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PubMed1980

A case report of basal cell adenoma showing elastic fiber (elastin-basement membrane complex) formation of the submandibular gland.

A biopsy case of basal cell adenoma of the submandibular gland was reported in a 15-year-old boy. The tumor was pigeon's egg-sized, spherical in shape and encapsulated by fibrous tissue, and its cut-surface was grayish white. Histologic feature of this neoplasm was a trabecular or tubular monomorphic adenoma with well-developed elastic fibers (elastin-basement membrane complex) in the interstitial tissue. Electron microscopy disclosed 4 kinds of tumor cells, that is, secreting cells, squamous cell-like cells with tonofibrils and tonofilaments, clear cells with a few filaments, and myoepithelial cells. The interstitium contained elastin, collagen fibrils and basement membrane-like substance. Possible production of elastic fibers by the myoepithelial cells of this adenoma was discussed.

Adenoma↗

PubMedDate not supplied

Isolated submandibular gland metastasis from an occult papillary thyroid cancer.

A case of an isolated submandibular gland metastasis from a clinically occult papillary thyroid carcinoma is described in a 46-year old lady. Initial surgery was done based on the fine needle aspiration cytology (FNAC) report of adenocarcinoma of the submandibular gland. Histopathologic examination of the specimen suggested a metastatic papillary carcinoma. Occult papillary carcinoma in the thyroid was found by multiple blind FNACs. Subsequently to near-total thyroidectomy, no other site of metastasis was found on radio-iodine scanning.

Carcinoma, Papillary↗

PubMed1993

Distribution of alpha 6 integrin subunit in developing mouse submandibular gland.

We examined the development of mouse submandibular gland by light and electron microscopy and determined the distribution of the alpha 6 integrin subunit and laminin in this process by immunofluorescence and immunoelectron microscopy. At Days 13.5 and 14 of gestation alpha 6 was localized over the entire cell surface of undifferentiated epithelial cells of the terminal cluster. On Day 15 the expression of alpha 6 could no longer be detected over central cells in the proximal portion of branched terminal cluster, whereas peripheral cells were stained over the entire surface. On Day 17 of gestation to day of birth, alpha 6 expression was restricted to the basolateral surface of the differentiated acinotubular structure. Its expression on acinar cells was uniformly distributed throughout the basolateral membrane, but on duct cells stronger staining towards the basal surface was noted. Similar expression was observed in adult acinar and duct cells. Expression of the alpha 6-subunit at the cell-cell contact in an early stage and its expression at the basolateral surface in an advanced stage indicate that integrin containing alpha 6 plays a significant role in cell-cell and cell-substrate interaction. Stage and cell type-specific change of integrin expression may be significant for submandibular development.

Animals↗

PubMed1983

Cell-free translation of proline-rich protein mRNAS from human submandibular gland.

RNA was isolated from a human submandibular gland and separated into poly A-enriched and poly A-deficient fractions by chromatography on oligo (dT) cellulose. Both of these RNA fractions stimulated methionine incorporation into polypeptides in a reticulocyte lysate translation system. Two in vitro translation products templated by poly A-enriched mRNA were isolated by immunoprecipitation with immune serum directed against human salivary anionic proline-rich protein I. These polypeptides were shown to be precursors of proline-rich proteins on the basis of Mr, affinity for the antiserum, and preferential incorporation of proline. This study is the first to demonstrate cell-free translation of the mRNAs for human proline-rich salivary protein precursors.

Aged↗

PubMed1994

The effect of irradiation on blood flow through rabbit submandibular glands.

Microspheres labelled with radioactive isotopes were used to study blood flow through irradiated rabbit submandibular glands before and after injection of pilocarpine. The blood flow through the submandibular glands was measured by the microsphere technique with satisfactory accuracy. A single radiation dose of 13.1 Gy at 3 months of age reduced blood flow through the whole gland significantly 4 months later, and even more at 10 months after irradiation. However, the relative blood flow (per gram of gland tissue) was almost unaffected at both 4 and 10 months post-irradiation with 13.1 Gy because of the simultaneous reduction of gland parenchyma.

Animals↗

PubMed1983

Cholinergic stimulation of ouabain-sensitive respiration in rat submandibular gland.

Oxygen consumption of slices of rat submandibular gland was monitored with an oxygen electrode method. Carbachol stimulated an immediate increase in tissue respiration that was inhibitable by ouabain. The stimulation required the presence of calcium in the incubation medium and was blocked by atropine. The calcium ionophore A23187 also stimulated ouabain-sensitive oxygen consumption in the tissue slices. The results show that the mechanism using the extra energy during cholinergic stimulation is the sodium pump. Amiloride at a 1, 10, or 100 microM concentration had no effect on stimulation of ouabain-sensitive respiration by carbachol. Since amiloride, which is known to block the sodium reabsorption process in the ductal segment, has no effect on the stimulation, the increased sodium pump activity is probably located in the acinar region and is associated with the primary fluid secretion process.

Amiloride↗

PubMed1982

Analysis of reflex responses in preganglionic parasympathetic fibres innervating submandibular glands of rabbits.

1. The volume of submandibular salivary secretion and electrical activities in preganglionic parasympathetic fibres innervating the submandibular gland were recorded in rabbits, anaesthetized with chloralose-urethane, to evaluate the neural control mechanisms subserving reflex salivary secretion. 2. Single, paired or repetitive electrical shocks were applied to the various parts of the oral region in sympathetically decentralized animals. A copious salivary secretion was induced when the repetitive electrical stimulation was applied to anterior ipsilateral parts of the oral region, especially the upper lip. The optimum frequency of stimulation was 10--20 Hz. 3. About 90% of the preganglionic parasympathetic fibres responded to single electrical shock applied to a respective confined area of the oral region with a mean latency of 10.8 msec. The remainder responded to wider areas of the oral region with a mean latency of 31.5 msec. 4. Preganglionic fibres were classified into three types (E-type, N-type and I-type) in accordance with the mode of impulse discharges. Spontaneous discharges of E-type fibres (41%) were increased, while those of N-type fibres (36%) were unchanged and those of I-type fibres (23%) were decreased by repetitive stimulation at over 10 Hz. Most dominant responses in E-type fibres were induced by electrical shocks with a frequency of 10--20 Hz. 5. When paired shocks with varying intershock intervals were applied, excitability of E-type fibres was enhanced for about 20 msec, and then inhibited for about 100 msec, while that of N-type was inhibited for 150--200 msec, and I-type was inhibited for 500--700 msec after onset of the first shock. 6. The volume of reflex submandibular salivation evoked by varying frequencies of electrical shocks applied to the oral region correlated statistically significantly with the magnitude of responses in E-type fibres. This result strongly suggests that E-type fibres are secretory fibres. The functional significance of N-type and I-type fibres is discussed.

Action Potentials↗

PubMed1998

High-frequency color Doppler sonography of the submandibular gland: relationship between salivary secretion and blood flow.

OBJECTIVE: The purpose of this study was to evaluate the changes of blood flow of the submandibular gland in comparison with salivary secretion after gustatory stimulation through use of color Doppler sonography. STUDY DESIGN: High-frequency color Doppler sonography was performed on 30 healthy volunteers, aged 22 to 31 years. The prestimulation and poststimulation arterial blood flows were evaluated with color Doppler sonography and spectral analysis. RESULTS: The means of prestimulation maximum and minimum velocities and pulsatility index of the submandibular gland were 6.35 +/- 2.57 cm/sec, 1.79 +/- 0.93 cm/sec, and 1.53 +/- 0.42, respectively. After the stimulation, the color signals and velocities increased and the pulsatility index decreased. There was a close correlation between the increase in minimum velocity and that of salivary secretion. CONCLUSION: Color Doppler sonography is useful in analyzing changes in the blood flow of the submandibular gland caused by gustatory stimulation.

Adult↗

PubMed1993

Effect of thyroid hormone on epidermal growth factor gene expression in mouse submandibular gland.

Epidermal growth factor (EGF) in mouse submandibular gland (SMG) is synthesized in the granular convoluted tubular (GCT) cells. The synthesis of EGF in SMG has been shown to be increased by thyroid hormone. This increase was attributed to the increase in EGF mRNA. Not known is how thyroid hormone increases the mRNA level. In the present study the effect of thyroid hormone administration on EGF gene expression in SMG was studied in hypothyroid mice. Hypothyroidism was induced by treating the mice with propylthiouracil. The amount of SMG EGF mRNA was markedly decreased in hypothyroid mice. Administration of T3 increased the mRNA in a dose-dependent manner. The increase in EGF mRNA by T3 was evident as early as 6 h after T3 administration. A nuclear run-off assay indicated that the induction of EGF gene expression by T3 is at a transcriptional level. Bromodeoxyuridine incorporation into GCT cells was not affected by T3 administration, suggesting that T3 does not cause the proliferation of these cells. In situ hybridization revealed that T3 increases EGF mRNA in GCT cells at a single cell level. These results suggest that thyroid hormone increases EGF gene transcription without affecting cellular proliferation.

Animals↗

PubMed2000

Immunoglobulin A secretion into saliva during dual sympathetic and parasympathetic nerve stimulation of rat submandibular glands.

Salivary secretion of proteins from rat submandibular glands was studied using graded stimulation of the parasympathetic nerve in isolation, and then at a fixed rate in combination with graded sympathetic nerve stimulation. Increasing the frequency of parasympathetic nerve stimulation per se caused a gradual increase in the secretion of peroxidase (from acini) but only small increases in proteinase (from ductal cells) and IgA outputs. Dual stimulations, with an increasing frequency of sympathetic nerve stimulation on a background of low frequency parasympathetic nerve stimulation, showed that maximal acinar secretion of peroxidase required only a low frequency of additional sympathetic stimulation, whereas ductal secretion of kallikrein was greatest with the highest frequency of additional sympathetic stimulation (20 Hz in bursts). IgA secretion also required high frequency additional sympathetic stimulation in bursts for greatest output. Although a synergism occurred with parasympathetic plus sympathetic nerve stimulation for the secretion of both peroxidase and kallikrein it was not evident for the secretion of IgA. This presumably reflects a difference for exocytosis of proteins stored in granules (e.g. peroxidase and kallikrein) compared to those proteins continuously transported across the plasma membrane in vesicles by transcytosis. This work confirms that vesicular movement of secretory IgA can be increased by both parasympathetic and sympathetic nerve stimulation, but the frequency parameters differ for each nerve.

Animals↗

PubMed1986

Sex difference in the cytosolic and nuclear distribution of androgen receptor in mouse submandibular gland.

Cytosol and nuclear androgen receptors in submandibular glands of male and female mice were measured by an exchange assay at 0 degree C. The binding of [3H]methyltrienolone to cytosol receptors in females was mostly saturated within a short period of incubation (3 h), whereas the saturation was much slower in males; suggesting that almost all of the cytosol receptors were unoccupied in females and the receptors were partially occupied in males. Nuclear receptors were extracted with pyridoxal 5'-phosphate (5 mmol/l) from nuclear fractions with 93-95% efficiency. The exchange of the bound steroids occurred by 24-48 h at 0 degree C, suggesting that most of the nuclear androgen receptor was occupied. The binding was low at higher temperatures, probably due to inactivation of the receptor. Scatchard analysis showed that the apparent dissociation constants of cytosol and nuclear receptors were similar (0.8 and 0.9 nmol/l respectively) in both sexes. On the other hand, the number of androgen-binding sites in the nucleus was much higher in males than in females (1052 fmol/mg DNA and 32 fmol/mg DNA respectively), while the number in the cytosol was higher in females than in males (512 fmol/mg DNA and 368 fmol/mg DNA respectively). These observations show that androgen receptors exist mainly (74%) in the nuclei of males, while they exist mostly (94%) in the cytosol of females.

Animals↗

PubMed2006

Histological and immunohistochemical changes in the submandibular gland in klotho-deficient mice.

The submandibular gland (SMG) has been regarded as an age-stable organ in spite of reports on its structural changes with aging. Although the klotho gene is involved in aging, little information is available regarding its effects on morphological changes of SMGs. The present study examined the histological and immunohistochemical features of SMGs in klotho-deficient mice--which are well-established aging models--by immunohistochemical and histochemical techniques. Five kinds of cellular markers--against NGF, EGF, Mnand Cu/Zn-SOD, and RITC-conjugated phalloidin--were used for the identification of cell types. In klotho-deficient mice, the SMGs lost their granular ducts and each lobe diminished. The granular duct showed strong immunoreactivities for NGF and EGF in the wild-type mice, but the NGF- and EGF-immunopositive ducts decreased in number remarkably in klotho-deficient mice. Interestingly, instead of a loss of the granular duct, the striated duct located on the distal portion in the homozygous mice came to show NGF- and EGF-immunoreactions. Neither Mn- and Cu/Zn-SOD immunoreactivities in the duct system nor the phalloidin- reaction in the myoepithelial cells differed between the wild-type and klotho-deficient mice. Our findings suggest that the klotho gene inhibited the differentiation of the granular duct from the striated duct due to the repression and/or down-regulation of sexual and growth hormones.

Animals↗

PubMed1998

Cells in the duct system of the rat submandibular gland.

The duct system of the rat submandibular gland (granular convoluted tubule [GCT], striated duct, excretory duct, main excretory duct [MED] and salivary bladder) was studied using scanning and transmission electron microscopy, with special reference to the dark and tuft cells. The MED was subjected to histochemistry for horseradish peroxidase (HRP) uptake. The epithelium of the duct system was composed of a heterogeneous cell population. On scanning electron-microscopic observation, principal, dark, and tuft cells were easily distinguished by their microvilli. Principal cells had small microvilli and microridges on their surface. The principal cells of the striated duct had secretory granules in the apical cytoplasm, but those of the excretory duct, the MED, and the salivary bladder had electron-lucent vesicles. Except for the GCT and salivary bladder, the basal infoldings of the epithelial cells were well developed. The dark cells were characterized by regular microvilli, and many tubules and vesicles confined to the apical cytoplasm. They existed in the striated duct, the excretory duct, the MED, and salivary bladder. The so-called pillar cells in the GCT appeared to be identical to the dark cells. Tuft cells had on their surface long, blunt microvilli with prominent rootlets. Many vesicles were observed in the apical cytoplasm. It was concluded that dark and tuft cells were common in the striated duct, the excretory duct, the MED and salivary bladder. Dark cells were observed also in the GCT. Dark and principal cells of the MED showed HRP uptake but tuft cells did not.

Animals↗

PubMed1986

Concentrations of immunoreactive tonin in submandibular glands and saliva of the rat.

The submandibular gland (SMG) of the rat contains tonin, an enzyme of serine proteases, which specifically cleaves angiotensinogen and angiotensin I to yield angiotensin II directly. Using a specific RIA for rat tonin, the present study was performed to examine the concentrations of immunoreactive (IR) tonin in SMG of normal Wistar male rats with various ages, those in SMG and saliva of normal adult males and females, and also its SMG levels of castrated males and testosterone-treated females. The concentrations of IR-tonin in SMG of immature 4 week old male rats were very low but rose exponentially with increasing age to reach adult levels (3-6 micrograms/mg wet tissue) in male rats after 6 week old or more. SMG of the adult male rat contained 10-fold more IR-tonin than that of the female rat and male saliva contained 5-fold more IR-tonin than that of females. The concentrations of SMG IR-tonin in the castrated males fell to about one-tenth the levels of normal males, whereas SMG IR-tonin levels in the testosterone-treated females increased about ten times more than those of normal females. These data confirm the sexual dimorphism of rat SMG with respect to the concentrations of tonin and indicate that androgens play an important role in regulating the synthesis and/or storage of tonin in rat SMG. It is also suggested that tonin is secreted into saliva in concentrations reflecting its SMG levels. However, biological significance of tonin in SMG and saliva remains obscure.

Age Factors↗

PubMed1998

Laminin-1 and laminin-2 G-domain synthetic peptides bind syndecan-1 and are involved in acinar formation of a human submandibular gland cell line.

The culture of human submandibular gland (HSG) cells on laminin-1 induces acinar differentiation. We identified a site on laminin involved in acinar differentiation using synthetic peptides derived from the C-terminal G-domain of the laminin alpha1 and alpha2 chains. The alpha1 chain peptide AG73 (RKRLQVQLSIRT) decreases the size of acini formed on laminin-1. Cells cultured with either AG73 or the homologous alpha2 chain peptide MG73 (KNRLTIELEVRT) form structures that appear acinar-like, but the cell nuclei are not polarized to the basal surface and no lumen formation occurs, indicating that additional sites on laminin are required for complete differentiation. The G-domain of laminin-1 contains both integrin and heparin binding sites, and anti-beta1-integrin antibodies disrupt acinar formation. Cell adhesion to the peptides and to E3, an elastase digest fragment of laminin-1 containing AG73, is specific, since other laminin peptides or EDTA do not compete the binding. Heparin and heparan sulfate decrease cell adhesion to AG73 and MG73 but anti-beta1-integrin antibodies have no effect. Treating the cell surface with heparitinase inhibits adhesion to both AG73 and MG73. We isolated cell surface ligands using both peptide affinity chromatography and laminin-1 affinity chromatography. Treating the material bound to the affinity columns with heparitinase and chondroitinase enriches for a core protein identified as syndecan-1 by Western blot analysis, thus identifying a syndecan-1 binding site in the globular domain of laminin-1 and laminin-2. In summary, multiple interactions between laminin and HSG cells contribute to acinar differentiation, involving both beta1-integrins and syndecan-1.

Amino Acid Sequence↗

PubMed1981

Immunohistochemical localization of dipeptidyl aminopeptidase (DAP) IV in the rat submandibular gland during postnatal development.

The localization of dipeptidyl aminopeptidase (DAP) IV in the rat submandibular gland during postnatal development was studied immunohistochemically using the unlabeled antibody enzyme method. Cryostat sections of rat submandibular glands were examined in animals 1 to 50 days old. In the first postnatal week, faint immunoreaction was detected in the apical region of the cytoplasm of terminal tubules. During the second postnatal week the reaction was gradually restricted to the luminal region of terminal tubules or developing acinar cells, and its intensity increased. The most striking change of the enzyme localization was observed in 15-day-old rats. At this time, DAP IV was confined to the luminal and lateral membranes of differentiated acinar cells and to the luminal membranes of intercalated and striated duct cells. This localization pattern was similar to that of the adult animal. DAP IV activity in the gland was also measured biochemically during the postnatal development. The results were in agreement with those of the immunohistochemical study. These results suggest that the localization of DAP IV is closely related to the postnatal differentiation and proliferation of acinar cells.

Aging↗

PubMed1998

[Histochemical activity of dipeptidyl peptidase IV (DPP IV) in intracerebral transplantation of the submandibular gland in mice].

Histochemical activity of DPP IV in the intracerebral homotransplants of submandibular gland of the newborn mouse was investigated in the course of a 5-month period after transplantation. Eight weeks after grafting, the enzyme pattern in the parenchyma of transplants was already comparable with the enzyme pattern of a fully mature mouse submandibular gland in situ. At this time, DPP IV was active in the apicolateral cell membranes of numerous acini of the gland transplants. Enzyme activity in apical cell cytoplasm of granular convoluted tubules was found only in transplants located in the brain of male recipients.

Animals↗

PubMed1981

Hypertrophic and hyperplastic effects of thyroxine on the submandibular gland of the mouse.

The nature of the trophic response of the mouse submandibular gland to thyroxine (T4) was examined. Adult female Swiss-Webster mice were given daily subcutaneous injections of T4 (1 microgram/gm body weight) for two or four days; two injections of tritiated thymidine (3H-TdR) were given 24 and 29 hours after the last injection of hormone, and the mice were killed one hour after the last injection of 3H-TdR. One gland was analyzed chemically for DNA content and for incorporation of 3H-TdR, while the other was used to prepare autoradiograms. The cellular composition of each gland was analyzed by counting 1000 nuclei, and the frequency and labelling index (LI) of six cell types were established. A rise in specific activity of DNA and a fall in its concentration were seen in response to T4. The LI for the entire gland more than doubled. The LIs and frequencies of granular convoluted tubule and granular intercalated duct cells were increased more than those of acinar and nongranular intercalated duct cells; striated and excretory duct cells were not affected. It is concluded that the enlargement of the submandibular gland of the mouse caused by T4 is due to both hyperplastic and hypertrophic effects.

Animals↗