoproterenol-stimulated parotid gland and other tissues in male mice].

In a previous article we reported that mastication played an important role in the development of submandibular glands in male mice. Submandibular glands contain epidermal growth factor (EGF) which stimulates the proliferation of various cells in developing animals. In this study, the effects of the hypotrophy of submandibular glands caused by reduction of mastication and the removal of the glands on the growth ability of isoproterenol (IPR)-stimulated parotid glands and other tissues were investigated. The animals in the experiment were male mice and they divided into three groups, a control group fed a solid diet, a group fed a paste diet and a group with removed submandibular glands fed a solid diet. In comparison with the group fed a solid diet, in the group fed a paste diet a small decrease was found, and in the group with the ectomized submandibular gland a significant decrease in the rise of ornithine decarboxylase (ODC) activity, S-adenosylmethionine decarboxylase (SAMDC) activity and DNA synthesis of parotid glands caused by IPR stimulation were found. The DNA synthesis of the heart tissue of mice with ectomized submandibular glands was lower than that of the control group, but in liver, lung, stomach and testis tissue no decrease of DNA synthesis was found. These results suggest that mastication and the submandibular glands have an effect of the growth of the tissues in male mice.

Animals↗

Analysis of 185 submandibular gland excisions.

A review of 185 submandibular gland excisions over a ten year period is presented. The symptoms, physical findings, diagnosis on pathological examination and prognosis have been noted in each case to determine the incidence of neoplastic versus non-neoplastic disease. In our series non neoplastic disease of the submandibular gland was found in 141 patients (76%) with a large predominance of inflammatory lesion, while only 26 patients (14%) had a neoplastic lesion (6 benign lesions and 20 malignant tumors). There were also 18 (10%) patients surgically treated with gland excision for a glandular metastatic involvement from adjacent nodes. The significance of these findings is discussed.

Adolescent↗

Androgen receptor in rat Harderian and submandibular glands.

Androgens regulate the development and sexual dimorphism of rodent Harderian and submandibular glands. This effect is believed to be mediated by the androgen receptor. Immunohistochemistry and immunoblotting were carried out to study the receptor in normal, castrated and dihydrotestosterone-supplemented rat Harderian and submandibular glands. Immunohistochemically, the most intense nuclear staining was observed in the acinar cells of the submandibular glands, followed by intercalated duct cells. The granular convoluted tubules showed weak immunostaining and the striated ducts were negative. In the Harderian gland, nuclear staining was seen in both type I and II secretory cells. Castration and treatment had no effect on the expression of the androgen receptor protein in either gland. A 110 K androgen receptor signal was detected by immunoblotting in the Harderian gland but not in the submandibular gland. An experiment was designed to explore the possible effect of proteinases on the receptor protein in the homogenate of submandibular gland. Our results demonstrate the cell-specific location of the receptor in Harderian and submandibular glands, and show that the expression of the receptor protein is androgen-independent.

Animals↗

The postnatal development of the sexually dimorphic duct system and of amylase activity in the submandibular glands of mice.

The submandibular glands of developing and mature Strong A mice were studied by light and electron microscopy. The glands of both sexes show the same cell types during development, but during maturation the glands display a degree of sex-dimorphism. Striated ducts, which differentiate from the larger intralobular ducts present in the neonatal gland, first appear by 5 days of age and reach their mature condition by 20 days of age. Granular convoluted tubule cells, which differentiate from striated duct cells, are first seen at 15 days of age in both sexes. Subsequently, they show a more rapid development in males than in females, and are dimorphically represented by 20 days of age. Intercalated ducts in the neonatal gland contain nongranular and granular cells. With maturation the number of granular cells decreases, apparently due to their conversion into the nongranular type, with their eventual disappearance from the glands of adult males. Their retention in adult females further defines the sexual dimorphism shown by these glands. Amylase activity in gland homogenates is first detectable at 20 days of age in both sexes. During development the male glands show a rapid rise in levels of amylase activity, whereas female glands show a more gradual rise. In mature animals, male glands have higher levels of amylase activity than female glands. The developmental and adult status of amylase activity parallels that of the granular convoluted tubules.

Age Factors↗

[On the pathogenesis of the Küttner tumor of the submandibular gland -- Analysis of 349 cases with chronic sialadenitis of the submandibular (author's transl)].

In view of the etiology and pathogenesis of the so-called Kütter tumor (chronic sialadenitis of the submandibular gland) gland resections of 349 patients (salivary gland register at the Institute of Pathology, University of Hamburg; period 165--1974) were analyzed pathohistologically. In 143 cases (41%) a sialolithiasis of the submandibular gland occurred simultaneously. Regarding the degree of the inflammation 4 stages were distinguished (stage 1 = focal sialadenitis; stage 2= diffuse lymphocytic sialadenitis with salivary gland fibrosis; stage 3 = chronic sclerosing sialadenitis with salivary gland sclerosis; stage 4= chronic progressive sialadenitis with salivary gland cirrhosis). Twenty-five per cent of the cases were classified in stage 1, 19% in stage 2, 38% in stage 3, and 18% in stage 4. A predominance of the male sex (70%) was observed especially in stage 4. The initial stage is characterized by a periductally lymphocytic infiltration, ectasias of the ducts, and alteration of the secret in the duct lumens (spheroliths, microliths). In stages 2--3 an increase of the inflammatory infiltration with lymph follicles, considerable alterations of the ducts (metaplasias, dysplasias, regenerates of the ducts), and a parenchymal reduction were found. This process is combined with an increase of the interstitial connective tissue and a cicatrication of the salivary gland parenchyma. In the final stage, 4, a cirrhotic gland transformation with progressive loss of the parenchyma and considerable duct destruction appeared. From the pathogenetic course of the inflammation and the comparison with other forms of sialadenitis, the conclusion is drawn that two etiologic factors are important in the Küttner tumor: an initial disturbance of secretion with an obstructive electrolyte sialadenitis and an immune reaction of the salivary duct system with the final phase of an obstructive, progressive immunosialadenitis.

Adolescent↗

Cut-down sialography of the submandibular gland.

Sialography of the submandibular gland which is often deferred because of inability to isolate, dilate, and cannulate Wharton's duct, can be safely accomplished with minimal morbidity with use of a modification of the surgical procedure to remove a salivary ductal calculus. It can be accomplished as an office procedure in ambulatory patients.

Humans↗