[Salivary duct carcinoma].
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The progression of benign cystic lesions of the parotid gland to malignant tumors is an extremely rare event and has been described only for cystadenolymphomas. Here we present a case of malignant transformation to an adenocarcinoma occurring in ductal cells forming the wall of a parotid retention cyst. In addition to clinical and histological findings, we describe the results of immunohistochemical and molecular analyses providing evidence that the cells undergoing neoplastic transformation were latently infected by Epstein-Barr virus (EBV). These results suggest a possible causal relationship between latent EBV infection and malignant progression.
GPRCs are regulated via phosphorylation by different protein kinases including GRKs and PKA and PKC. The purpose of this study was to determine the presence and physiological role of GRKs in the tissues of the snail, Helix pomatia. Here we report that immunoblotting of brain homogenate with anti-GRK2/3 antibody prepared from mammalian tissue can be detected in snail GRK-like immunoreactivity. The GRK2/3 immunoreactivity was found at approximately 80 kDa in a variety of cells, including salivary duct, salivary gland and eye. Intracellular injection of the anti-GRK2/3 prevented the neuron from desensitization and agonist-induced activation augmented the phosphorylated GRKs in the membrane fraction suggesting that GRKs may have a functional role in the neuropeptide receptor desensitization in snail.
Internal and external head structures of males of Strepsiptera were examined and the head of a species of Mengenilla is described in detail. The results suggest a reinterpretation of some structures. The head of basal extant strepsipterans is subprognathous, whereas it is strictly orthognathous in the groundplan of Strepsiptera s.l. The labrum and hypopharynx are not part of the mouthfield sclerite. The labial palps are absent in all strepsipterans. A very slightly modified mandibular articulation is preserved in Eoxenos, whereas it is distinctly reduced in other extant groups. A salivary duct, salivary glands, and a cephalic aorta are absent. The cladistic analysis of 44 characters of the head results in the following branching pattern: (Protoxenos + (Mengea + (Eoxenos + (Mengenilla [Austr.] + Mengenilla) + (Elenchus + Dundoxenos + Xenos + Stylops)))). Most apomorphies of males are associated with the necessity of finding females within a short time span and with a reduced necessity to consume food: large "raspberry" eyes, flabellate antennae with numerous dome-shaped chemoreceptors, Hofeneder's organ, an ovoid sensillum of the maxillary palp, and the simplified condition of the maxilla and the labium. Strepsiptera excl. Protoxenos are supported by the dorsomedian frontal impression, the dorsally shifted antennal insertions, a reduced number of antennal segments, absence of the galea, and probably by the presence of the mouthfield sclerite, which is a unique apomorphic feature. The balloon-gut combined with an unusual air-uptake apparatus is another possible autapomorphy of this clade. It is likely that the last common ancestor of Strepsiptera excl. Protoxenos did not process food. Strepsiptera s.str. are characterized by the strongly reduced condition of the labrum and the absence of the epistomal suture. Eoxenos is the sister group of the remaining Strepsiptera s.str. Synapomorphies of Mengenilla + Stylopidia are the advanced reduction of the mandibular articulation and the secondary absence of the ovoid sensillum. The monophyly of Mengenilla is confirmed, even though a small free labrum is present in Australian species. Derived features of Stylopidia are the absence of the coronal suture and the reduced condition of the frontal suture. Apomorphies that have evolved within Stylopidia are the membranization of parts of the head, the fusion of antennal segments, the increase or decrease of the number of flabellate flagellomeres, reductions and modifications of the mandibles, and modifications of the mouthfield sclerite. The monophyly of Stylopiformia is not unambiguously supported. A position of the mandibles posterior to the mouthfield sclerite (when adducted) is a possible synapomorphy shared by Xenos, Stylops, and other "higher Stylopidia." The blade-like distal part of the mandibles suggests a closer relationship of Elenchus with these taxa.
In order to introduce the microsurgical technique of suturing the salivary ducts' lesions, microsurgical anatomy of ducts draining large salivary glands was studied in 12 human autopsies and 10 dogs. Experimental surgery was performed in 10 dogs: the sectioned parotid and submandibular ducts were repaired. Sialographic evidence of recanalization was obtained in 8 of the dogs. Histological investigation showed minimal inflammatory response within 20 to 60 days after surgery.
1. To characterize [Ca2+]i signalling in salivary duct cells a procedure was developed for the rapid preparation and isolation of intralobular ducts, some of which had attached intercalated ducts. The isolated ducts retained agonist-induced Ca2+ signalling after permeabilization with streptolysin O (SLO). 2. The improved cell preparation technique was reflected in the repertoire and intensity of agonist responsiveness of the cells. Measurements of [Ca2+]i in intact cells showed that all agonists previously reported to affect electrolyte transport by the submandibular salivary gland (adrenaline, carbachol, isoprenaline and forskolin) mobilized Ca2+ from internal stores and increased Ca2+ influx across the plasma membrane. 3. The use of the SLO-permeabilized ducts showed that all agonists, including isoprenaline and forskolin, mobilized Ca2+ exclusively from the inositol 1,4,5 trisphosphate (IP3)-sensitive pool. However, in granular ducts only adrenaline mobilized the entire IP3-sensitive pool whereas all other agonists mobilized only part of the pool. 4. All regions of the duct responded to substance P and the luminally secreted agonist ATP. Interestingly, the intercalated duct was most responsive to ATP and demonstrated only a minimal response to all other agonists. The granular region of the same duct and the extralobular duct always responded best to stimulation by adrenaline. 5. The perfused extralobular duct was used to show that adrenaline and carbachol stimulated the duct through the basolateral membrane whereas the receptors for ATP were localized in the luminal membrane of the duct. This suggests the presence of an ATP-dependent positive feedback loop in salivary duct with decreased activity along the ductal tree.
Observations were made in sheep, before and after fresh food was given during teasing with food and after rumination, on the flow of parotid saliva and its protein Mg2+, K+, Na+ and Cl- concentrations. The animals studied had either a cannulated or fistulated parotid salivary duct. Parotid salivary flow, protein, Mg2+, K+ and Cl- increased markedly following feeding. The increases in protein and Mg2+, but not in flow, were largely blocked by the i.v. administration of propranolol (1 mg . kg-1). Whereas the actual ingestion of food was associated with large increases in protein (up to 42.5 times, to as high as 1760 micrograms . ml-1 of saliva), teasing with food caused relatively minor increases in parotid saliva. There were slight, if any, changes in protein concentration during the increased parotid salivary flows of rumination, whether chewing was on the same side or contralateral to the cannulated parotid salivary duct. It is concluded that a beta-adrenergic mechanism previously demonstrated in acute experiments contributes to increases in the secretion of protein of the parotid saliva when sheep eat. There was a close correlation between the concentrations of protein and of Mg2+ but not of the other electrolytes studied.
The salivary system in mammals is comprised of three independently developed pairs of organs, the parotid, submaxillar, and sublingual glands. Each gland is composed of various ductal and acinar cell types that fulfill multiple roles. However, the molecular mechanisms regulating their biogenesis and functions are still largely unknown. In this paper, we report that two class B basic helix-loop-helix (bHLH) transcriptional regulators delineate the ductal and the acinar cells in salivary glands. Sgn1, a novel class B bHLH factor, is specifically expressed in the salivary duct cells, while the acinar cells are characterized by the expression of another class B bHLH factor, Mist1. The molecular nature of Sgn1 was also investigated: it binds to specific sequences of DNA as a dimer with a class A bHLH factor and acts as a negative transcriptional regulator against other bHLH factors. This study provides an important cue towards better understanding of the generation and function of multiple cell types in salivary glands. In addition, Sgn1 expression exhibits a reverse relationship with the development of male phenotypes, suggesting its role in gender dimorphism in the salivary glands.
Intralobular (granular) salivary ducts were purified by isopycnic centrifugation after collagenase/hyaluronidase digestion of the rat submandibular gland. The resulting ductal fraction (density, 1.056 +/- 0.003) was highly enriched in kallikrein (a ductal cell marker) and contained little amylase activity (an acinar cell marker). The resting intracellular calcium level in the ductal preparation was 103 +/- 4 nM. Increased intracellular calcium concentrations (2-3 times resting levels) were observed in response to muscarinic (carbachol) and alpha-adrenergic (epinephrine) agonists, but little response was observed to substance P, suggesting the absence of substance P peptidergic receptors on rat submandibular ducts. Intracellular adenosine 3',5'-cyclic monophosphate levels were increased 35-fold in response to beta-adrenergic stimulation (isoproterenol) and forskolin. The ducts secreted kallikrein in response to epinephrine, carbachol, and isoproterenol but not in response to substance P. Epinephrine was the most potent inducer of kallikrein release with a K0.5 of approximately 3 microM and a maximal secretory rate approximately nine times unstimulated levels. Taken together, these results provide strong evidence for the functional integrity of the ductal preparation. This preparation should prove useful for the further elucidation of the properties of intralobular salivary ducts structures which heretofore have only been studied indirectly.
Usual imaging diagnostic for salivary glands is sialography. Sialography is not stripped of disadvantages and failures. The MRI-sialography is an examination which is carried out without any injection of contrast's product (without catheterization or intravenous injection). It is thus noninvasive and painless. The complete study of salivary gland and its ducts is always possible and could not be blocked by local or loco-regional conditions. It allows exploration of several salivary glands in the same time. We think that the MRI-sialography must find its place in the diagnosis arsenal for salivary pathology in spite of its current handicaps represented by its cost and the difficulty of access to the apparatuses.
A neoplastic human salivary intercalated duct cell clone was cultured in 5 microM 5-azacytidine for 5 days at 37 degrees C; then the cells were trypsinized and subcultured in growth medium without 5-azacytidine. Thereafter, subclones were cloned from the subculture. Of 12 subclones isolated, 7 clonal cell lines were established and characterized. The two subclones composed of cells which were spindle shaped or stellate exhibited phenotypes similar to those of myoepithelial cells such as microfibrils and myosin and formed a myoepithelioma upon transplantation of the cells into nude mice. The other five subclones were composed of polygonal cells with numerous secretory granules in their cytoplasm and containing amylase that seems to be specific to acinar cells; transplantation of these cells into nude mice resulted in production of acinic cell carcinoma. These findings indicate that a neoplastic human salivary intercalated duct cell is capable of at least bidirectional differentiation.
Salivary glands of adult male and female Culicoides variipennis (Coquillett) were sexually dimorphic when examined by phase contrast light microscopy. Female salivary glands were larger and more complex than those in males. Each female gland consisted of a main gland, which was subdivided into a proximal neck and a distal body with reference to the salivary duct, and four accessory glands. Each male salivary gland consisted of a pear-shaped body with a constriction, or neck, that divided it into a proximal and a distal portion, with reference to the salivary duct. Salivary glands of both sexes increased in length from emergence to day 3, followed by a sex-specific pattern of decrease. Based on these morphological observations, we suggest that the salivary glands of female C. variipennis are specialized in the production of secretory materials for blood-feeding.
From previous immunofluorescent, immunohistochemical and ultrastructural studies, myoepithelial cells have been reported to be absent from the striated and excretory ducts of human salivary gland. Yet recently, certain anti-cytokeratin monoclonal antibodies which specifically label the myoepithelium of salivary gland acini and intercalated ducts have also been found to stain basally situated cells in both striated and excretory ducts. In this study, we have used eight samples of normal human parotid gland (methacarn-fixed and frozen sections) to establish if basal cells of striated and excretory ducts have the cytoskeletal protein complement (actin and cytokeratins) of myoepithelial cells. Using a muscle-specific actin, HHF35, not only is the myoepithelium of acini and intercalated ducts stained in all cases, but stellate and spindle shaped cells are also detected all along the inter- and intralobular striated ducts in four of the eight examples. With double-labeled frozen sections and fluorescent microscopy, the actin-specific probe, phalloidin, and the myoepithelial-selective anti-cytokeratin 14 antibody, 312C8-1, confirm that the striated duct does have a population of basal cells with the cytoskeletal protein make-up of myoepithelium. The monoclonal antibody 8.12 (specific for cytokeratin 13 and 16) also stains some basal cells of striated and excretory ducts, as well as luminal cells of ducts at all levels, but does not label the myoepithelium of acini and intercalated ducts. Both the anti-cytokeratin antibodies and the actin-detecting mechanisms reveal that the basal cell population of striated and excretory ducts is more heterogeneous, and likely functionally more complex, than has been realized previously. Such findings are not in agreement with certain aspects of current theories of the histogenesis of salivary gland tumours.
In order to facilitate studies on human salivary glands, a method was developed for the culture of minor salivary gland duct cells from tissues obtained from oral surgery protocols. Minor salivary glands were isolated from such tissues, and a serum-free growth medium was developed which supported the growth of the ductal component of these glands. The ductal origin of these cells was confirmed through immunohistochemical localization of replicating nuclei through incorporation of BrdU. The presence of epidermal keratin in replicating cells and the absence of smooth muscle myosin further substantiated the ductal origin of cells. Using normal growth medium calcium concentrations (1.05 mM), these cells produced a keratinized multilayer of cells unable to undergo routine subculture procedures. A reduction in calcium ion concentration to 0.1 mM resulted in a cell monolayer, without evidence of terminal keratinization, which could undergo at least eight serial passages (1:3 ratio) under cell culture conditions. It is advanced that these minor salivary gland duct cell cultures will be of use to those studying diseases and disorders of the salivary glands.
BACKGROUND: We previously reported that Fas antigen was strongly expressed on salivary duct epithelial cells and that some salivary infiltrating cells showed the Fas ligand in patients with severe sialoadenitis due to Sjögren's syndrome (SS). Apoptotic changes were observed in ductal epithelial cells and some infiltrating cells by DNA nick end labeling methods. These findings suggest that the Fas-Fas ligand system may play a role in the pathogenesis of sialoadenitis in SS. OBJECTIVE: To elucidate the mechanism of the de novo expression of ductal Fas antigen in sialoadenitis associated with SS, we investigated the induction of Fas antigen and apoptosis by cytokines in a human salivary duct cell line. METHODS: Human salivary duct cell line (HSG) was cultured with interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2), interleukin 4 (IL-4), and granulocyte monocyte colony stimulating factor (GM-CSF). The expression of Fas antigen in HSG was examined by immunoperoxidase cell ELISA. The appearance of DNA strand breaks during apoptosis induced by anti-Fas antibody was detected by DNA nick end labeling methods. RESULTS: Unstimulated HSG cells constitutively expressed low levels of Fas antigen. IFN-gamma and TNF-alpha consistently upregulated constitutive levels of Fas. In contrast, IL-1 beta, IL-2, IL-4, and GM-CSF had no effect on Fas levels. HSG cells expressing Fas antigen in response to IFN-gamma or TNF-alpha were susceptible to apoptosis by anti-Fas antibody. CONCLUSION: Our findings suggest that IFN-gamma or TNF-alpha secreted by infiltrating lymphocytes induces ductal Fas expression and ductal apoptosis in sialoadenitis associated with SS.
PURPOSE: This article describes the use of sialoendoscopy for diagnosis and treatment of strictures and kinks in the major salivary glands ducts. PATIENTS AND METHODS: Thirty-four salivary glands with obstruction were diagnosed as having ductal kinks or strictures. Strictures were diagnosed by sialography and sialoendoscopy, kinks were diagnosed mainly by sialography, whereas endoscopy was used to rule out other pathology and to locate the kink. There were strictures in 25 salivary glands (14 male and 11 females; aged 25 to 60 years), 14 in the parotid and 11 in the submandibular gland, and kinks in 9 salivary glands (5 males 4 females; aged 40 to 55 years). Seven kinks were found in the submandibular gland and 2 in the parotid. Treatment of strictures was performed by dilatation procedures with saline under pressure, balloon techniques, and forced manipulation. After these procedures, a polyethylene stent was inserted for 2 weeks. Kinks were treated by advancement ductoplasty and balloon contouring to overcome the acute angle. RESULTS: Twenty of 25 cases of stricture became completely asymptomatic in a follow-up of 8 to 36 months after treatment. In 4 cases, further revisional dilatation was needed, and in 1 case treatment failed and the gland had to be removed. All 9 cases of kinks became completely asymptomatic in a follow-up of 6 to 24 months after treatment. CONCLUSION: Strictures and kinks should be considered when salivary gland obstruction is present without sialolithiasis.
The purpose of this study was to examine the effect of glucocorticoid on human neoplastic salivary duct epithelial cell line (HSG). Dexamethasone was found to inhibit cell growth and to increase cell size and the ratio of protein content to DNA content in a cell. The inhibition of cell growth was dose-dependent; in comparison to the control (33.8 +/- 3.1 h), the population doubling time was 1.57-fold longer in 10(-5) M dexamethasone (P less than 0.01, N-K test). [3H] thymidine incorporation was inhibited in 45.5% of the control at 10(-5) M. Plating efficiency was 20.5 +/- 3.0% in 10(-5) M and 47.0 +/- 4.4% in the absence of dexamethasone. Cell diameters increased 1.29 fold in 10(-5) M dexamethasone in comparison to the control size (16.0 +/- 2.1 micron). The ratio of total protein content of DNA content increased 1.46 fold in 10(-5) M dexamethasone-treated cells on the seventh day of cultivation. Scatchard plot analysis using [6, 7-3H]-triamcinolone revealed that the HSG cells had apparent cytosolic glucocorticoid receptors with an equilibrium dissociation constant (Kd value) of 6.48 nM, whose number of binding sites (NBS) was 57.8 fmol/mg protein.
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