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PubMed2002

Pleomorphic adenoma of the submandibular gland: clinicopathological and immunohistochemical features of 60 cases in Brazil.

The submandibular gland is involved in only 5% to 10% of the salivary gland tumors, and pleomorphic adenoma (PA) is the most common tumor affecting it. This study describes the clinicopathological features and immunohistochemical expression of Ki-67 and p53 in 60 cases of submandibular salivary gland PAs. Most of the patients were in the third and fifth decades of life and 37 (62%) of them were women. Tumor sizes varied from 1 to 10 cm and the mean time between symptom onset and treatment was 52 months. Only 1 patient experienced local recurrence, 3 years after treatment. Histologically, most tumors consisted chiefly in a chondromyxoid stroma. Stroma-rich PAs were larger than stroma-poor ones (P<.02). All PAs were found negative for Ki-67 and p53. These results show that PAs of the submandibular gland are histologically similar to PAs of other salivary glands, and that they have a low proliferative rate and a good prognosis.

Adenoma, Pleomorphic↗
PubMed1994

Developmental changes in and hormonal modulation of epidermal growth factor concentration in the rat submandibular gland.

Developmental changes in the hormonal effects on the concentration of epidermal growth factor (EGF) in the rat submandibular gland were investigated. The level of EGF in the gland gradually increased with age from 4 up to 8 weeks of age; thereafter it increased markedly, reaching a plateau level at 12 weeks of age in both male and female rats. A significant sex difference in EGF levels was observed between 8 and 14 weeks, the level in the males being approximately twice as high as that in the females at 12 and 14 weeks of age. Castration of male rats decreased EGF to about the same level as that of control females. Treatment of castrated rats with testosterone propionate (TP) restored EGF to the levels in control male rats. Ovariectomy and/or administration of oestradiol-17 beta to ovariectomized rats had no apparent effect on EGF concentration. These findings indicate that the sex difference in EGF concentration can be attributed to the level of endogenous androgens. In addition, hypophysectomy of male rats caused a remarkable decrease in submandibular gland EGF to about 7% of the normal level. This reduction was significantly, although not completely, restored by the administration of TP, triiodothyronine (T3) or GH. Moreover, giving TP with T3 or with GH or both together had additive effects on the increase in EGF levels in hypophysectomized rats. These results provide evidence that EGF in the submandibular gland is regulated multihormonally by at least TP, T3 and GH.

Aging↗
PubMed1989

The immunohistolocalization of carbonic anhydrase III in the submandibular gland of rats and hamsters.

Carbonic anhydrase III has been localized using the avidin-biotin-glucose oxidase complex (ABC) method in the submandibular gland of the rat and hamster. This isozyme, which is predominant in skeletal muscle, was observed in intercalated duct, striated duct and excretory duct cells in the rat submandibular glands. In contrast, only some striated duct cells in hamster submandibular glands were stained.

Animals↗
PubMed1987

Early effects of alloxan on rat submandibular gland.

Early effects of alloxan on structure and function of rat submandibular gland were investigated by light and electron microscopy, X-ray microanalysis, and by analysis of secreted saliva. Alloxan induced, already within 3 h, intracellular accumulation of mucus, as also evidenced by an increase in the cellular calcium concentration. In addition, 3 to 6 h after injection of alloxan, the granular duct cells were found to be vacuolated, which could suggest a cytotoxic effect of alloxan on this cell type. Alloxan did not significantly affect the flow rate of submandibular saliva after pilocarpine stimulation, and also did not significantly alter the concentrations of sodium, potassium, calcium and protein in the final saliva. The effects of alloxan on the acinar cells of the rat submandibular gland and the absence of effects on fluid secretion by this gland are in accordance with a direct or indirect inhibition of the cAMP system.

Alloxan↗
PubMed1998

Topographical distribution of cells in the rat submandibular gland duct system with special reference to dark cells and tuft cells.

The duct system of the rat submandibular gland consists of the intercalated duct, the granular convoluted tubule, the striated duct, the excretory duct, the main excretory duct, and the salivary bladder. The duct system contains special cell types, such as dark cells and tuft cells, in addition to principal cells. However, little is known about cell distribution in the duct system. The purpose of the present study was to examine cell distribution and to perform a morphometric analysis of the duct system. Transmission and scanning electron microscopy were used to examine the duct system of the rat submandibular gland. Six regions in the duct system, the striated duct, the interlobular excretory duct, the 5-mm proximal excretory duct from the hilus, the main excretory duct at the hilus, the 10-mm distal main excretory duct from the hilus, and the salivary bladder, were investigated. Morphometric and statistical analyses of the data were then performed. The epithelium of the duct system consisted of a heterogeneous cell population. Dark cells and tuft cells were present throughout the duct system. The principal, dark, and tuft cells were distinguished by their different microvilli by using a scanning electron microscope. The frequency of these cells in the total epithelial cell population was as follows: The percentage of principal cells in the six regions of the duct system varied from 87.5% to 94.4%, that of dark cells varied from 4.1% to 7.2%, and that of tuft cells varied from 1.8% to 7.2%. The number of principal and tuft cells was significantly different between the striated duct and the main excretory duct at the hilus (P < 0.01). However, no significant difference in number of dark cells throughout the duct system was observed (P > 0.05). The abundance of the principal, dark, and tuft cells in the duct system of the rat submandibular gland was determined. Few tuft cells were distributed in the striated duct, and most were found at the hilus. Dark cells were distributed equally throughout the duct system.

Animals↗
PubMed1984

Methacholine-stimulated release of benzoyl-arginine-ethylester esterase from mouse submandibular gland cells.

The possible existence of cholinoceptor for inducing benzoyl-arginine-ethylester (BAEe) esterase release in the mouse submandibular gland was investigated using dispersed-cell preparations from normal male and female, castrated male and testosterone-treated female mice. Methacholine (a cholinoceptive agonist) induced esterase release only in normal female and castrated male mice, both of which had low esterase activity in the submandibular glands, whereas norepinephrine (an alpha-adrenoceptor agonist) induced esterase release in all of the mice. Methacholine-induced esterase release was completely inhibited by atropine, a cholinoceptive antagonist, but not by phenoxybenzamine, an alpha-adrenoceptor antagonist. The effects of metacholine and norepinephrine on esterase release were additive. The results suggest the coexistence of cholinoceptor and alpha-adrenoceptors for esterase release in the mouse submandibular gland. Calcium was essential for esterase release induced by either methacholine or norepinephrine.

Animals↗
PubMed1989

The regulation by thyroid hormones and androgen of epidermal growth factor synthesis in the submandibular gland and its plasma concentrations in mice.

The effects of androgen and thyroid hormones on epidermal growth factor (EGF) synthesis in the submandibular gland and on plasma EGF concentrations in mice were examined. Testosterone propionate was administered alone or in combination with L-thyroxine (T4) to female mice for 2 weeks. The submandibular EGF concentrations were increased by the administration of testosterone propionate in a dose-dependent fashion; the maximal increase, 20-fold, being produced by a dose of 2 mg every other day. The EGF levels were increased sevenfold by T4, which also enhanced the stimulatory effect of suboptimal doses of testosterone propionate. Cyproterone acetate, an anti-androgen, inhibited the testosterone propionate-induced increase, but not the T4-induced increase. Plasma EGF concentrations were raised by testosterone propionate but not by T4. Both hormones stimulated the accumulation of 4.7 kb preproEGF mRNA in the submandibular gland, which occurred almost in a parallel manner with the increase in submandibular EGF concentrations. These results suggest that EGF synthesis in the submandibular gland is regulated by alterations in the level of its mRNA by thyroid hormones and androgen, and that the rise in plasma EGF concentrations is under the influence of androgen but not of thyroid hormones.

Animals↗
PubMed1984

Malignant lymphoepithelial lesion of the submandibular gland.

A case of malignant lymphoepithelial lesion of the submandibular gland is reported and the literature is reviewed. This neoplasm has been described frequently in Eskimos and is usually located in the parotid gland. The histogenesis of the lesion is discussed. The tumor shows local aggressiveness, with frequent recurrences and metastases to regional lymph nodes. Surgical treatment consisting of wide resection of the tumor with regional lymph node dissection, with or without radiotherapy, seems to be the most appropriate therapy.

Aged↗
PubMed1984

Lectin-binding in premalignant lesions during submandibular gland carcinogenesis.

Complex carbohydrates in premalignant lesions of mouse submandibular gland tumors were examined by the lectin-peroxidase conjugate method. Peroxidase-conjugated lectins of PNA, RCA-1, DBA, SBA, UEA-1 and WGA were used to detect specific sugar residues of complex carbohydrates in premalignant lesions during experimental carcinogenesis. Marked reduction of PNA and SBA bindings occurred in duct-like structures and cystic lesions which were transformed from granular convoluted tubule cells. Premalignant lesions bound slightly to PNA, RCA-1, DBA, SBA and WGA and manifested increased UEA-1 binding. Squamous metaplastic epithelia of premalignant lesions manifested increased binding to PNA, RCA-1 and SBA as compared to those of duct-like structure and cystic epithelia.

Amino Sugars↗
PubMed2005

Na(+)/H(+) exchanger isoforms are differentially regulated in rat submandibular gland during acid/base disturbances in vivo.

Acute metabolic acidosis and alkalosis cause a series of homeostatic adaptive responses in the kidney and other epithelia. We hypothesized that acid/base disturbances might affect the expression of Na(+)/H(+) exchanger (NHE) isoforms in salivary glands and determined the expression and cellular distribution of NHE3 and NHE4 in rat submandibular glands of controls and after imposed acute or chronic metabolic acidosis or alkalosis in vivo. Reverse transcription/polymerase chain reaction, in situ hybridization, and immunohistochemistry were applied by using specific primers, antisense probes, and antibodies, respectively. The results showed NHE3 and NHE4 transcript expression and protein abundance in rat submandibular gland. NHE3 was apically localized in duct cells, whereas NHE4 was found basolaterally distributed in acinar and duct cells. Acute acidosis and alkalosis and chronic acidosis had no effect on NHE3 and NHE4 expression and localization. In contrast, chronic metabolic alkalosis significantly decreased the number of apically stained NHE3 duct cells but had no effect on NHE3 mRNA expression. The results demonstrate, for the first time, the presence of NHE4 protein in salivary glands. The data also indicate the distinct regulation and adaptive changes of different isoforms of the same transporter in rat submandibular gland as a response to acid/base disturbances.

Acid-Base Equilibrium↗
PubMed1989

Establishment and characterization of an epithelial cell line from the rat submandibular gland.

An epithelial cell line, RSMTx, has been established from the submandibular gland of weanling Fisher 344 rats by treatment of explanted tissue clumps with 3-methylcholanthrene. These cells exhibit a polygonal shape on light microscopy and a polar appearance, with desmosomes, terminal bar-like structures, surface microvilli and cytoplasmic interdigitations, when examined by electron microscopy. The cells react positively with an antiserum to cytoskeletal keratin, and a commercial monoclonal antibody to an "epithelial membrane antigen." An antiserum, prepared against early passage cells in hamsters, reacts primarily with ductal elements in tissue sections of submandibular gland, as does an antiserum prepared in mice with late passage cells. The cells are easily passaged and have been maintained for more than two years in continuous culture.

Actin Cytoskeleton↗
PubMed1987

A complete cDNA sequence for the major epidermal growth factor binding protein in the male mouse submandibular gland.

The complete cDNA sequence of the major epidermal growth factor binding protein (EGF-BP), isolated from the mouse submandibular gland, has been determined. Oligonucleotide probes complementary to unique, nonconserved, regions of homogeneous preparations of EGF-BP were used to identify the correct cDNA clone from a male mouse submandibular gland cDNA library. The nucleotide sequence codes for a glandular kallikrein that is the main arginine esterase complexed with epidermal growth factor. The mRNA coding for this EGF-BP is estimated at 0.24% of the total mRNA of the adult male mouse submandibular gland, thus representing an abundant member of the kallikrein family in this tissue. In addition, the cDNA sequence defines a putative transcription start site. The reported cDNA sequence is clearly different from, and not an allelic form of, a previously reported cDNA sequence for EGF-BP. The present work reconciles conflicting information in the literature regarding the identity of EGF-BP.

Amino Acid Sequence↗
PubMed1987

Sexual difference in properties of 5 alpha-reductase in microsome of rat submandibular glands.

The properties of 5 alpha-reductase activity in the submandibular glands of rats were investigated using microsomal fraction in the presence of NADPH, and we found a sexual difference in these properties. The formation of 5 alpha-dihydrotestosterone and 5 alpha-androstane-3 alpha, 17 beta-diol from testosterone demonstrated 5 alpha-reductase in the rat microsomal fraction of this tissue sample. Apparent michaelis constants (Km) of the 5 alpha-reductase activity for testosterone was 1.02 x 10(-6) M for the female tissue. Microsomal fraction of submandibular glands of male rats had two Kms and were determined as 1.12 x 10(-6) M and 1.01 x 10(-5) M. The lower Km of 5 alpha-reductase for male rats was similar to for the females.

Animals↗
PubMedDate not supplied

Immunoregulatory effects of glandular kallikrein from the salivary submandibular gland of rats.

A protein of 40 kD molecular weight was isolated from the salivary submandibular glands of male rats. The protein catalyzed the hydrolysis of alpha-N-benzoyl-L-arginine ethyl ester. This esterase activity was inhibitable with the protease inhibitor aprotinin. The sequence of the first 25 amino acids of this protein was identical to that of rat glandular kallikrein (rGK). When added to cultures of murine lymph node cells suboptimally stimulated with the T cell mitogen concanavalin A, rGK markedly stimulated the proliferative activity of these cells. When injected into mice, rGK suppressed the contact sensitivity response to picryl chloride, a form of delayed-type hypersensitivity. Similar in vitro and in vivo effects were induced with GK from porcine pancreas (pGK). Moreover, the aforementioned in vitro and in vivo effects were abolished by aprotinin either added to the tissue culture medium or injected into the animals immediately before rGK or pGK. This demonstrates that the enzymatic activity of rGK and pGK is important for the induction of immunoregulatory effects. These results suggest that rGK is a systemic immunoregulatory enzyme with immunosuppressive potential. GK is the first example for systemic immunoregulation by an enzyme, the secretion of which is under neuroendocrine control.

Amino Acid Sequence↗
PubMed2000

Apoptosis and mitosis of parenchymal cells in the duct-ligated rat submandibular gland.

Apoptosis and proliferation of parenchymal cells during atrophy of rat submandibular gland induced by double duct ligation were investigated using immunohistochemistry for proliferating cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labelling (TUNEL) and transmission electron microscopy (TEM). At 2 and 3 days after ligation, increased PCNA positive cells and mitoses were seen in ducts; thereafter PCNA positive cells decreased in number. At 3 and 4 days, the acinar cell population rapidly decreased, with many remaining TUNEL positive acinar cells. During this period, TEM showed typical apoptotic acinar cells that were phagocytosed by adjacent acinar cells or intraepithelial macrophages. After 7 days, most acinar cells had disappeared, leaving prominent residual ducts; a few acinar cells remained, especially at the lobule periphery. Submandibular gland duct ligation thus induced marked depletion of acinar cell by apoptosis and a concurrent short-lived cycle of duct cell proliferation.

Animals↗
PubMed1987

Evaluation of submandibular gland function by sialo-scintigraphy following sialolithectomy.

Submandibular gland function following transoral sialolithectomy was examined by 99mTc-pertechnetate sialo-scintigraphy in 10 cases. An intraindividual comparison between the function of the treated gland and that of the contralateral normal gland was made using a time-activity curve. Although glandular recovery was not affected by the duration of symptoms or the existence of the symptom at mealtimes, it was inversely proportional to the size of the calculus. Furthermore, the prognosis was more favorable in patients when the anatomically normal orifice of the submandibular duct was preserved.

Adolescent↗
PubMed2001

Immunolocalization of PTHrP in the submandibular glands of three rodent species.

The present study deals with immunohistochemical localization of PTHrP in bank vole, pine vole and white mouse submandibular glands. PTHrP immunoreactivity was observed in epithelial cells of all ductal segments (intercalated, striated, interlobular and main excretory ducts) of the salivary glands in all the three animal species tested. We also found PTHrP expression in myoepithelial cells surrounding the mucous alveoli of submandibular glands in those animals. The reaction was less intense than that found in the epithelial cells of excretory ducts. We occasionally observed a very slight positive reaction for PTHrP in smooth muscle cells of small blood vessels. We also found PTHrP expression in the neurons of ganglion in the submandibular gland.

Animals↗
PubMed1983

A new esteroproteinase (proteinase F) from the submandibular glands of female mice.

One of the esteroproteinases present in the submandibular glands of female mice was purified and characterized. The enzyme, designated proteinase F in this report, had a pI value of 4.6 and a molecular weight of 27600, being comprised of two subunits of 10000 and 18000 daltons. The amino acid composition of proteinase F resembled that of the epidermal growth factor-binding protein, but antiserum against proteinase F only reacted weakly against the binding protein. Proteinase F had an optimum pH at around 9.0 and was strongly inhibited by Cu2+ and Hg2+ (42 and 76% inhibition, respectively, at a concentration of 4 x 10(-6) M). It was also inhibited by aprotinin, phenylmethylsulfonylfluoride, iodoacetamide, leupeptin, antipain, and benzamidine but neither by trypsin inhibitors from pancrease, soybean, or ovomucoid, nor by TLCK, TPCK, and epsilon-amino-n-caproic acid. Although its actual physiological function has yet to be determined, these properties indicate that proteinase F is a new enzyme, being distinguished from known proteinases, kallikrein, plasmin, trypsin, chymotrypsin, tonin, angiotensin-converting enzyme, proteinase A (beta-nerve growth factor endopeptidase), proteinase D (epidermal growth factor-binding protein), P-esterase, renin A, and renin C. Proteinase F was present in the submandibular glands of female mice more abundantly than in those of males, but it increased in males following castration. Thus, proteinase F appears to be affected by male hormones in vivo.

Amino Acids↗