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Sample records for rabbit parotid acinar

  1. Ca2+-activated K channels in parotid acinar cells

    PubMed Central

    Romanenko, Victor G; Thompson, Jill

    2010-01-01

    Fluid secretion relies on a close interplay between Ca2+-activated Cl and K channels. Salivary acinar cells contain both large conductance, BK, and intermediate conductance, IK1, K channels. Physiological fluid secretion occurs with only modest (<500 nM) increases in intracellular Ca2+ levels but BK channels in many cell types and in heterologous expression systems require very high concentrations for significant activation. We report here our efforts to understand this apparent contradiction. We determined the Ca2+ dependence of IK1 and BK channels in mouse parotid acinar cells. IK1 channels activated with an apparent Ca2+ affinity of about 350 nM and a hill coefficient near 3. Native parotid BK channels activated at similar Ca2+ levels unlike the BK channels in other cell types. Since the parotid BK channel is encoded by an uncommon splice variant, we examined this clone in a heterologous expression system. In contrast to the native parotid channel, activation of this expressed “parslo” channel required very high levels of Ca2+. In order to understand the functional basis for the special properties of the native channels, we analyzed the parotid BK channel in the context of the horrigan-Aldrich model of BK channel gating. We found that the shifted activation of parotid BK channels resulted from a hyperpolarizing shift of the voltage dependence of voltage sensor activation and channel opening and included a large change in the coupling of these two processes. PMID:20519930

  2. A Systems Biology Approach Identifies a Regulatory Network in Parotid Acinar Cell Terminal Differentiation

    PubMed Central

    Metzler, Melissa A.; Venkatesh, Srirangapatnam G.; Lakshmanan, Jaganathan; Carenbauer, Anne L.; Perez, Sara M.; Andres, Sarah A.; Appana, Savitri; Brock, Guy N.; Wittliff, James L.; Darling, Douglas S.

    2015-01-01

    Objective The transcription factor networks that drive parotid salivary gland progenitor cells to terminally differentiate, remain largely unknown and are vital to understanding the regeneration process. Methodology A systems biology approach was taken to measure mRNA and microRNA expression in vivo across acinar cell terminal differentiation in the rat parotid salivary gland. Laser capture microdissection (LCM) was used to specifically isolate acinar cell RNA at times spanning the month-long period of parotid differentiation. Results Clustering of microarray measurements suggests that expression occurs in four stages. mRNA expression patterns suggest a novel role for Pparg which is transiently increased during mid postnatal differentiation in concert with several target gene mRNAs. 79 microRNAs are significantly differentially expressed across time. Profiles of statistically significant changes of mRNA expression, combined with reciprocal correlations of microRNAs and their target mRNAs, suggest a putative network involving Klf4, a differentiation inhibiting transcription factor, which decreases as several targeting microRNAs increase late in differentiation. The network suggests a molecular switch (involving Prdm1, Sox11, Pax5, miR-200a, and miR-30a) progressively decreases repression of Xbp1 gene transcription, in concert with decreased translational repression by miR-214. The transcription factor Xbp1 mRNA is initially low, increases progressively, and may be maintained by a positive feedback loop with Atf6. Transfection studies show that Xbp1Mist1 promoter. In addition, Xbp1 and Mist1 each activate the parotid secretory protein (Psp) gene, which encodes an abundant salivary protein, and is a marker of terminal differentiation. Conclusion This study identifies novel expression patterns of Pparg, Klf4, and Sox11 during parotid acinar cell differentiation, as well as numerous differentially expressed microRNAs. Network analysis identifies a novel stemness arm, a

  3. Long-term dexamethasone treatment alters the histomorphology of acinar cells in rat parotid and submandibular glands

    PubMed Central

    Bighetti, Bruna B; Assis, Gerson F d; Vieira, Danilo C; Violato, Natalia M; Cestari, Tania M; Taga, Rumio; Bosqueiro, José R; Rafacho, Alex

    2014-01-01

    Glucocorticoids (GCs) induce insulin resistance (IR), a condition known to alter oral homeostasis. This study investigated the effects of long-term dexamethasone administration on morphofunctional aspects of salivary glands. Male Wistar rats received daily injections of dexamethasone [0.1 mg/kg body weight (b.w.), intraperitoneally] for 10 days (DEX), whereas control rats received saline. Subsequently, glycaemia, insulinaemia, insulin secretion and salivary flow were analysed. The parotid and submandibular glands were collected for histomorphometric evaluation and Western blot experiments. The DEX rats were found to be normoglycaemic, hyperinsulinaemic, insulin resistant and glucose intolerant (P < 0.05). DEX rat islets secreted more insulin in response to glucose (P < 0.05). DEX rats had significant reductions in the masses of the parotid (29%) and submandibular (16%) glands (P < 0.05) that was associated with reduced salivary flux rate. The hypotrophy in both glands observed in the DEX group was associated with marked reduction in the volume of the acinar cells in these glands of 50% and 26% respectively (P < 0.05). The total number of acinar cells was increased in the submandibular glands of the DEX rats (P < 0.05) but not in the parotid glands. The levels of proteins related to insulin and survival signalling in both glands did not differ between the groups. In conclusion, the long-term administration of dexamethasone caused IR, which was associated with significant reductions in both mass and flux rate of the salivary glands. The parotid and submandibular glands exhibited reduced acinar cell volume; however, the submandibular glands displayed acinar hyperplasia, indicating a gland-specific response to GCs. Our data emphasize that GC-based therapies and insulin-resistant states have a negative impact on salivary gland homeostasis. PMID:25186305

  4. Parasympathetic non-adrenergic, non-cholinergic mechanisms in reflex secretion of parotid acinar granules in conscious rats.

    PubMed Central

    Ekström, J; Helander, H F; Tobin, G

    1993-01-01

    1. Female adult rats were subjected to sympathetic denervation of the parotid glands by bilateral removal of the superior cervical ganglion 10-12 days before acute experiments. The sympathectomy was in some of the experimental groups combined with either bilateral adrenal medullectomy, treatment with the sensory neurotoxin capsaicin or parasympathetic denervation of the gland by cutting the auriculotemporal nerve. 2. Food but not water was withheld for 29-32 h before acute experiments. All animals were given an intraperitoneal injection of phentolamine (2 mg kg-1) and propranolol (1 mg kg-1) and, when appropriate, also atropine (1 mg kg-1). Then the experimental animals were fed their ordinary food of hard chow for 60-90 min. Thereafter, these animals and their non-fed controls were killed, and the parotid glands were removed and used for either morphometric assessment or measurement of amylase activity. 3. In the atropinized rats subjected to sympathectomy alone, eating reduced the numerical density of acinar secretory granules by 50% and the total activity of amylase by 55%; the corresponding figures were, when sympathectomy was combined with adrenal medullectomy, 51 and 63%. Also, in atropinized animals subjected to sympathectomy and capsaicin pretreatment, eating reduced the numerical density of acinar granules and the total amylase activity, in this case by 45 and 35%, respectively. 4. In the atropinized rats subjected to sympathectomy and parasympathectomy, eating caused no change in the numerical density of acinar granules but reduced the total amylase activity by 35%. 5. In the non-atropinized rats subjected to sympathectomy alone, eating reduced the numerical density of acinar granules by 22%, while there was no change in the total amylase activity. 6. In conclusion, eating evoked a reflex activation of the sympathectomized parotid gland that engaged non-adrenergic non-cholinergic receptors of the acinar cells. The present results give weight to a

  5. Agonist activation of arachidonate-regulated Ca2+-selective (ARC) channels in murine parotid and pancreatic acinar cells.

    PubMed

    Mignen, Olivier; Thompson, Jill L; Yule, David I; Shuttleworth, Trevor J

    2005-05-01

    ARC channels (arachidonate-regulated Ca(2+)-selective channels) are a novel type of highly Ca(2+)-selective channel that are specifically activated by low concentrations of agonist-induced arachidonic acid. This activation occurs in the absence of any depletion of internal Ca(2+) stores (i.e. they are 'non-capacitative'). Previous studies in HEK293 cells have shown that these channels provide the predominant pathway for the entry of Ca(2+) seen at low agonist concentrations where oscillatory [Ca(2+)](i) signals are typically produced. In contrast, activation of the more widely studied store-operated Ca(2+) channels (e.g. CRAC channels) is only seen at higher agonist concentrations where sustained 'plateau-type'[Ca(2+)](i) responses are observed. We have now demonstrated the presence of ARC channels in both parotid and pancreatic acinar cells and shown that, again, they are specifically activated by the low concentrations of appropriate agonists (carbachol in the parotid, and both carbachol and cholecystokinin in the pancreas) that are associated with oscillatory [Ca(2+)](i) signals in these cells. Uncoupling the receptor-mediated activation of cytosolic phospholipase A(2) (cPLA(2)) with isotetrandrine reduces the activation of the ARC channels by carbachol and, correspondingly, markedly inhibits the [Ca(2+)](i) signals induced by low carbachol concentrations, whilst those signals seen at high agonist concentrations are essentially unaffected. Interestingly, in the pancreatic acinar cells, activation by cholecystokinin induces a current through the ARC channels that is only approximately 60% of that seen with carbachol. This is consistent with previous reports indicating that carbachol-induced [Ca(2+)](i) signals in these cells are much more dependent on Ca(2+) entry than are the cholecystokinin-induced responses.

  6. Distinct contributions by ionotropic purinoceptor subtypes to ATP-evoked calcium signals in mouse parotid acinar cells

    PubMed Central

    Bhattacharya, Sumit; Verrill, Douglas S; Carbone, Kristopher M; Brown, Stefanie; Yule, David I; Giovannucci, David R

    2012-01-01

    There is emerging consensus that P2X4 and P2X7 ionotropic purinoceptors (P2X4R and P2X7R) are critical players in regulating [Ca2+]i dynamics and fluid secretion in the salivary gland. In contrast, details regarding their compartmentalization and selective activation, contributions to the spatiotemporal properties of intracellular signals and roles in regulating protein exocytosis and ion channel activity have remained largely undefined. To address these concerns, we profiled mouse parotid acinar cells using live-cell imaging to follow the spatial and temporal features of ATP-evoked Ca2+ dynamics and exocytotic activity. Selective activation of P2X7Rs revealed an apical-to-basal [Ca2+]i signal that initiated at the sub-luminal border and propagated with a wave speed estimated at 17.3 ± 4.3 μm s−1 (n = 6). The evoked Ca2+ spike consisted of Ca2+ influx and Ca2+-induced Ca2+ release from intracellular Ca2+ channels. In contrast, selective activation of P2X4Rs induced a Ca2+ signal that initiated basally and propagated toward the lumen with a wave speed of 4.3 ± 0.2 μm s−1 (n = 8) that was largely independent of intracellular Ca2+ channel blockade. Consistent with these observations, P2X7R expression was enriched in the sub-luminal regions of acinar cells while P2X4R appeared localized to basal areas. In addition, we showed that P2X4R and P2X7R activation evokes exocytosis in parotid acinar cells. Our studies also demonstrate that the P2X4R-mediated [Ca2+]i rise and subsequent protein exocytosis was enhanced by ivermectin (IVR). Thus, in addition to furthering our understanding of salivary gland physiology, this study identifies P2X4R as a potential target for treatment of salivary hypofunction diseases. PMID:22451435

  7. Low-level (gallium-aluminum-arsenide) laser irradiation of Par-C10 cells and acinar cells of rat parotid gland.

    PubMed

    Onizawa, Katsuhiro; Muramatsu, Takashi; Matsuki, Miwako; Ohta, Kazumasa; Matsuzaka, Kenichi; Oda, Yutaka; Shimono, Masaki

    2009-03-01

    We investigated cell response, including cell proliferation and expression of heat stress protein and bcl-2, to clarify the influence of low-level [gallium-aluminum-arsenide (Ga-Al-As) diode] laser irradiation on Par-C10 cells derived from the acinar cells of rat parotid glands. Furthermore, we also investigated amylase release and cell death from irradiation in acinar cells from rat parotid glands. The number of Par-C10 cells in the laser-irradiated groups was higher than that in the non-irradiated group at days 5 and 7, and the difference was statistically significant (P < 0.01). Greater expression of heat shock protein (HSP)25 and bcl-2 was seen on days 1 and 3 in the irradiated group. Assay of the released amylase showed no significant difference statistically between the irradiated group and the non-irradiated group. Trypan blue exclusion assay revealed that there was no difference in the ratio of dead to live cells between the irradiated and the non-irradiated groups. These results suggest that low-level laser irradiation promotes cell proliferation and expression of anti-apoptosis proteins in Par-C10 cells, but it does not significantly affect amylase secretion and does not induce rapid cell death in isolated acinar cells from rat parotid glands.

  8. CFTR-Mediated Cl− Transport in the Acinar and Duct Cells of Rabbit Lacrimal Gland

    PubMed Central

    Lu, Michael; Ding, Chuanqing

    2013-01-01

    Purpose We investigated the role that the cystic fibrosis transmembrane conductance regulator (CFTR) may play in Cl− transport in the acinar and ductal epithelial cells of rabbit lacrimal gland (LG). Methods Primary cultured LG acinar cells were processed for whole-cell patch-clamp electrophysiological recording of Cl− currents by using perfusion media with high and low [Cl−], 10 μM forskolin and 100 μM 3-isobutyl-1-methylxanthine (IBMX), the non-specific Cl− channel blocker 4,4′-disothiocyanostilbene-2, 2′ sulphonic acid (DIDS; 100 μM) and CFTRinh-172 (10 μM), a specific blocker for CFTR. Ex vivo live cell imaging of [Cl−] changes in duct cells was performed on freshly dissected LG duct with a multiphoton confocal laser scanning microscope using a Cl− sensitive fluorescence dye, N-[ethoxycarbonylmethyl]-6-methoxy-quinolinium bromide. Results Whole-cell patch-clamp studies demonstrated the presence of Cl− current in isolated acinar cells and revealed that this Cl− current was mediated by CFTR channel. Live cell imaging also showed the presence of CFTR-mediated Cl− transport across the plasma membrane of duct cells. Conclusions Our previous data showed the presence of CFTR in all acinar and duct cells within the rabbit LG, with expression most prominent in the apical membranes of duct cells. The present study demonstrates that CFTR is actively involved in Cl− transport in both acinar cells and epithelial cells from duct segments, suggesting that CFTR may play a significant role in LG secretion. PMID:22578307

  9. Immunohistochemical localization of atrial natriuretic factor (ANF) in the excretory system of the rabbit parotid gland.

    PubMed

    Valentino, B; Farina Lipari, E; Carini, F; Valenza, V

    1999-01-01

    The immunohistochemical localization of atrial natriuretic factor (ANF) in the rabbit parotid gland was performed using an antibody against rabbit ANF and avidin-biotin or streptoavidin as detector. Results showed positivity in cuboidal and columnar cells of intralobular ducts and in basal cells of extralobular and main excretory duct. These data support the hypothesis that ANF produced by intralobular ducts could act through a paracrine mechanism; ANF produced by extralobular and main ducts may play a role in the regulation of salivary composition.

  10. DNA quantification as prognostic factor in a case of acinar cell carcinoma of the parotid gland, diagnosed by FNA.

    PubMed

    Azúa-Romeo, Javier; Sánchez-Garnica, Juan Carlos; Azúa-Blanco, Javier; Tovar-Lázaro, Mayte

    2005-01-01

    Hereby we present a case of a 43-years-old male who complained of a three years history preauricular painful mass. Fine needle aspiration cytology was performed, diagnosing of compatible with acinar cell carcinoma, thus DNA quantification by image cytometry was carried out. Biological parameters studied (ploidy, S-phase, 5-c exceeding rate) showed that it is a low grade of malignancy lesion. Total parotidectomy conservative of facial nerve was recommended, without regional lymphadenectomy. Patient remains, one year later, asymptomatic and free of disease.

  11. PP2C phosphatase activity is coupled to cAMP-mediated pathway in rat parotid acinar cells.

    PubMed

    Yokoyama, N; Kobayashi, T; Tamura, S; Sugiya, H

    1995-07-01

    A 26 kDa particulate protein is phosphorylated during stimulation of amylase secretion by a beta-adrenergic agonist in the rat parotid gland. Previous study has shown that PP2C phosphatase is involved in dephosphorylation of this 26 kDa protein [Yokoyama, N. et al. (1994) Biochem. Biophys. Res. Commun. 200, 497-503]. In this study, immunotransblot analysis using anti-PP2C phosphatase antibody showed that PP2C phosphatase was found prominently in the cystolic fractions and less in secretory granule membranes. When cells were stimulated by isoproterenol, cytosolic PP2C phosphatase activity increased to 145% at 5 min and returned to basal level at 30 min. Forskolin increased PP2C phosphatase activity. H89 inhibited increase of PP2C phosphatase activity following beta-adrenergic stimulation. These results suggest that PP2C phosphatase activity is regulated by cAMP-mediated signaling following beta-adrenergic stimulation and participates in dephosphorylation of this 26 kDa protein.

  12. Purification and characterization of protein phosphatase 2C in rat parotid acinar cells: two forms of Mg(2+)-activated histone phosphatase and phosphorylation by cAMP-dependent protein kinase.

    PubMed

    Yokoyama, N; Kobayashi, T; Tamura, S; Sugiya, H

    1996-07-01

    Two forms of Mg(2+)-activated histone phosphatase activities were partially purified from rat parotid acinar cells using Mono Q and gel filtration chromatography. Both enzymes activities were dependent on the presence of Mg2+, showing little activity in the presence of EDTA. The activities fractionated on the Mono Q column into two peaks: the first was a minor peak of histone phosphatase activity; the second was a major peak. These two peaks eluted at distinct positions on the gel filtration column. The molecular masses of the two peak fractions corresponded to 46 and 55 kDa, respectively on SDS-gels. The first 46-kDa peak immunoreacted with anti-PP2Calpha phosphatase antibody and like PP2Calpha phosphatase could be phosphorylated by cAMP-dependent protein kinase. The second 55-kDa peak showed neither reactivity with anti-PP2Calpha phosphatase antibody nor phosphorylability by cAMP-dependent protein kinase, but retained a Mg2+ or Mn2+ dependence for its histone phosphatase activity. Ca2+ showed a strong inhibition on this activity. On the basis of these observations, we have identified the first peak enzyme as PP2Calpha phosphatase and the second peak as a novel PP2C-like phosphatase.

  13. Telocytes in parotid glands.

    PubMed

    Nicolescu, Mihnea I; Bucur, Alexandru; Dinca, Octavian; Rusu, Mugurel C; Popescu, Laurentiu M

    2012-03-01

    The parotid histological structure includes acinar, ductal, and myoepithelial cells, surrounded by a connective stromal component. The parotid stroma is mostly regarded as an inert shell, consisting of septa, which divide the parenchyma. Telocytes were recently identified as a new stromal cell type in various organs, including exocrine pancreas. We aimed to evaluate telocytes presence in parotid stroma and whether their topographical features might support an involvement in parotid function modulation. Serial ultrathin sections of human and rat parotid glands were studied and compared by transmission electron microscopy. Two-dimensional concatenation of sequenced micrographs allowed the ultrastructural identification of parotid telocytes, with their specific long, thin, and moniliform prolongations (telopodes). Telocyte location appeared frequently as a strategic one, in close contact or vicinity of both secretory (acini and ducts) and regulatory (nerves and blood vessels) apparatuses. They were also found in the interacinar and the subductal stroma. Two previously reported telocyte markers (c-kit/CD117 and vimentin) were assayed by immunohistochemistry. Actin expression was also evaluated. Telocytes are making a network, especially by branching of their long telopodes. Elements of this telocyte network are interacting with each other (homocellular connections) as well as with other cell types (heterocellular connections). These interactions are achieved either by direct contact (stromal synapse), or mediated via shed microvesicles/exosomes. Since telocyte connections include both neurovascular and exocrine elements (e.g., acini and ducts), it is attractive to think that telocytes might mediate and integrate neural and/or vascular input with parotid function.

  14. Mechanisms Underlying Activation of α1-Adrenergic Receptor-Induced Trafficking of AQP5 in Rat Parotid Acinar Cells under Isotonic or Hypotonic Conditions

    PubMed Central

    Bragiel, Aneta M.; Wang, Di; Pieczonka, Tomasz D.; Shono, Masayuki; Ishikawa, Yasuko

    2016-01-01

    Defective cellular trafficking of aquaporin-5 (AQP5) to the apical plasma membrane (APM) in salivary glands is associated with the loss of salivary fluid secretion. To examine mechanisms of α1-adrenoceptor (AR)-induced trafficking of AQP5, immunoconfocal microscopy and Western blot analysis were used to analyze AQP5 localization in parotid tissues stimulated with phenylephrine under different osmolality. Phenylephrine-induced trafficking of AQP5 to the APM and lateral plasma membrane (LPM) was mediated via the α1A-AR subtype, but not the α1B- and α1D-AR subtypes. Phenylephrine-induced trafficking of AQP5 was inhibited by ODQ and KT5823, inhibitors of nitric oxide (NO)-stimulated guanylcyclase (GC) and protein kinase (PK) G, respectively, indicating the involvement of the NO/ soluble (c) GC/PKG signaling pathway. Under isotonic conditions, phenylephrine-induced trafficking was inhibited by La3+, implying the participation of store-operated Ca2+ channel. Under hypotonic conditions, phenylephrine-induced trafficking of AQP5 to the APM was higher than that under isotonic conditions. Under non-stimulated conditions, hypotonicity-induced trafficking of AQP5 to the APM was inhibited by ruthenium red and La3+, suggesting the involvement of extracellular Ca2+ entry. Thus, α1A-AR activation induced the trafficking of AQP5 to the APM and LPM via the Ca2+/ cyclic guanosine monophosphate (cGMP)/PKG signaling pathway, which is associated with store-operated Ca2+ entry. PMID:27367668

  15. [Sialoadenosis of the parotid glands: diagnostic considerations].

    PubMed

    Bagán Sebastián, J V; Silvestre Donat, F J

    1990-09-01

    We present 3 cases of Sialoadenosis of the parotid glands, one male and two females, who presented associated systemic pathology (liver cirrhosis and diabetes mellitus), detected following clinically suspect syaloadenosis (the patients were unaware of their systemic disease). In all three cases definitive diagnosis was established by needle aspiration of the gland. Which revealed great acinar dilatation. Finally, differential diagnosis was established between sialoadenosis and those conditions with clinical presentations similar to those described for sialoadenosis.

  16. Function of parotid gland following irradiation and its relation to biological parameters

    SciTech Connect

    Sasaki, T.; Yamamoto, M.; Takeda, M.

    1980-09-01

    The function of the parotid gland in the mouse (synthesis and secretion of ..cap alpha..-amylase) following X irradiation was analyzed in relation to the parameters of surviving acinar cell fraction, DNA or protein content, and wet weight of the gland. Both synthesis and secretion of amylase in parotid were essentially unchanged when mice were irradiated with a dose of up to 3000 rad. When mice were irradiated and then given a proliferative stimulus of isoproterenol, latent lethal damage in the acinar cell population was expressed and resulted in cell degeneration in a dose-dependent manner. The mean value of amylase activity per gland in similarly treated parotids was, however, totally unaffected. The relationship between amylase activity per gland and the other biological parameters was analyzed by regression analysis. The results indicate that amylase activity per surviving acinar cell increased proportionately to compensate for the loss of acinar cells.

  17. Ultrastructural studies of the parotid glands in sialadenosis.

    PubMed

    Donath, K; Seifert, G

    1975-01-01

    30 parotid biopsies of patients with sialadenosis--a symmetrical, painless, non-inflammatory, recurrent parotid swelling--were studied by electron microscopy. The patients suffered from different diseases, such as diabetes mellitus, liver diseases, hypertension and other affections. Parotid biopsies from 25 patients with slight parotitis or with oral cancer were used as controls. Morphometric studies reveal that the parotid swelling is caused by an enlargement of acinar cells. In controls the average diameters of the acinar cells are 30 to 40 mu. In sialadenosis the diameters are enlarged to 50 to 70 mu, in some cases to a maximum of 100 mu. Histologically the cytoplasm of the enlarged acinar cells shows either a granular pattern due to a numerical increase in secretory granules or a vacuolar transformation. Ultrastructurally the vacuolar transformed acinar cells also contain an increased number of granules with less electron density than the surrounding cytoplasm. Three types of sialadenosis can be distinguished with regard to the electron density of the acinar granules: a) a dark granular type, b) a pale granular type and c) a mixed granular type. The mixed granular type probably develops from the dark granular form. Alterations leading to the destruction of the myoepithelial cells were observed in all three types of sialadenosis with minimal changes in the dark granular type. Degenerative alterations of the autonomic nervous system are evident in all three groups with most pronounced changes in the pale granular type of sialadenosis. The ultrastructural alterations are interpreted as a disturbance of secretion, probably primarily caused by the degeneration of the autonomic nervous system. The alteration of the autonomic nervous system is suggested to be the common pathogenetic principle in all types of human sialadenosis occurring with different basic diseases. The enlargement of the acinar cells is the result of an intracellular disturbance in the secretory

  18. Effects of Benzodiazepines on Acinar and Myoepithelial Cells

    PubMed Central

    Mattioli, Tatiana M. F.; Alanis, Luciana R. A.; Sapelli, Silvana da Silva; de Lima, Antonio A. S.; de Noronha, Lucia; Rosa, Edvaldo A. R.; Althobaiti, Yusuf S.; Almalki, Atiah H.; Sari, Youssef; Ignacio, Sergio A.; Johann, Aline C. B. R.; Gregio, Ana M. T.

    2016-01-01

    Background: Benzodiazepines (BZDs), the most commonly prescribed psychotropic drugs with anxiolytic action, may cause hyposalivation. It has been previously shown that BZDs can cause hypertrophy and decrease the acini cell number. In this study, we investigated the effects of BZDs and pilocarpine on rat parotid glands, specifically on acinar, ductal, and myoepithelial cells. Methods: Ninety male Wistar rats were divided into nine groups. Control groups received a saline solution for 30 days (C30) and 60 days (C60), and pilocarpine (PILO) for 60 days. Experimental groups received lorazepam (L30) and midazolam (M30) for 30 days. Another group (LS60 or MS60) received lorazepam or midazolam for 30 days, respectively, and saline for additional 30 days. Finally, other groups (LP60 or MP60) received either lorazepam or midazolam for 30 days, respectively, and pilocarpine for additional 30 days. The expression of calponin in myoepithelial cells and the proliferating cell nuclear antigen (PCNA) in acinar and ductal cells were evaluated. Results: Animals treated with lorazepam showed an increase in the number of positive staining cells for calponin as compared to control animals (p < 0.05). Midazolam administered with pilocarpine (MP60) induced an increase in the proliferation of acinar and ductal cells and a decrease in the positive staining cells for calponin as compared to midazolam administered with saline (MS60). Conclusion: We found that myoepithelial cells might be more sensitive to the effects of BZD than acinar and ductal cells in rat parotid glands. PMID:27445812

  19. Transplantable pancreatic acinar carcinoma

    SciTech Connect

    Warren, J.R.; Reddy, J.K.

    1981-03-15

    Fragments of the nafenopin-induced pancreatic acinar cell carcinoma of rat have been examined in vitro for patterns of intracellular protein transport and carbamylcholine-induced protein discharge. Continuous incubation of the fragments with (3H)-leucine for 60 minutes resulted in labeling of rough endoplasmic reticulum, Golgi cisternae, and mature zymogen granules, revealed by electron microscope autoradiography. This result indicates transport of newly synthesized protein from the rough endoplasmic reticulum to mature zymogen granules in approximately 60 minutes. The secretagogue carbamylcholine induced the discharge of radioactive protein by carcinoma fragments pulse-chase labeled with (3H)-leucine. A maximal effective carbamylcholine concentration of 10(-5) M was determined. The acinar carcinoma resembles normal exocrine pancreas in the observed rate of intracellular protein transport and effective secretagogue concentration. However, the acinar carcinoma fragments demonstrated an apparent low rate of carbamylcholine-induced radioactive protein discharge as compared with normal pancreatic lobules or acinar cells. It is suggested that the apparent low rate of radioactive protein discharge reflects functional immaturity of the acinar carcinoma. Possible relationships of functional differentiation to the heterogeneous cytodifferentiation of the pancreatic acinar carcinoma are discussed.

  20. Parotid angiofibroma

    PubMed Central

    Hallur, Neelakamal H; Zainab, Heena; Shah, Ashwin; Siddiqua, Aaisha

    2014-01-01

    Angiofibromas are rare, benign, locally invasive vascular tumors, which represent 0.05-0.5% of all head and neck tumors. Most frequent site of occurrence is the posterior nasopharynx, called as nasopharyngeal angiofibromas (NA), when these arise outside the nasopharyngeal region they are termed as extranasopharyngeal angiofibromas (ENA). Only 65 cases of ENA have been reported, and the most common site has been reported to be maxilla followed by ethmoids. Other unusual sites of occurrence reported so far in literature are nasal cavity, nasal septum, larynx, sphenoid sinus, pterygomaxillary fissure, infratemporal fossa, cheek, oropharynx, retromolar area, middle turbinate, inferior turbinate, and tonsil. ENA arising from the superficial lobe of parotid gland has not been reported in the literature so far and this case is the first to be reported. PMID:25328316

  1. Primary retroperitoneal acinar cell cystadenoma.

    PubMed

    Pesci, Anna; Castelli, Paola; Facci, Enrico; Romano, Luigi; Zamboni, Giuseppe

    2012-03-01

    In this report, we describe a case of hitherto unreported primary retroperitoneal acinar cell cystadenoma that morphologically and immunophenotypically resembled pancreatic acinar cell cystadenoma. Pancreatic acinar cell cystadenoma is a very uncommon benign lesion characterized by acinar cell differentiation, the evidence of pancreatic exocrine enzyme production, and the absence of cellular atypia. Our case occurred in a 55-year-old woman presenting a 10-cm multilocular cystic lesion in the retroperitoneum thought to be a mucinous cystic neoplasm. At laparotomy, the cystic mass, which showed no connection with any organ, was completely resected with a clinical diagnosis of cystic lymphangioma. The diagnosis of retroperitoneal acinar cell cystadenoma was based on the recognition of morphological acinar differentiation, the immunohistochemical demonstration of the acinar marker trypsin, and the absence of cellular atypia. These peculiar features can be used in the differential diagnosis with all the other cystic lesions of the retroperitoneum.

  2. [Sialadenosis of the parotid gland after chronic nicotine use].

    PubMed

    Maier, H; Mall, G; Born, I A

    1991-04-01

    The effect of chronic nicotine consumption on the morphology of the rat parotid gland was investigated. After nicotine-loading for 90 days with an average serum nicotine concentration of 78 +/- 10 ng/ml a significant increase of acinar cell volume was observed. The acinar cells contained an increased number of enlarged light, immature secretory granules. These findings were confirmed by morphometric analysis. Further an increase of the granular endoplasmatic reticulum, an enlargement of the Golgi complexes and an oedematous swelling of intraglandular autonomous nerves were found. Similar findings have been observed in the parotid gland of animals and also of humans chronically treated with the beta-adrenergic drugs aludrin and isoproterenol, and have been termed "sialadenosis". It seems likely that the observed morphological alterations are caused by a stimulation of glandular beta-adrenoceptors via a nicotine-induced release of catecholamines from the adrenals.

  3. Rare Parotid Gland Diseases.

    PubMed

    Sanan, Akshay; Cognetti, David M

    2016-04-01

    The differential diagnosis for "rare" parotid gland diseases is broad and encompasses infectious, neoplastic, autoimmune, metabolic, and iatrogenic etiologies. The body of knowledge of parotid gland diseases has grown owing to advances in imaging and pathologic analysis and molecular technology. This article reviews rare parotid diseases, discussing the respective disease's clinical presentation, diagnosis, imaging, pathogenesis, treatment, and prognosis.

  4. Cell deletion by apoptosis during regression of rat parotid sialadenosis.

    PubMed

    Chisholm, D M; Adi, M M; Ervine, I M; Ogden, G R

    1995-01-01

    Enlargement of the rat parotid salivary glands was induced by repeated administration of isoproterenol. Mean wet weights of the treated glands increased steadily to 240% of control values. Following withdrawal of the drug, quantitative histological techniques were used to investigate the balance between hypertrophy, hyperplasia and apoptosis. The volume occupied by acinar cells relative to the total gland volume together with cytoplasmic magnitude of nuclear area ratios as measures of hypertrophy increased during the early experimental period. Similarly, serous acinar cell mitotic counts increased, indicating that hyperplasia had occurred. Apoptosis was demonstrated at light microscopical level to be the main mechanism for cell deletion as the glands returned to normal size and weight. The results indicate that hypertrophy and hyperplasia of serous acinar cells contribute to isoproterenol-induced sialadenosis. The experimental animal model demonstrates that these proliferative changes are completed by 48 h and thereafter are balanced by apoptosis as the glands recover their normal size and weight.

  5. Histological analysis of parotid and submandibular glands in chronic alcohol abuse: a necropsy study.

    PubMed

    Scott, J; Burns, J; Flower, E A

    1988-08-01

    A quantitative histological analysis of the major salivary glands was carried out at necropsy in 28 alcoholics and in a series of age and sex matched controls. The findings were related to the different types of histologically diagnosed liver disease present. Significant quantitative changes of salivary gland structure were noted in cirrhosis but not in other forms of alcoholic liver disease. In cirrhotic subjects the parotid contained proportionally more adipose but less acinar tissues than in controls. The submandibular gland showed a proportional increase in adiposity and reduction in fibrovascular tissues but no noticeable reduction in its acinar proportional volume. Neither grossly detectable parotid enlargement nor acinar hypertrophy, a feature which has previously been noted as characteristic of alcoholic sialadenosis, were evident in this series. These findings provide little structural support for the reportedly increased secretory capacity of salivary glands in chronic alcohol abuse.

  6. Histological analysis of parotid and submandibular glands in chronic alcohol abuse: a necropsy study.

    PubMed Central

    Scott, J; Burns, J; Flower, E A

    1988-01-01

    A quantitative histological analysis of the major salivary glands was carried out at necropsy in 28 alcoholics and in a series of age and sex matched controls. The findings were related to the different types of histologically diagnosed liver disease present. Significant quantitative changes of salivary gland structure were noted in cirrhosis but not in other forms of alcoholic liver disease. In cirrhotic subjects the parotid contained proportionally more adipose but less acinar tissues than in controls. The submandibular gland showed a proportional increase in adiposity and reduction in fibrovascular tissues but no noticeable reduction in its acinar proportional volume. Neither grossly detectable parotid enlargement nor acinar hypertrophy, a feature which has previously been noted as characteristic of alcoholic sialadenosis, were evident in this series. These findings provide little structural support for the reportedly increased secretory capacity of salivary glands in chronic alcohol abuse. PMID:3170770

  7. Rat parotid cell function in vitro following x irradiation in vivo

    SciTech Connect

    Bodner, L.; Kuyatt, B.L.; Hand, A.R.; Baum, B.J.

    1984-02-01

    The effect of X irradiation on rat parotid acinar cell function was evaluated in vitro 1, 3, and 7 days following in vivo exposure to 2000 R. Several cellular functions were followed: protein secretion (amylase release), ion movement (K/sup +/ efflux and reuptake), amino acid transport (..cap alpha..-amino(/sup 14/C)isobutyric acid), and an intermediary metabolic response ((/sup 14/C)glucose oxidation). In addition both the morphologic appearance and in vivo saliva secretory ability of parotid cells were assessed. Our results demonstrate that surviving rat parotid acinar cells, isolated and studied in vitro 1-7 days following 2000 R, remain functionally intact despite in vivo diminution of secretory function.

  8. Parotid Gland Imaging.

    PubMed

    Prasad, Ravi S

    2016-04-01

    In this article, various imaging modalities are discussed for evaluation of parotid disease, from congenital to inflammatory to neoplastic etiologies. Key imaging characteristics are outlined using case examples. Introduction to biological imaging is highlighted. Additionally, image-guided biopsy techniques are illustrated for sampling parotid and parapharyngeal space lesions in a minimally invasive manner.

  9. [Sialadenosis of the parotid gland. Ultrastructural, clinical and experimental findings in disturbances of secretion (author's transl)].

    PubMed

    Donath, K

    1976-01-01

    Among the secretory disturbances ("Dyschylien") of salivary glands the sialadenosis of the parotid gland is a clinic and a morphologic definited entity. The typical clinical symptom is a bilateral, often recurrent, and painless swelling of the parotid gland. The characteristic pathological findings consist in an acinar cell hypertrophy without any inflammatory signs. According to this definition, sialadenosis has to be separated from those diseases of salivary glands, which are primarily altered by inflammation of the salivary tissue with secondary secretory disturbances. From flinical point of view it is possible to distinguish the following kinds of sialadenosis according to the syntropy with various diseases: Endocrine sialadenosis (in diabetes mellitus, dysfunction of gonads, pituitary gland, thyroid gland etc.); dystrophic-metabolic sialadenosis (malnutrition, avitaminosis, alcohilsm, chronic liver diseases etc.), and neurogenic sialadenosis (dysfunction of the vegetative nervous system, drug damages e.g. antihypertensive agents). The question arises, whether all forms of sialadenosis have a common etiology and a coincidental pathogenic factor. The following studies were carried out with the aim to find further details concerning the etiology and pathogenesis of sialadenosis. The study is based on the following material: a) 126 Biopsies of parotid glands from patients with sialadenosis (Register of salivary gland diseases at the Institute of Pathology, University of Hamburg, supported by Deutsche Forschungsgemeinschaft). This material was collected from 1965 to 1973. b) 80 Biopsies of parotid glands from patients with other diseases (parotitis [4]; acinic cell carcinoma [4]; other parotid and oral tumors [72]; for comparison. c) Experimental studies on the parotid salivary glands of Wistar-rats. The biopsies of the parotid glands were studied histologically, morphometrically, and ultrastructurally. The investigations centered on the ultrastruct of sialadenosis

  10. Controversies in Parotid Defect Reconstruction.

    PubMed

    Tamplen, Matthew; Knott, P Daniel; Fritz, Michael A; Seth, Rahul

    2016-08-01

    Reconstruction of the parotid defect is a complex topic that encompasses restoration of both facial form and function. The reconstructive surgeon must consider facial contour, avoidance of Frey syndrome, skin coverage, tumor surveillance, potential adjuvant therapy, and facial reanimation when addressing parotid defects. With each defect there are several options within the reconstructive ladder, creating controversies regarding optimal management. This article describes surgical approaches to reconstruction of parotid defects, highlighting areas of controversy.

  11. Alcoholic parotid sialadenosis.

    PubMed

    Mandel, L; Hamele-Bena, D

    1997-10-01

    Alcoholism is a primary cause of sialadenosis, which is an asymptomatic, bilateral enlargement of the parotid glands. The authors outline the pathogenesis, symptoms and testing involved in diagnosing sialadenosis. Recognizing sialadenosis is important because it may point to the unsuspected presence of underlying systemic disease. Therefore, dental practitioners need to be able to differentiate sialadenosis from an inflammatory or neoplastic process to prevent unnecessary treatment.

  12. Effect of low-level laser therapy on irradiated parotid glands—study in mice

    NASA Astrophysics Data System (ADS)

    Acauan, Monique Dossena; Gomes, Ana Paula Neutziling; Braga-Filho, Aroldo; de Figueiredo, Maria Antonia Zancanaro; Cherubini, Karen; Salum, Fernanda Gonçalves

    2015-10-01

    The objective of this study was to evaluate the effect of low-level laser therapy (LLLT) on radiotherapy-induced morphological changes and caspase-3 immunodetection in parotids of mice. Forty-one Swiss mice were divided into control, radiotherapy, 2- and 4-J laser groups. The experimental groups were exposed to ionizing radiation in a single session of 10 Gy. In the laser groups, a GaAlAs laser (830 nm, 100 mW, 0.028 cm2, 3.57 W/cm2) was used on the region corresponding to the parotid glands, with 2-J energy (20 s, 71 J/cm2) or 4 J (40 s, 135 J/cm2) per point. LLLT was performed immediately before and 24 h after radiotherapy. One point was applied in each parotid gland. The animals were euthanized 48 h or 7 days after radiotherapy and parotid glands were dissected for morphological analysis and immunodetection of caspase-3. There was no significant difference between groups in the immunodetection of caspase-3, but the laser groups had a lower percentage compared to the radiotherapy group. LLLT promoted the preservation of acinar structure, reduced the occurrence of vacuolation, and stimulated parotid gland vascularization. Of the two LLLT protocols, the one using 4 J of energy showed better results.

  13. Effect of low-level laser therapy on irradiated parotid glands--study in mice.

    PubMed

    Acauan, Monique Dossena; Gomes, Ana Paula Neutziling; Braga-Filho, Aroldo; de Figueiredo, Maria Antonia Zancanaro; Cherubini, Karen; Salum, Fernanda Gonçalves

    2015-10-01

    The objective of this study was to evaluate the effect of low-level laser therapy (LLLT) on radiotherapy-induced morphological changes and caspase-3 immunodetection in parotids of mice. Forty-one Swiss mice were divided into control, radiotherapy, 2- and 4-J laser groups. The experimental groups were exposed to ionizing radiation in a single session of 10 Gy. In the laser groups, a GaAlAs laser (830 nm, 100 mW, 0.028  cm2, 3.57  W/cm2) was used on the region corresponding to the parotid glands, with 2-J energy (20 s, 71  J/cm2) or 4 J (40 s, 135  J/cm2) per point. LLLT was performed immediately before and 24 h after radiotherapy. One point was applied in each parotid gland. The animals were euthanized 48 h or 7 days after radiotherapy and parotid glands were dissected for morphological analysis and immunodetection of caspase-3. There was no significant difference between groups in the immunodetection of caspase-3, but the laser groups had a lower percentage compared to the radiotherapy group. LLLT promoted the preservation of acinar structure, reduced the occurrence of vacuolation, and stimulated parotid gland vascularization. Of the two LLLT protocols, the one using 4 J of energy showed better results.

  14. [Epidemic parotiditis, a reportable disease].

    PubMed

    Boverhoff, J C; Baart, J A

    2013-01-01

    Three consecutive patients with an acute swelling of one of the cheeks, were diagnosed with epidemic parotiditis. The first phase of the diagnostic procedure for an acute cheek swelling is to eliminate the possibility of odontogenic causes. When odontogenic problems have been excluded, non-dentition-related causes may be considered. An acute, progressive swelling in the preauricular area can often be attributed to an inflammation of the parotid gland, but epidemic parotiditis should also be considered. Epidemic parotiditis, or mumps, is caused by the mumps virus. Contamination occurs aerogenically. In the Netherlands, mumps vaccine is an ingredient of the governmental combined mump-measles-rubella inoculation programme. However, in recent years several small-scale parotiditis epidemics have broken out, predominantly among young, inoculated adults. Oropharyngeal mucus and blood samples are needed to diagnose the disease. Each case of the disease should be reported to the community healthcare service.

  15. Further evidence for AQP8 expression in the myoepithelium of rat submandibular and parotid glands.

    PubMed

    Wellner, Robert B; Redman, Robert S; Swaim, William D; Baum, Bruce J

    2006-02-01

    Previously (Wellner et al., Pflugers Arch 441:49-56, 2000) we suggested that the localization of the aquaporins (AQPs) AQP5 and AQP8 in the apical and basolateral membranes of rat submandibular gland (SMG) acinar cells, respectively, provides for transcellular water flow during saliva formation. While the localization of AQP5 in this gland has been verified in several laboratories, there have been differing reports regarding AQP8 localization. Other investigators subsequently reported that AQP8 is not expressed in the acinar or ductal cells of the major salivary glands of the rat, but in the myoepithelium of each gland. Thus, we have carried out additional studies: (1) to reassess the localization of AQP8 in the rat SMG and (2) to assess the localization of AQP8 in the rat parotid gland (PG). Initially, we compared the localizations of AQP8 with recognized basolateral markers in acinar cells [the Na+,K+-ATPase and the Na+-K+-2Cl- cotransporter (NKCC1)]. Our results indicated that Na+,K+-ATPase localized in both the basal and lateral membranes of rat SMG acinar cells, whereas AQP8 was detected only in the basal regions of the acini. In the rat PG, AQP8 was invested near intercalated ducts and adjacent acini, whereas NKCC1 localized in the basolateral membranes of acinar cells. As these results were suggestive of myoepithelial localization in both glands, we compared AQP8 localization with the localization of smooth muscle actin, a myoepithelial marker. We found that AQP8 and smooth muscle actin colocalized in both the rat SMG and PG, providing additional strong support for a myoepithelial localization of AQP8. Thus, in agreement with an earlier report by other investigators (Elkjaer et al., Am J Physiol Renal Physiol 281:F1047-F1057, 2001), we report that AQP8 is expressed in the myoepithelial cells, but not in the acinar cells, of both the rat SMG and PG.

  16. Fine structure of the parotid gland in tree shrew (Tupaia glis).

    PubMed

    Suzuki, S; Mifune, H; Nishida, T; Obara, T; Kamimura, R; Sakamoto, H; Mohammad Abdul, A; Nishinakagawa, H

    1995-10-01

    The parotid glands of Tupaia glis were examined by light and transmission electron microscopy. The acinar cells were seromucous in nature, and contained many acidophilic granules with strong affinity for periodic acid-Schiff (PAS) and weak affinity for alcian blue (AB). These granules consisted of a fine granular matrix of moderate density in which a denser corpuscles or semilunar materials were present. Intercalated duct cells had a few fine vesicles, vacuoles and very few dense granules in the apical region. In occasional epithelial cells, acidophilic, PAS-positive and AB-negative bodies with moderate density were observed in the supranuclear region. The striated ducts consisted of columnar light and dark cells containing round or small ovoid granules of moderate density and did not show the granular duct as seen in the parotid glands of kobe mole and tenrec which are placed in the order insectivora.

  17. The ryanodine receptor is expressed in human pancreatic acinar cells and contributes to acinar cell injury.

    PubMed

    Lewarchik, Christopher M; Orabi, Abrahim I; Jin, Shunqian; Wang, Dong; Muili, Kamaldeen A; Shah, Ahsan U; Eisses, John F; Malik, Adeel; Bottino, Rita; Jayaraman, Thottala; Husain, Sohail Z

    2014-09-01

    Physiological calcium (Ca(2+)) signals within the pancreatic acinar cell regulate enzyme secretion, whereas aberrant Ca(2+) signals are associated with acinar cell injury. We have previously identified the ryanodine receptor (RyR), a Ca(2+) release channel on the endoplasmic reticulum, as a modulator of these pathological signals. In the present study, we establish that the RyR is expressed in human acinar cells and mediates acinar cell injury. We obtained pancreatic tissue from cadaveric donors and identified isoforms of RyR1 and RyR2 by qPCR. Immunofluorescence staining of the pancreas showed that the RyR is localized to the basal region of the acinar cell. Furthermore, the presence of RyR was confirmed from isolated human acinar cells by tritiated ryanodine binding. To determine whether the RyR is functionally active, mouse or human acinar cells were loaded with the high-affinity Ca(2+) dye (Fluo-4 AM) and stimulated with taurolithocholic acid 3-sulfate (TLCS) (500 μM) or carbachol (1 mM). Ryanodine (100 μM) pretreatment reduced the magnitude of the Ca(2+) signal and the area under the curve. To determine the effect of RyR blockade on injury, human acinar cells were stimulated with pathological stimuli, the bile acid TLCS (500 μM) or the muscarinic agonist carbachol (1 mM) in the presence or absence of the RyR inhibitor ryanodine. Ryanodine (100 μM) caused an 81% and 47% reduction in acinar cell injury, respectively, as measured by lactate dehydrogenase leakage (P < 0.05). Taken together, these data establish that the RyR is expressed in human acinar cells and that it modulates acinar Ca(2+) signals and cell injury.

  18. Radial transport along the human acinar tree.

    PubMed

    Henry, F S; Tsuda, A

    2010-10-01

    A numerical model of an expanding asymmetric alveolated duct was developed and used to investigate lateral transport between the central acinar channel and the surrounding alveoli along the acinar tree. Our results indicate that some degree of recirculation occurs in all but the terminal generations. We found that the rate of diffusional transport of axial momentum from the duct to the alveolus was by far the largest contributor to the resulting momentum in the alveolar flow but that the magnitude of the axial momentum is critical in determining the nature of the flow in the alveolus. Further, we found that alveolar flow rotation, and by implication chaotic mixing, is strongest in the entrance generations. We also found that the expanding alveolus provides a pathway by which particles with little intrinsic motion can enter the alveoli. Thus, our results offer a possible explanation for why submicron particles deposit preferentially in the acinar-entrance region.

  19. RADIAL TRANSPORT ALONG THE HUMAN ACINAR TREE

    PubMed Central

    Henry, F.S.; Tsuda, A.

    2013-01-01

    A numerical model of an expanding asymmetric alveolated duct was developed and used to investigate lateral transport between the central acinar channel and the surrounding alveoli along the acinar tree. Our results indicate that some degree of recirculation occurs in all but the terminal generations. We found that the rate of diffusional transport of axial momentum, from the duct to the alveolus, was by far the largest contributor to the resulting momentum in the alveolar flow but that the magnitude of the axial momentum is critical in determining the nature of the flow in the alveolus. Further, we found that alveolar flow rotation, and by implication chaotic mixing, are strongest in the entrance generations. We also found that the expanding alveolus provides a pathway by which particles with little intrinsic motion can enter the alveoli. Thus, our results offer a possible explanation for why submicron particles deposit preferentially in acinar entrance region. PMID:20887011

  20. Binding sites of Ulex europaeus-lectin I in human parotid gland. A light-microscopic and ultrastructural study using the immunoperoxidase technique and immunocryoultramicrotomy.

    PubMed

    Born, I A; Zimmer, K P; Schwechheimer, K; Maier, H; Möller, P

    1987-05-01

    Twenty non-neoplastic parotid glands (removed during neck dissection for regional tumours) were examined for cellular and subcellular binding sites of Ulex europaeus-lectin I (UEA-I), a lectin reported to be specific for alpha-L-fucose. For light microscopy, an extended peroxidase-antiperoxidase method was applied; for the evaluation of the subcellular localization of bound lectin, three of these glands were examined following immunocryoultramicrotomy and staining by the protein A-gold technique. In addition to the known cytoplasmic affinity of UEA-I for capillary endothelium, acinar cells bound the lectin within the cytoplasmic compartment; the number and distribution of stained acinar cells varied among individuals. Furthermore, cytomembrane-bound labelling that occurred most markedly at the luminar surface was observed in striated-duct epithelium. Using the electron microscope, protein A-gold particles were seen in zymogen granules and in Golgi cisternae of serous acinar cells; primary saliva secreted in the lumina exhibited strong labelling; serous acinar cells had binding sites on their cell membranes, striated-duct epithelium had binding sites on its surface membrane and in the vicinity of apical vesicles. Our results show that UEA-I is a useful tool for the study of the structure and functional states of the parotid gland epithelium and its associated pathological alterations.

  1. K+ transport and membrane potentials in isolated rat parotid acini

    SciTech Connect

    Nauntofte, B.; Dissing, S.

    1988-10-01

    42K+ transport properties of isolated rat parotid acini were characterized concomitant with measurements of membrane potentials (Em) by means of the fluorescent dye diSC3-(5). In unstimulated acini suspended in a 5 mM K+ buffer, Em was governed by the K+ and Cl- gradients and amounted to about -59 mV, a value that remained unaffected on cholinergic stimulation. In unstimulated acini, 42K+ influx was largely mediated by the Na+-K+ pump, and the residual influxes were mediated by a bumetanide-sensitive component (cotransport system) and by K+ channels. Efflux of 42K+ was largely mediated by a bumetanide-sensitive component and by K+ channels. In the unstimulated state, the cotransport system was mediating K+-K+ exchange without contributing to the net uptake of K+. Within 10 s after stimulation, a approximately 10-fold increase in the acinar K+ conductance (gK) occurred, resulting in a rapid net efflux of K+ that amounted to approximately 3.8 mmol.l cells-1.s-1. Measurements of 42K+ fluxes as a function of the external K+ concentration revealed that in the stimulated state gK increases when external K+ is raised from 0.7 to 10 mM, consistent with an activation of acinar gK by the binding of external K+ to the channel. 42K+ flux ratios as well as the effect of the K+ channel inhibitor from scorpion venom (LQV) suggest that approximately 90% of K+ transport in the stimulated state is mediated by ''maxi'' K+ channels.

  2. Microliths in the parotid of ferret investigated by electron microscopy and microanalysis

    PubMed Central

    Triantafyllou, Asterios; Harrison, John D; Garrett, John R

    2009-01-01

    The present investigation is an attempt to determine the occurrence, elemental composition and formation of microliths in the parotid of ferret. Parotids from four normal ferrets were examined by electron microscopy and X-ray microanalysis. Crystalline microliths were found in phagosomes of acinar cells, which occasionally contained secretory material, and in phagosomes situated between mitochondria of striated ductal cells. Crystalline microliths and microliths that consisted of granular material either without crystals or mixed with a component of crystals were found in lumina, where they were often associated with cellular debris. The crystals contained calcium and phosphorus. Phagy and stagnation related to pockets of inefficient secretory activity have been previously found to be features of the parotid of ferret. Thus, possibly persistent degradation of redundant cellular material, particularly secretory granules, in phagosomes results in accumulation of calcium and leads to calcified microliths, whereas consolidation of stagnant debris extracellularly does not involve such accumulation and leads to non-calcified or mixed microliths. PMID:19659902

  3. Sialadenosis of the salivary glands of the head. Studies on the physiology and pathophysiology of parotid secretion.

    PubMed

    Chilla, R

    1981-01-01

    Sialadenosis is a noninflammatory disease of the salivary glands of the head. It is observed in connection with endocrine disorders, malnutrition and neurologic diseases. The parotid glands are predominantly affected by a parenchymatous swelling. Based on morphologic and biochemical investigations it can be assumed that disorders of the gland's acinar protein secretion are responsible for sialadenosis. Changes in secretory behavior are caused by either excessive stimulation ('stimulatory proteodyschylia') or by inhibition of secretion ('inhibitory proteodyschylia'). The origin of these secretory disorders is very likely to be found in the vegetative nerve system. The pathophysiology of sialadenosis can therefore only be understood after elucidation of the physiologic mechanisms of salivary gland secretion. Research in the field of biophysical and biochemical principles underlying parotid secretion has made considerable progress in recent years. A comprehensive review of this new evidence is necessary for the understanding of experimental studies on the pathogenesis of sialadenosis.

  4. Unique cellular structures in the parotid gland of an Old world fruit bat, Pteropus lylei (Lyle's flying fox).

    PubMed

    Lanlua, Passara; Sricharoenvej, Sirinush; Niyomchan, Apichaya; Chico, Diane E

    2007-01-01

    Pteropus lylei (Lyle's flying fox), an Old World fruit bat, consumes only ripe fruit, which contains low protein and sodium. The carpophagous diet of P. lylei presents an adaptive challenge for salivary glands to conserve sufficient nutrition for living. Therefore, the parotid glands in both sexes were investigated by using light microscopy and transmission electron microscopy. No structural difference was observed in the parotid glands between sexes. The acinar cell contained dense serous secretory granules, prominent luminal microvilli and intercellular canaliculi. The intercalated duct exhibited simple cuboidal epithelium with no secretory granule. Striated duct consisted of simple columnar epithelium with basal striation, numerous elongated mitochondria, and apical vesicles. In the interlobular duct, simple tall columnar epithelium and apocrine secretion were found. The interlobar and excretory ducts surprisingly contained continuous capillaries that intervened in stratified cuboidal epithelium. In addition, there were several blood vessels around the interlobular, interlobar and excretory ducts. The morphological adaptation of the parotid gland observed in P. lylei enables this species to obtain sufficient nutrients from the preferred consumption of ripe fruit. Serous secretory granule was suitable for digestion of ripe fruit. A well-developed striated duct, continuous capillaries among the epithelial cells of interlobar and excretory ducts, and numerous blood vessels around these ducts enhanced the reabsorption of amino acids and ions. Structural variations in the parotid gland can indicate not only a correlation to diet and survival but also a close relationship of the Old World fruit bat to other kinds of bats.

  5. Practical imaging of the parotid gland.

    PubMed

    Bag, Asim K; Curé, Joel K; Chapman, Philip R; Pettibon, Keith D; Gaddamanugu, Siddhartha

    2015-01-01

    The parotid gland may be affected by numerous pathologies, and physicians from many different medical and surgical specialties request parotid imaging. Mastering the typical imaging features of various types of parotid pathology is facilitated by understanding how various diseases produce their characteristic imaging findings. In this review article, we present succinct overviews of the normal anatomy and the common pathologies of the parotid gland and recommend a practical approach to differential diagnosis that can be easily implemented in day-to-day radiology practice.

  6. Choroid plexus acinar adenoma: a case report.

    PubMed

    Rembao-Bojórquez, Daniel; Vega, Rosalba; Bermúdez-Maldonado, Luis; Gutiérrez, Ramón; Salinas, Citlaltepetl; Tena-Suck, Martha

    2007-06-01

    Mucus-secreting adenomas or acinar adenoma of the choroid plexus are very rare. We report the case of a 79-year-old male with a 3-year history of occipital headaches with vomiting, ataxia and cerebellar signs. He was first seen due to difficulty while walking. He was admitted to the hospital with significant tumor expansion and clinical deterioration. CT and MRI revealed obstructive hydrocephalus secondary to a large fourth ventricular cyst mass, which enhanced markedly on contrast administration. Pathological findings were consistent with an acinar choroid plexus adenoma. The tumor was attached to the ependymal lining and was strongly adhered to the walls and floor of the IV ventricle. Post-operative bleeding complicated partial removal of this tumor. The patient died 6 h after surgery.

  7. An introduction to acinar pressures in BPH and prostate cancer.

    PubMed

    Wadhera, Panikar

    2013-06-01

    Intra-acinar and peri-acinar pressures in the prostate might be key factors in the evolution of its zonal morphology and the pathogenesis of BPH and cancer. Herein, I hypothesize that intra-acinar pressures lead to a decrease in apoptosis by distending or stretching acinar epithelium and its surrounding stroma. Increased prostatic smooth muscle content and tone might generate peri-acinar pressures, which could, in the long-term, counteract intra-acinar pressures and decrease epithelial stretch. Thus, it is proposed that BPH (characterized by increased prostatic smooth muscle and, therefore, raised peri-acinar pressures) might decrease the risk of prostate cancer progression by counteracting intra-acinar pressures. In the context of this theory, the transition zone might have evolved as a specialized region within the prostate that can mount a concerted stromal-epithelial response to increased urethral and intra-acinar pressures (BPH), and the urethral angulation, anterior stroma and the prostatic capsule have an adjunctive evolutionary role in this phenomenon.

  8. Bilateral parotid swelling: a radiological review

    PubMed Central

    Gadodia, A; Bhalla, A S; Sharma, R; Thakar, A; Parshad, R

    2011-01-01

    Bilateral parotid swelling is not an uncommon occurrence and may pose a challenge for clinicians and radiologists. Numerous causes of bilateral parotid swellings have been identified. The purpose of this pictorial review is to display this wide array with a focus on multimodality approach. PMID:21960397

  9. Case report. Acinar cell carcinoma with fatty change arising from the pancreas.

    PubMed

    Chung, W-S; Park, M-S; Kim, D W; Kim, K W

    2011-12-01

    Acinar cell carcinoma of the pancreas is a rare malignant tumour developing from acinar cells, accounting for approximately 1% of pancreatic exocrine tumours. We experienced a case of an acinar cell carcinoma with fatty change. To the best of our knowledge, this is the first case report of an acinar cell carcinoma with fatty change in the clinical literature.

  10. Treatment of complications of parotid gland surgery

    PubMed Central

    Marchese-Ragona, R; De Filippis, C; Marioni, G; Staffieri, A

    2005-01-01

    Summary Although several reports in the literature have documented the surgical technique, and the oncological outcome achieved with parotidectomy, only a few articles have described the complications of parotid gland surgery and their management. Several complications have been reported in parotid surgery. We re-classified the complications of parotidectomy in intra-operative and post-operative (early and late). The commonest complications after parotidectomy are temporary or permanent facial palsy and Frey’s syndrome. PMID:16450773

  11. Giant Pleomorphic Adenoma of the Parotid Gland.

    PubMed

    Sajid, Muhammad; Rehman, Sajid; Misbah, Junaid

    2015-10-01

    Salivary gland tumours are a relatively rare entity. Pleomorphic adenoma is the most common amongst these, comprising 60 - 70% of all parotid tumours. Pleomorphic adenomas are benign and tend to increase in size slowly. Here we are presenting a case of giant pleomorphic adenoma of the parotid, being the largest in size to be excised in Pakistan in recorded literature measuring 24 x 22 x 12 cm and weighing 1.8 kgs. Superficial parotidectomy was done with an excellent cosmetic outcome.

  12. Infantile Hemangioendothelioma of the Parotid Gland

    PubMed Central

    Chaubal, Rajas; Tavri, Om; Sawant, Atul; Singh, Chitrangada

    2017-01-01

    A 4-month-old infant presented with a painless swelling overlying the left angle of mandible. Ultrasound and magnetic resonance imaging (MRI) revealed a large lesion replacing the entire left parotid gland, with multiple enlarged vessels. Homogeneous enhancement of the lesion was seen on the postcontrast MRI scans. Based on the imaging features, a diagnosis of infantile hemangioendothelioma of the parotid gland was offered. This helped in avoiding any further invasive testing. PMID:28217408

  13. TGF-β1 promotes acinar to ductal metaplasia of human pancreatic acinar cells

    PubMed Central

    Liu, Jun; Akanuma, Naoki; Liu, Chengyang; Naji, Ali; Halff, Glenn A.; Washburn, William K.; Sun, Luzhe; Wang, Pei

    2016-01-01

    Animal studies suggest that pancreatitis-induced acinar-to-ductal metaplasia (ADM) is a key event for pancreatic ductal adenocarcinoma (PDAC) initiation. However, there has not been an adequate system to explore the mechanisms of human ADM induction. We have developed a flow cytometry-based, high resolution lineage tracing method and 3D culture system to analyse ADM in human cells. In this system, well-known mouse ADM inducers did not promote ADM in human cells. In contrast, TGF-β1 efficiently converted human acinar cells to duct-like cells (AD) in a SMAD-dependent manner, highlighting fundamental differences between the species. Functionally, AD cells gained transient proliferative capacity. Furthermore, oncogenic KRAS did not induce acinar cell proliferation, but did sustain the proliferation of AD cells, suggesting that oncogenic KRAS requires ADM-associated-changes to promote PDAC initiation. This ADM model provides a novel platform to explore the mechanisms involved in the development of human pancreatic diseases. PMID:27485764

  14. Transcutaneous approach for the removal of parotid gland stones.

    PubMed

    Oh, Hee-Kyun; Park, Hong-Ju; Oh, Je-Seok; Jung, Seunggon; Kook, Min-Suk

    2014-11-01

    Salivary stones in the parotid gland can be treated with a wide range of methods. Stones close to the opening of the duct can be easily removed through the oral cavity, whereas the entire salivary gland may need to be removed if stones are located close to the parotid gland. In such cases, surgical removal of the parotid gland may be lengthy and may produce facial nerve injury. We report a simple extraoral approach used for the removal of parotid gland stones located close to the parotid gland by precisely identifying the location of stones in 2 patients with parotid sialolithiasis.

  15. THE LIPID CONSTITUENTS OF WHOLE AND PAROTID SALIVA

    DTIC Science & Technology

    Chloroform: methanol extracts of whole and parotid saliva were subjected to paper chromatography to further characterize their lipid components. The...the sample materials. Whole and parotid saliva had similar nonphosphatides, but differed in their phospholipid composition. (Author)

  16. The role of anisotropic expansion for pulmonary acinar aerosol deposition

    PubMed Central

    Hofemeier, Philipp; Sznitman, Josué

    2016-01-01

    Lung deformations at the local pulmonary acinar scale are intrinsically anisotropic. Despite progress in imaging modalities, the true heterogeneous nature of acinar expansion during breathing remains controversial, where our understanding of inhaled aerosol deposition still widely emanates from studies under self-similar, isotropic wall motions. Building on recent 3D models of multi-generation acinar networks, we explore in numerical simulations how different hypothesized scenarios of anisotropic expansion influence deposition outcomes of inhaled aerosols in the acinar depths. While the broader range of particles acknowledged to reach the acinar region (dp = 0.005–5.0 μm) are largely unaffected by the details of anisotropic expansion under tidal breathing, our results suggest nevertheless that anisotropy modulates the deposition sites and fractions for a narrow band of sub-micron particles (dp ~ 0.5–0.75 μm), where the fate of aerosols is greatly intertwined with local convective flows. Our findings underscore how intrinsic aerosol motion (i.e. diffusion, sedimentation) undermines the role of anisotropic wall expansion that is often attributed in determining aerosol mixing and acinar deposition. PMID:27614613

  17. A rare case of parotid gland lipoma arising from the deep lobe of the parotid gland

    PubMed Central

    Paparo, Francesco; Massarelli, Mauro; Giuliani, Giorgio

    2016-01-01

    Lipomas are the most commonly encountered benign mesenchymal tumors, but their occurrence in the head and neck is rare, even more at the level of the parotid region where they can be found nearby the parotid capsule, inside the capsule, or within the gland. In addition, lipomas involving the deep parotid lobe are extremely unusual. That is why lipomas are not often considered for differential diagnosis of parotid lumps. Concerning diagnostic tools, magnetic resonance imaging (MRI) is nowadays considered as the main imaging examination for parotid lipomas due to a characteristic signal intensity on T1- and T2-weighted images. Furthermore, even if the cost of MRI is nearly three times that of computed tomography, MRI is accurate, safe, and has few biological costs for the patient. In this reported case, MRI provided all information for either diagnosis or preoperative planning being the best diagnostic tool regarding tumor margin characteristics and surrounding tissues’ involvement. Concerning treatment, surgical excision of parotid masses is always mandatory for definitive diagnosis, but it is challenging because of the facial nerve. For this reason, a well-established surgical technique is mandatory for success. The authors present a rare case of parotid gland lipoma arising from the deep lobe and discuss diagnostic tools and surgical technique.

  18. Parotid lymphangioma associated with facial nerve paralysis.

    PubMed

    Imaizumi, Mitsuyoshi; Tani, Akiko; Ogawa, Hiroshi; Omori, Koichi

    2014-10-01

    Parotid lymphangioma is a relatively rare disease that is usually detected in infancy or early childhood, and which has typical features. Clinical reports of facial nerve paralysis caused by lymphangioma, however, are very rare. Usually, facial nerve paralysis in a child suggests malignancy. Here we report a very rare case of parotid lymphangioma associated with facial nerve paralysis. A 7-year-old boy was admitted to hospital with a rapidly enlarging mass in the left parotid region. Left peripheral-type facial nerve paralysis was also noted. Computed tomography and magnetic resonance imaging also revealed multiple cystic lesions. Open biopsy was undertaken in order to investigate the cause of the facial nerve paralysis. The histopathological findings of the excised tumor were consistent with lymphangioma. Prednisone (40 mg/day) was given in a tapering dose schedule. Facial nerve paralysis was completely cured 1 month after treatment. There has been no recurrent facial nerve paralysis for eight years.

  19. Therapeutic potential of targeting acinar cell reprogramming in pancreatic cancer.

    PubMed

    Wong, Chi-Hin; Li, You-Jia; Chen, Yang-Chao

    2016-08-21

    Pancreatic ductal adenocarcinoma (PDAC) is a common pancreatic cancer and the fourth leading cause of cancer death in the United States. Treating this life-threatening disease remains challenging due to the lack of effective prognosis, diagnosis and therapy. Apart from pancreatic duct cells, acinar cells may also be the origin of PDAC. During pancreatitis or combined with activating KRas(G12D) mutation, acinar cells lose their cellular identity and undergo a transdifferentiation process called acinar-to-ductal-metaplasia (ADM), forming duct cells which may then transform into pancreatic intraepithelial neoplasia (PanIN) and eventually PDAC. During ADM, the activation of mitogen-activated protein kinases, Wnt, Notch and phosphatidylinositide 3-kinases/Akt signaling inhibits the transcription of acinar-specific genes, including Mist and amylase, but promotes the expression of ductal genes, such as cytokeratin-19. Inhibition of this transdifferentiation process hinders the development of PanIN and PDAC. In addition, the transdifferentiated cells regain acinar identity, indicating ADM may be a reversible process. This provides a new therapeutic direction in treating PDAC through cancer reprogramming. Many studies have already demonstrated the success of switching PanIN/PDAC back to normal cells through the use of PD325901, the expression of E47, and the knockdown of Dickkopf-3. In this review, we discuss the signaling pathways involved in ADM and the therapeutic potential of targeting reprogramming in order to treat PDAC.

  20. Pathology and genetics of pancreatic neoplasms with acinar differentiation.

    PubMed

    Wood, Laura D; Klimstra, David S

    2014-11-01

    Pancreatic neoplasms with acinar differentiation, including acinar cell carcinoma, pancreatoblastoma, and carcinomas with mixed differentiation, are distinctive pancreatic neoplasms with a poor prognosis. These neoplasms are clinically, pathologically, and genetically unique when compared to other more common pancreatic neoplasms. Most occur in adults, although pancreatoblastomas usually affect children under 10 years old. All of these neoplasms exhibit characteristic histologic features including a solid or acinar growth pattern, dense neoplastic cellularity, uniform nuclei with prominent nucleoli, and granular eosinophilic cytoplasm. Exocrine enzymes are detectable by immunohistochemistry and, for carcinomas with mixed differentiation, neuroendocrine or ductal lineage markers are also expressed. The genetic alterations of this family of neoplasms largely differ from conventional ductal adenocarcinomas, with only rare mutations in TP53, KRAS, and p16, but no single gene or neoplastic pathway is consistently altered in acinar neoplasms. Instead, there is striking genomic instability, and a subset of cases has mutations in the APC/β-catenin pathway, mutations in SMAD4, RAF gene family fusions, or microsatellite instability. Therapeutically targetable mutations are often present. This review summarizes the clinical and pathologic features of acinar neoplasms and reviews the current molecular data on these uncommon tumors.

  1. Salivary duct carcinoma of the parotid gland

    PubMed Central

    Mlika, Mona; Kourda, Nadia; Zidi, YSH; Aloui, Raoudha; Zneidi, Nadia; Rammeh, Soumaya; Zermani, Rachida; Jilani, Sarah Ben

    2012-01-01

    Salivary duct carcinoma of the parotid gland is an uncommon tumor, highly aggressive. About 200 cases have been reported in the English literature. Pathomorphologically, these tumors showed great similarities to ductal carcinoma of the female breast, which is why they described this tumor as “salivary duct carcinoma.” The authors describe a new case of salivary duct carcinoma of the parotid gland. We present the case of a 50-year-old patient with progressive facial paralysis. The MRI examination of the head showed two ill-defined formations. A malignant tumor was strongly suspected, so that a total left parotidectomy with excision of the adjacent facial nerve and left lymph node dissection was performed. Microscopic examination concluded to a salivary duct carcinoma of the left parotid gland negative with Her2/neu antibody with lymph node metastasis. There were no recurrences or metastases within 3 years of follow-up. Salivary duct carcinoma of the parotid gland is a rare tumor with an aggressive behavior. This is due to its propensity to infiltrate distant organs. The diagnosis is based on microscopic examination. Treatment modalities are non-consensual, but some authors advocate the necessity of aggressive approach, especially in tumors negative with Heur2/neu antibody. This is due to the fact that the overexpression of this antigen was reported to be associated with a poor prognosis. PMID:22434951

  2. Bilateral Parotid Swelling in Polycystic Ovarian Syndrome.

    PubMed

    Yakubov, Yakov; Mandel, Louis

    2016-05-01

    Polycystic ovarian syndrome (PCOS) is recognized by the presence of polycystic ovaries, irregular menstruation, and increased androgen levels. Many patients have insulin resistance or impaired glucose tolerance and an associated development of type 2 diabetes mellitus. A patient with PCOS is presented whose cosmetic concerns centered on the prolonged existence of substantial bilateral parotid swelling. The pathophysiology, diagnosis, and therapy of sialosis are discussed.

  3. Loss of acinar cell IKKα triggers spontaneous pancreatitis in mice

    PubMed Central

    Li, Ning; Wu, Xuefeng; Holzer, Ryan G.; Lee, Jun-Hee; Todoric, Jelena; Park, Eek-Joong; Ogata, Hisanobu; Gukovskaya, Anna S.; Gukovsky, Ilya; Pizzo, Donald P.; VandenBerg, Scott; Tarin, David; Atay, Çiǧdem; Arkan, Melek C.; Deerinck, Thomas J.; Moscat, Jorge; Diaz-Meco, Maria; Dawson, David; Erkan, Mert; Kleeff, Jörg; Karin, Michael

    2013-01-01

    Chronic pancreatitis is an inflammatory disease that causes progressive destruction of pancreatic acinar cells and, ultimately, loss of pancreatic function. We investigated the role of IκB kinase α (IKKα) in pancreatic homeostasis. Pancreas-specific ablation of IKKα (IkkαΔpan) caused spontaneous and progressive acinar cell vacuolization and death, interstitial fibrosis, inflammation, and circulatory release of pancreatic enzymes, clinical signs resembling those of human chronic pancreatitis. Loss of pancreatic IKKα causes defective autophagic protein degradation, leading to accumulation of p62-mediated protein aggregates and enhanced oxidative and ER stress in acinar cells, but none of these effects is related to NF-κB. Pancreas-specific p62 ablation prevented ER and oxidative stresses and attenuated pancreatitis in IkkαΔpan mice, suggesting that cellular stress induced by p62 aggregates promotes development of pancreatitis. Importantly, downregulation of IKKα and accumulation of p62 aggregates were also observed in chronic human pancreatitis. Our studies demonstrate that IKKα, which may control autophagic protein degradation through its interaction with ATG16L2, plays a critical role in maintaining pancreatic acinar cell homeostasis, whose dysregulation promotes pancreatitis through p62 aggregate accumulation. PMID:23563314

  4. [Acute parotiditis after tracheostomy in Intensive Care].

    PubMed

    Serviá Goixart, L; Badía, M; Campi, D; Trujillano, J; Alcega, R; Vilanova, J

    2006-01-01

    Post-anesthesic parotiditis is a little known entity related with anesthesic procedures but described in any situation that motivates manipulation of the oropharyngeal cavity. Its physiopathological mechanism is not well-defined, although it could have a multifactorial origin. A case of a male who was admitted for post-operative control of brain tumor exeresis and who had preauricular and submaxillary inflammation after a routinely performed tracheostomy is presented. Coincidence with the performing of a tracheostomy required us to propose the differential diagnosis with the complications associated to said surgical act. Post-anesthesic parotiditis, even though it is a rare complication and has no clinical significance, should be kept in mind when there is facial edema after any manipulation of the oropharyngeal cavity.

  5. Parotid salivary secretory pattern in bulimia nervosa.

    PubMed

    Riad, M; Barton, J R; Wilson, J A; Freeman, C P; Maran, A G

    1991-01-01

    Parotid gland enlargement occurs in about 25% of patients with the binge eating syndrome of bulimia nervosa. The parotid salivary secretory patterns in 28 bulimics were determined in order to investigate the functional abnormality in the glands. Bulimia patients had a reduced resting flow rate. Bulimics who developed sialadenosis (4 patients) had reduced resting and stimulated flow rates. The salivary amylase activity was increased in both the resting and stimulated states in bulimics and the sialadenosis group. The resting total protein levels were greater in the bulimics. The electrolyte and immunoglobulin levels were within normal limits. The possibility of protein and enzymatic secretory disturbances due to autonomic nerve disorders as an explanation for the development of sialadenosis in bulimia nervosa is discussed.

  6. Rabbit medicine.

    PubMed

    Jordan, Dinah G

    2007-01-01

    When filling prescriptions for a rabbit, it is important to know whether the rabbit is a pet or is being raised as a source of food for human consumption. Several drugs widely used for pet rabbits are prohibited from exralabel use in animals raised for food production. The list of banned drugs should always be perused prior to filling a prescription for a rabbit being raised for food production. Since no veterinary-approved products exist for rabbits and most medications must be compounded, pharmacists are likely to encounter prescriptions for rabbits in their practice. A basic understanding of rabbit anatomy, physiolgy and common diseases will assist pharmacists in distinguishing between safe and dangerous drugs for administration to rabbits.

  7. Disposable rabbit

    DOEpatents

    Lewis, Leroy C.; Trammell, David R.

    1986-01-01

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  8. Disposal rabbit

    DOEpatents

    Lewis, L.C.; Trammell, D.R.

    1983-10-12

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  9. Valproic acid-associated sialadenosis of the parotid and submandibular glands: diagnostic and therapeutic aspects.

    PubMed

    Mauz, P S; Mörike, K; Kaiserling, E; Brosch, S

    2005-04-01

    Sialadenosis has been defined as a non-inflammatory, parenchymatous salivary gland disease causing recurrent, bilateral swelling of the salivary glands. As an adverse drug reaction of valproic acid, sialadenosis is very rare. To our knowledge, it has been reported only once in the world literature to date. We present herein the case of a patient with valproic acid-associated sialadenosis of both the parotid and submandibular glands. This appears to be the first published case of a patient who received surgical treatment. On light and electron microscopy of all the affected salivary glands, granular sialadenosis with predominantly moderate electron-dense secretory cytoplasmatic granules was observed. No relevant degenerative alterations were seen. There was no histological evidence of peripheral neuropathy of the nerve supply, leading to disordered activity of acinar cells by loss of neurosecretory granules. Lateral parotidectomy, performed under neuromonitoring control for safety reasons, is the treatment of choice for chronic recurrent parotitis that does not respond to conservative therapy, particularly if the cosmetic deformity is unacceptable to the patient. If the submandibular glands are involved, partial removal is recommended.

  10. HIV-associated cystic lesions of the parotid gland.

    PubMed

    Ogasawara, Noriko; Takano, Ken-Ichi; Kobayashi, Hajime; Kikuchi, Keisuke; Matsumiya, Hiroshi; Yoshioka, Iwao; Himi, Tetsuo

    2017-02-01

    We present two cases of an HIV-associated parotid gland cyst. One case was a 36-year-old HIV infected woman. She was diagnosed with HIV infection and presented with slowly enlarged parotid gland cysts together with elevation of HIV viral RNA copies/mL in her serum. She was performed parotid gland biopsy under the general anesthesia. The histopathologic analysis revealed negative HIV p24-antigen in her parotid gland tissue. The other case was a 43-year-old man found his parotid gland swelling shortly after highly active antiretroviral therapy (HAART). He was diagnosed with HIV infection 2 years previously. He had started HAART several days before. He showed exceeding elevation of IgE in his serum. We treated him with medication using anti-histamic drugs for his cyst. A computed tomography scan revealed a complete response of his parotid gland cyst 4 weeks after the medication. His serum IgE level was decreased to half of the level before the medication. These findings suggested that the parotid gland swelling associated with HIV was due to various factors including immune reconstitution inflammatory syndrome (IRIS). In case such a parotid gland swelling, we could avoid invasive treatments.

  11. [The hemodynamics of the parotid glands in children consuming carbohydrates].

    PubMed

    Sigal, Z M; Redinova, T L

    1989-01-01

    The rate of sweets consumption was shown to determine, to a large extent, the salivary glands function. In children rarely consuming sweets the parotid blood flow and salivation increased after intake of a 10% sucrose solution. In children abusing sweets even crystal sugar failed to change the parotid glands blood filling with salivation virtually unaltered.

  12. Parotitis and Sialendoscopy of the Parotid Gland.

    PubMed

    Hernandez, Stephen; Busso, Carlos; Walvekar, Rohan R

    2016-04-01

    Nonneoplastic disorders of the salivary glands involve inflammatory processes. These disorders have been managed conservatively with antibiotics, warm compresses, massage, sialogogues, and adequate hydration. Up to 40% of patients may have an inadequate response or persistent symptoms. When conservative techniques fail, the next step is operative intervention. Sialendoscopy offers a minimally invasive option for the diagnosis and management of chronic inflammatory disorders of the salivary glands and offers the option of gland and function preservation. In this article, we review some of the more common nonneoplastic disorders of the parotid gland, indications for diagnostic and interventional sialendoscopy, and operative techniques.

  13. Acinar neoplasms of the pancreas-A summary of 25 years of research.

    PubMed

    Klimstra, David S; Adsay, Volkan

    2016-09-01

    Our understanding about the family of acinar neoplasms of the pancreas has grown substantially over the past 25 years. The prototype is acinar cell carcinoma, an uncommon variant of pancreatic carcinoma that demonstrates production of pancreatic exocrine enzymes, verifiable using immunohistochemistry, and exhibits characteristic histologic features. Related neoplasms include mixed acinar carcinomas such as mixed acinar neuroendocrine carcinoma and mixed acinar ductal carcinoma. In the pediatric age group, pancreatoblastoma is also closely related. Cystic and extrapancreatic forms have been described. These neoplasms share molecular alterations that are distinct from the more common ductal and neuroendocrine neoplasms of the pancreas. Although there is a broad range of genetic findings, a number of potential therapeutic targets have emerged. This review explores the clinical and pathologic features of pancreatic acinar neoplasms along with their more common molecular phenotypes. The differential diagnosis with other pancreatic neoplasms is explored as well.

  14. Correlation between cellular phone use and epithelial parotid gland malignancies.

    PubMed

    Duan, Y; Zhang, H Z; Bu, R F

    2011-09-01

    The authors investigated the association between cellular phone use and epithelial parotid gland malignancy. The subjects were 136 cases who were treated for this condition at the authors' hospital from January 1993 to March 2010, and 2051 controls who did not have salivary gland tumours and were admitted to the oral and maxillofacial surgery department during the same period. Logistic analysis was used to examine the relationship between cellular phone use and risk of epithelial parotid gland malignancy and mucoepidermoid carcinoma. Overall, the frequency of cellular phone use was not significantly associated with epithelial parotid gland malignancy. Female gender, advanced age, married status, high income, and smoking were associated with an elevated risk of epithelial parotid gland malignancy, especially mucoepidermoid carcinoma. Residence in a rural area was associated with reduced risk of epithelial parotid gland malignancy. The results suggest a possible dose-response relationship of cellular phone use with epithelial parotid gland malignancy. The authors suggest that the association of cellular phone use and epithelial parotid gland malignancy and mucoepidermoid carcinoma requires further investigation with large prospective studies.

  15. Development of a Zealand white rabbit deposition model to study inhalation anthrax.

    PubMed

    Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E; Einstein, Daniel R; Kuprat, Andrew P; Corley, Richard A

    2016-01-01

    Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits.

  16. Development of a Zealand white rabbit deposition model to study inhalation anthrax

    SciTech Connect

    Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E.; Einstein, Daniel R.; Kuprat, Andrew P.; Corley, Richard A.

    2016-01-28

    Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits.

  17. Poorly differentiated carcinoma arising from adenolymphoma of the parotid gland

    PubMed Central

    Ferrero, Stefano; Cattaneo, Laura; Peri, Andrea; Braidotti, Paola; Cioffi, Ugo; Scaramellini, Gabriele; Ciulla, Michele M; De Simone, Matilde; Arizzi, Carmelo; Pignataro, Lorenzo

    2003-01-01

    Background There is only one previous case report of a poorly differentiated carcinoma arising from an adenolymphoma of the parotid gland (Warthin's tumour). The absence of clinical symptoms, and the aspecificity of the radiological pattern make the diagnosis very difficult. Case presentation We here report the case of a 73-year-old man with Warthin's tumour who was brought to our attention because of a swelling in the parotid region. Conclusions In this case with an atypical clinical presentation, the intra-operative examination of a frozen section of the parotid mass allowed us to diagnose the malignant tumour correctly and consequently undertake its radical excision. PMID:12533195

  18. Serotonin promotes acinar dedifferentiation following pancreatitis-induced regeneration in the adult pancreas.

    PubMed

    Saponara, Enrica; Grabliauskaite, Kamile; Bombardo, Marta; Buzzi, Raphael; Silva, Alberto B; Malagola, Ermanno; Tian, Yinghua; Hehl, Adrian B; Schraner, Elisabeth M; Seleznik, Gitta M; Zabel, Anja; Reding, Theresia; Sonda, Sabrina; Graf, Rolf

    2015-12-01

    The exocrine pancreas exhibits a distinctive capacity for tissue regeneration and renewal following injury. This regenerative ability has important implications for a variety of disorders, including pancreatitis and pancreatic cancer, diseases associated with high morbidity and mortality. Thus, understanding its underlying mechanisms may help in developing therapeutic interventions. Serotonin has been recognized as a potent mitogen for a variety of cells and tissues. Here we investigated whether serotonin exerts a mitogenic effect in pancreatic acinar cells in three regenerative models, inflammatory tissue injury following pancreatitis, tissue loss following partial pancreatectomy, and thyroid hormone-stimulated acinar proliferation. Genetic and pharmacological techniques were used to modulate serotonin levels in vivo. Acinar dedifferentiation and cell cycle progression during the regenerative phase were investigated over the course of 2 weeks. By comparing acinar proliferation in the different murine models of regeneration, we found that serotonin did not affect the clonal regeneration of mature acinar cells. Serotonin was, however, required for acinar dedifferentiation following inflammation-mediated tissue injury. Specifically, lack of serotonin resulted in delayed up-regulation of progenitor genes and delayed the formation of acinar-to-ductal metaplasia and defective acinar cell proliferation. We identified serotonin-dependent acinar secretion as a key step in progenitor-based regeneration, as it promoted acinar cell dedifferentiation and the recruitment of type 2 macrophages. Finally, we identified a regulatory Hes1-Ptfa axis in the uninjured adult pancreas, activated by zymogen secretion. Our findings indicated that serotonin plays a critical role in the regeneration of the adult pancreas following pancreatitis by promoting the dedifferentiation of acinar cells.

  19. Solitary fibrous tumor of the parotid gland: Case report

    PubMed Central

    Sousa, Alexandre A.; Souto, Giovanna R.; Sousa, Isabela A.; Mesquita, Ricardo A.; Gomez, Ricardo S.

    2013-01-01

    Solitary fibrous tumor (SFT) is a rare spindle cell neoplasm that usually develops in the pleura and peritoneum. The head and neck region is involved in only 6% of the cases. Involvement of the parotid gland is a rare phenomenon, with only 24 cases reported in the literature. The aim of this study is to report an additional case of SFT affecting the parotid gland, and to review the literature on previously reported cases. The patient was a 42-year-old male with a 4-cm, fibro-elastic, movable, painless nodule in the inferior lobe of the parotid gland. The lesion was surgically excised and, following histopathological and immunohistochemical analysis, a diagnosis of SFT was rendered. The patient has been followed-up for ten months, with no signs of recurrence. Clinical, histopathological, immunohistochemical and treatment aspects of the tumor are discussed. Key words:Solitary fibrous tumor, parotid gland, case report. PMID:24455083

  20. Sialendoscopy-assisted transfacial surgical removal of parotid stones.

    PubMed

    Capaccio, Pasquale; Pasquale, Capaccio; Gaffuri, Michelle; Michele, Gaffuri; Pignataro, Lorenzo; Lorenzo, Pignataro

    2014-12-01

    Minimally invasive surgical approaches to parotid stones (such as extra-corporeal shockwave lithotripsy and sialendoscopy) have proved to be effective in a high percentage of cases, although success depends on factors such as the localisation of the stone, its size and its mobility. The failure rate of 10% is largely due to large and impacted stones and, in such cases, a combined external and sialendoscopic approach can be used to avoid morbidity and the risks of more invasive superficial parotidectomy. We treated eight patients with large parotid stones (>7 mm) using a sialendoscopy-assisted transfacial surgical approach that was effective in all but one case, which was successfully solved by combining this procedure with extra-corporeal lithotripsy and operative sialendoscopy. Our results confirm that the combined approach is a valid alternative to parotidectomy for large parotid stones and should be added to other minimally invasive techniques aimed at restoring the function of the affected parotid gland.

  1. Inflammatory pseudotumor of the parotid gland.

    PubMed

    Barrios-Sánchez, Gracia M; Dean-Ferrer, Alicia; Alamillos-Granados, Francisco J; Ruiz-Masera, Juan José; Zafra-Camacho, Francisco M; García de Marcos, José A; Calderón-Bohórquez, José M

    2005-01-01

    Inflammatory pseudotumor is a term that refers to a reactive pseudoneoplastic disorder that can appear in different locations of the human body. The lung is the most frequently affected organ. The etiology is still unknown. It affects individuals of both sexes and of a wide range of ages. The diagnosis is still difficult and it is based on the histological examination of the lesions composed of four cell-types: histiocytes, myofibroblasts, plasma cells and lymphocytes. With regard to the treatment regimes there is no agreement. Treatment ranges from surgical excision to radiotherapy, chemotherapy or steroids. The purpose of this article is to report one case of inflammatory pseudotumor located in the parotid gland and to make a special point of the difficulty in arriving at a correct diagnosis in order to achieve the most adequate treatment.

  2. Recurrent Parotid Carcinosarcoma in an Asymptomatic Patient

    PubMed Central

    Mansour, Joshua; Mangaonkar, Abhishek; Kota, Vamsi

    2016-01-01

    In this article, we present the case of a 52-year-old male with a history of parotid carcinosarcoma with initial diagnosis being 18 months prior. Initial treatment included a combination of gamma knife surgery coupled with high dosage chemotherapy and X-ray radiation therapy. At the time of follow-up, the patient presented with no complaints and had a nearly normal physical exam with the exception of some facial nerve weakness on the same side as the initial surgery. Despite being asymptomatic, the patient had a significant progression of disease that was manifested with intracranial lesions, multiple pathologic fractures, and a dramatic increase in overall tumor burden. Ultimately, the patient decided to pursue comfort measures only and succumbed to the disease peacefully soon thereafter. PMID:27847832

  3. Sebaceous lymphadenoma of parotid gland in a child.

    PubMed

    Sun, Guowen; Hu, Qingang; Huang, Xiaofeng; Tang, Enyi

    2009-02-01

    Sebaceous lymphadenoma is a rare tumor presenting predominantly in the parotid gland. Most sebaceous lymphadenomas are composed of variably sized sebaceous glands admixed with salivary ducts in a diffuse lymphoid background. The treatment is complete surgical excision, and this tumor is rarely recurrent. Reported here is a case of sebaceous lymphadenoma of the left parotid gland in a 16-year-old boy. A left superficial parotidectomy was performed.

  4. [Mammary analog secretory carcinoma of the parotid gland].

    PubMed

    Guérin, Maxime; Diedhiou, Abdoulaye; Nallet, Emmanuel; Duflo, Suzy; Laé, Marick; Wassef, Michel

    2014-10-01

    Mammary analog secretory carcinoma (MASC) of the parotid gland is a rare and recently described lesion. We report the case of a 46-year-old man with a tumor of the parotid gland which was carried to the diagnosis of MASC. Diagnostic was confirmed by highlighting the ETV6-NTRK3 gene translocation. However, some morphologic and immunohistochemical features are suggestive of this entity. This carcinoma should be distinguished from its main differential diagnoses: acinic cell carcinoma and low grade cribriform cystadenocarcinoma.

  5. Helical Tomotherapy for Parotid Gland Tumors

    SciTech Connect

    Lee, Tae Kyu; Rosen, Isaac I.; Gibbons, John P.; Fields, Robert S.; Hogstrom, Kenneth R.

    2008-03-01

    Purpose: To investigate helical tomotherapy (HT) intensity-modulated radiotherapy (IMRT) as a postoperative treatment for parotid gland tumors. Methods and Materials: Helical tomotherapy plans were developed for 4 patients previously treated with segmental multileaf collimator (SMLC) IMRT. A primary planning target volume (PTV64) and two secondary PTVs (PTV60, PTV54) were defined. The clinical goals from the SMLC plans were applied as closely as possible to the HT planning. The SMLC plans included bolus, whereas HT plans did not. Results: In general, the HT plans showed better target coverage and target dose homogeneity. The minimum doses to the desired coverage volume were greater, on average, in the HT plans for all the targets. Minimum PTV doses were larger, on average, in the HT plans by 4.6 Gy (p = 0.03), 4.8 Gy (p = 0.06), and 4.9 Gy (p = 0.06) for PTV64, PTV60, and PTV54, respectively. Maximum PTV doses were smaller, on average, by 2.9 Gy (p = 0.23), 3.2 Gy (p = 0.02), and 3.6 Gy (p = 0.03) for PTV64, PTV60, and PTV54, respectively. Average dose homogeneity index was statistically smaller in the HT plans, and conformity index was larger for PTV64 in 3 patients. Tumor control probabilities were higher for 3 of the 4 patients. Sparing of normal structures was comparable for the two techniques. There were no significant differences between the normal tissue complication probabilities for the HT and SMLC plans. Conclusions: Helical tomotherapy treatment plans were comparable to or slightly better than SMLC plans. Helical tomotherapy is an effective alternative to SMLC IMRT for treatment of parotid tumors.

  6. An audit of surgery of the parotid gland.

    PubMed Central

    Deans, G. T.; Briggs, K.; Spence, R. A.

    1995-01-01

    The management of patients undergoing 50 surgical procedures to the parotid gland was reviewed. The overall accuracy of fine needle aspiration cytology was 87%, false-positive and false-negative rates for malignant disease both being 4%. The sensitivity, specificity and accuracy of fine needle cytology for malignant parotid tumours was 66%, 95%, and 91%, respectively, that of benign tumours (pleomorphic adenoma or Warthin's tumour) being 88%, 83% and 87%, respectively. Sensitivity, specificity and accuracy for the remaining (principally inflammatory) parotid diseases was 100%, 95% and 96%, respectively. The predictive value of a positive test for malignant tumours, benign tumours and inflammatory conditions was 66%, 94% and 75%, respectively. The negative predictive value for these conditions was 95%, 71% and 100%, respectively. Facial nerve weakness after parotidectomy occurred in three patients (8.8%), being permanent in two cases (both malignant). Although Frey's syndrome was not recorded in any of the notes, careful follow-up revealed two cases (6%). To date there have been no local recurrences after excision of either benign or primary malignant parotid masses. One patient with squamous cell carcinoma metastatic to the parotid gland died, despite block dissection of the neck and radiotherapy. This small series with a limited follow-up suggests that diseases of the parotid gland can be managed by general surgeons with an interest in this field. Although fine needle aspiration and ultrasonic scan may be helpful, the decision to operate should be made on clinical grounds. PMID:7598416

  7. Oxidative stress in alcohol-induced rat parotid sialadenosis.

    PubMed

    Campos, Sara Cristina Gonçalves; Moreira, Denise Aparecida Corrêa; Nunes, Terezinha D'Avila e Silva; Colepicolo, Pio; Brigagão, Maísa Ribeiro Pereira Lima

    2005-07-01

    This study evaluated the effect of chronic ethanol consumption on the oxidative status of rat parotid and submandibular glands. To identify the endogenous response to ethanol ingestion, the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined. In addition, the antioxidant alpha-tocopherol was supplied to the animals in order to estimate its action in ethanol-associated glandular damage. The thiobarbituric acid reactive substances (TBARS), and the protein carbonyl (PC) content, both markers of cellular oxidative stress on lipid and protein structures, respectively, were recorded. Animals subjected to alcohol ingestion showed a low body growth rate with concomitant enlargement of absolute and relative parotid wet weight, compared with pair-fed calorie-controlled rats. Parotid glands of ethanol-treated animals showed increased SOD and GPx activity, and alpha-tocopherol was able to reduce their activities to the control levels. TBARS and PC were enhanced after chronic ethanol treatment in rat parotids. Supplemental alpha-tocopherol suppressed the oxidative ethanol-induced damage in lipid without affecting induced protein oxidation. Submandibular glands revealed no alterations in the weight, enzymatic and oxidative parameters tested due to ethanol and/or alpha-tocopherol ingestion. These findings indicate the involvement of oxidative stress in parotid gland sialadenosis due to ethanol consumption and the capability of alpha-tocopherol to halt lipid damage, although this low-molecular antioxidant compound leads to neither increased glandular weight nor protein oxidation in ethanol-induced parotid alterations.

  8. Cavernous hemangioma of the parotid gland in adults

    PubMed Central

    Peral-Cagigal, Beatriz; Madrigal-Rubiales, Beatriz; Verrier-Hernández, Alberto

    2014-01-01

    Hemangiomas account for 0.4-0.6% of all tumors of the parotid gland and most of them occur in children, nevertheless in adults hemangiomas are very rare. We report the case of a 62 year old woman with a mass in the parotid right tail associated with fluctuating swelling episodes unrelated to meals and with a slowly progressive growth. The provisional diagnosis was a pleomorphic adenoma, so a right superficial parotidectomy was performed. During surgery, the macroscopic appearance makes suspect a vascular lesion. The histopathological result was a cavernous hemangioma. The classic clinical presentation of a parotid hemangioma is an intraglandular mass associated or not with skin lesions characterized by reddish macules and/or papules, and a vibration or pulsation when palpating the parotid region. In imaging tests, phleboliths could be observed which are very suggestive of a hemangioma or a vascular malformation. In the absence of these signs, the diagnosis could be difficult, particularly in an adult due to its low prevalence, with about 50 cases reported worldwide. However a hemangioma should be considered in the differential diagnosis of parotid tumors in adults. Key words:Cavernous hemangioma, parotid gland, superficial parotidectomy, pleomorphic adenoma. PMID:25674332

  9. [Acrylamid- and immunelectrophoretic separations of human parotid secretions from individuals with parotid tumors, chronic parotitis and sialadenosis (author's transl)].

    PubMed

    Eichner, H

    1976-11-01

    After previous examinations in normal parotid glands in this paper secretion of proteins in parotid glands with pleomorphic adenomas, Whartin tumors, parotid carcinomas, chronic parotitis and sialadenosis should be studied. Different discelectrophoretic and immunelectrophoretic runs were done. Thereby we got the following changes in electrophoreses: Pleomorphic adenomas generally show a more palid pattern in band-structure, caused by the diminished proteinconcentration in the secretions. Most remarkable are thereby the c1 and d1-4-bands. Immunelectrophoretic separations are normal. Whartin tumors show a different bandpattern in the anodal near gel region, which is enpowered by immunelectrophoretic runs. Secretions from parotid carcinomas show a characteristic change in bandstructure. There are found added bands which result from serumproteins as immunelectrophoretic examinations proof. The same is found in glands with parotitis in contrary to glands with sialadenosis.

  10. Functional somatostatin receptors on a rat pancreatic acinar cell line

    SciTech Connect

    Viguerie, N.; Tahiri-Jouti, N.; Esteve, J.P.; Clerc, P.; Logsdon, C.; Svoboda, M.; Susini, C.; Vaysse, N.; Ribet, A. Mount Zion Hospital and Medical Center, San Francisco, CA Universite Libre de Bruxelles, Brussels )

    1988-07-01

    Somatostatin receptors from a rat pancreatic acinar cell line, AR4-2J, were characterized biochemically, structurally, and functionally. Binding of {sup 125}I-(Tyr{sup 11})Somatostatin to AR4-2J cells was saturable, exhibiting a single class of high-affinity binding sites with a maximal binding capacity of 258 {plus minus} 20 fmol/10{sup 6} cells. Somatostatin receptor structure was analyzed by covalently cross-linking {sup 125}I-(Tyr{sup 11})somatostatin to its plasma membrane receptors. Gel electrophoresis and autoradiography of cross-linked proteins revealed a peptide containing the somatostatin receptor. Somatostatin inhibited vasoactive intestinal peptide (VIP)-stimulated adenosine 3{prime},5{prime}-cyclic monophosphate (cAMP) formation in a dose-dependent manner. The concentration of somatostatin that caused half-maximal inhibition of cAMP formation was close to the receptor affinity for somatostatin. Pertussis toxin pretreatment of AR4-2J cells prevented somatostatin inhibition of VIP-stimulated cAMP formation as well as somatostatin binding. The authors conclude that AR4-2J cells exhibit functional somatostatin receptors that retain both specificity and affinity of the pancreatic acinar cell somatostatin receptors and act via the pertussis toxin-sensitive guanine nucleotide-binding protein N{sub i} to inhibit adenylate cyclase.

  11. The effects of sigma ligands on protein release from lacrimal acinar cells: a potential agonist/antagonist assay.

    PubMed

    Schoenwald, R D; Barfknecht, C F; Shirolkar, S; Xia, E

    1995-03-03

    Sigma receptor antagonists have been proposed as leading clinical candidates for use in various psychotic disorders. Prior to clinical testing, it is imperative that a new agent be correctly identified as an antagonist and not an agonist since the latter may worsen the psychosis. For sigma-ligands many behavioral and pharmacological assays have been developed in an attempt to classify agonist/antagonist activity. These assays evaluate a response or a behavior in an animal model that can be related to clinical efficacy. However, is the action by the presumed antagonist a consequence of sigma-receptor activity? Previously we have identified sigma-receptors in acinar cells of the main lacrimal gland of the New Zealand white rabbit and have measured protein release after the addition of various N,N-disubstituted phenylalkylamine derivatives known to be sigma-ligands by receptor binding studies. Although protein release from acinar cells has been attributed to either muscarinic or alpha-adrenergic stimulation, protein release from sigma-receptor stimulation was also confirmed. In the reported studies here, we isolated and incubated acinar cells with varying concentrations of known sigma-ligands and measured protein concentration. A knowledge of the receptor profile for the disubstituted phenylalkylamines permitted experiments to be designed in which various alpha, muscarinic, serotonergic, and dopaminergic antagonists could be added in equimolar concentrations. Under the conditions of these experiments, statistically significant increases in protein release for sigma-ligands could be attributed to stimulation of sigma-receptors. Haloperidol, an apparent sigma-antagonist, caused a statistically significant decrease in protein release and also inhibited protein release when tested with a known sigma-ligand, AF2975 [N,N-dimethyl-2-phenylethylamine]. In this system, stimulation and inhibition of protein release were defined as agonist and antagonist behavior, respectively

  12. Relationships between levels of lysozyme, lactoferrin, salivary peroxidase, and secretory immunoglobulin A in stimulated parotid saliva.

    PubMed Central

    Rudney, J D; Smith, Q T

    1985-01-01

    Recent studies suggest that salivary lysozyme (Lz), lactoferrin (Lf), peroxidase (Spx), and secretory immunoglobulin A (sIgA) may interact in a common antimicrobial system. A multiple protein approach therefore may be needed to determine the role of this system in oral health and ecology. In the present study we investigate the relationships between levels of Lz, Lf, Spx, and sIgA (adjusted for flow rate and total protein) in stimulated parotid saliva from 44 dental students. Principal components analysis was used to determine major patterns of intercorrelation between variables; cluster analysis was used to identify groups of subjects with similar salivary profiles for Lz, Lf, Spx, and sIgA. Spx tended to vary independently of Lz and Lf, which, in turn, tended to vary together. sIgA showed a weak negative relationship with Spx and a weak positive relationship with Lz and Lf. Six major clusters of subjects with similar antimicrobial protein profiles were found. These were significantly different at P less than 0.0001. Spx was the most important determinant of cluster membership followed (in order of importance) by Lz, Lf, and sIgA. Cluster profiles were Spx-, sIgAmu, Lf-, Lz-; Spx-, sIgA+, Lfmu, Lz+; Spxmu, sIgAmu, Lfmu, Lzmu; Spx+, sIgA-, Lf-, Lz-; Spx+, sIgAmu, Lf+, Lz-; and Spx+, sIgAmu, Lf+, Lz+ (-, mu, and + refer to the position of the cluster mean each variable relative to the overall mean for that variable). Results suggest that clusters may be a product of independent variation in the secretory activity of acinar and intercalated duct cells. PMID:4030086

  13. PNA lectin for purifying mouse acinar cells from the inflamed pancreas.

    PubMed

    Xiao, Xiangwei; Fischbach, Shane; Fusco, Joseph; Zimmerman, Ray; Song, Zewen; Nebres, Philip; Ricks, David Matthew; Prasadan, Krishna; Shiota, Chiyo; Husain, Sohail Z; Gittes, George K

    2016-02-17

    Better methods for purifying human or mouse acinar cells without the need for genetic modification are needed. Such techniques would be advantageous for the specific study of certain mechanisms, such as acinar-to-beta-cell reprogramming and pancreatitis. Ulex Europaeus Agglutinin I (UEA-I) lectin has been used to label and isolate acinar cells from the pancreas. However, the purity of the UEA-I-positive cell fraction has not been fully evaluated. Here, we screened 20 widely used lectins for their binding specificity for major pancreatic cell types, and found that UEA-I and Peanut agglutinin (PNA) have a specific affinity for acinar cells in the mouse pancreas, with minimal affinity for other major pancreatic cell types including endocrine cells, duct cells and endothelial cells. Moreover, PNA-purified acinar cells were less contaminated with mesenchymal and inflammatory cells, compared to UEA-I purified acinar cells. Thus, UEA-I and PNA appear to be excellent lectins for pancreatic acinar cell purification. PNA may be a better choice in situations where mesenchymal cells or inflammatory cells are significantly increased in the pancreas, such as type 1 diabetes, pancreatitis and pancreatic cancer.

  14. PNA lectin for purifying mouse acinar cells from the inflamed pancreas

    PubMed Central

    Xiao, Xiangwei; Fischbach, Shane; Fusco, Joseph; Zimmerman, Ray; Song, Zewen; Nebres, Philip; Ricks, David Matthew; Prasadan, Krishna; Shiota, Chiyo; Husain, Sohail Z.; Gittes, George K.

    2016-01-01

    Better methods for purifying human or mouse acinar cells without the need for genetic modification are needed. Such techniques would be advantageous for the specific study of certain mechanisms, such as acinar-to-beta-cell reprogramming and pancreatitis. Ulex Europaeus Agglutinin I (UEA-I) lectin has been used to label and isolate acinar cells from the pancreas. However, the purity of the UEA-I-positive cell fraction has not been fully evaluated. Here, we screened 20 widely used lectins for their binding specificity for major pancreatic cell types, and found that UEA-I and Peanut agglutinin (PNA) have a specific affinity for acinar cells in the mouse pancreas, with minimal affinity for other major pancreatic cell types including endocrine cells, duct cells and endothelial cells. Moreover, PNA-purified acinar cells were less contaminated with mesenchymal and inflammatory cells, compared to UEA-I purified acinar cells. Thus, UEA-I and PNA appear to be excellent lectins for pancreatic acinar cell purification. PNA may be a better choice in situations where mesenchymal cells or inflammatory cells are significantly increased in the pancreas, such as type 1 diabetes, pancreatitis and pancreatic cancer. PMID:26884345

  15. Acinar cell carcinoma of exocrine pancreas in two horses.

    PubMed

    de Brot, S; Junge, H; Hilbe, M

    2014-05-01

    Two horses were presented with non-specific clinical signs of several weeks' duration and were humanely destroyed due to a poor prognosis. At necropsy examination, both horses had multiple small, white nodules replacing pancreatic tissue and involving the serosal surface of the abdominal cavity, the liver and the lung. Microscopically, neoplastic cells were organized in acini and contained abundant (case 1) or sparse (horse 2) intracytoplasmic zymogen granules. Immunohistochemically, both tumours expressed amylase and pan-cytokeratin, but not insulin or neuron-specific enolase. In case 2, a low percentage of neoplastic cells expressed glucagon and synaptophysin. The presence of zymogen granules was confirmed in both cases by electron microscopy and occasional fibrillary or glucagon granules were observed in cases 1 and 2, respectively. A diagnosis of pancreatic acinar cell carcinoma was established in both horses.

  16. Interventional sialendoscopy for parotid ductal calculi: our preliminary experience.

    PubMed

    Singh, P P; Gupta, Neelima; Goyal, Arun; Tomar, Sanjeev

    2012-09-01

    With this article we present our initial experience with interventional sialendoscopy of the parotid duct for the parotid calculi. We carried out a prospective study of patients of parotid calculi in a tertiary referral centre. Diagnostic and interventional sialendoscopy was performed in five cases of parotid calculi. The outcome was classified on the basis of clearance of the lumen of the duct and resolution of symptoms. Diagnostic sialendoscopy was able to diagnose the calculus in all cases. Interventional sialendoscopy was done under general anesthesia in all cases and calculus was successfully removed. The average size of sialolith was 8.2 mm. No complications occurred in any of the cases. Check sialendoscopy was done in all cases after a minimum follow up of 6 months, which showed the duct lumen to be free of stone with no stricture of the duct. Sialendoscopy is an optimal technique for removal of intraductal parotid calculi and avoids removal of the gland. In our series there was no associated morbidity and complication.

  17. Parotid or carotid? Misled by site.

    PubMed

    Tyagi, Ruchita; Munjal, Manish; Kaur, Pavneet; Kaur, Harpreet; Sood, Neena

    2017-03-06

    We present an interesting scenario where a 64 years old male presented with a long standing painless, infra-auricular swelling, which had progressively increased in size. Based on the site, the clinical impression was of a salivary gland lesion and FNAC was performed. The smears were unusually cellular and had necrotic background. The cytological diagnosis was a cystic neoplasm of salivary gland, possibly mucoepidermoid carcinoma. Warthin's tumor was also kept in differential. However, the radiological investigations, which were made available after the FNAC report were conflicting with cytological diagnosis of a malignancy and were characteristic of a carotid body tumor, generally a benign neoplasm. Surgical excision of the tumor with regional lymph node sampling was done and histopathological examination solved the puzzle by revealing metastasis of paraganglioma to right posterior triangle lymph nodes. This case is unique because of the unusual presentation of a malignant paraganglioma as an infra-auricular swelling, which was clinically considered as a parotid tumor. The clinician as well as the pathologist need to be aware of such diagnostic pitfall. Diagn. Cytopathol. 2017. © 2017 Wiley Periodicals, Inc.

  18. Human Parotid Gland Alpha-Amylase Secretion as a Function of Chronic Hyperbaric Exposure

    DTIC Science & Technology

    1979-01-01

    parotid ...Pullman, WA 99163 Gilman, S. C, G. J. Fischer, R. J. Biersner, R. D. Thornton, and D. A. Miller. 1979. Human parotid gland alpha-amylase secretion...as a function of chronic hyperbaric exposure. Undersea Biomed. Res. 6(3):303-307.—Secretion of a-amylase by the human parotid gland increased

  19. Oncocytoma of the Deep Lobe of the Parotid Gland

    PubMed Central

    Popovski, Vladimir; Benedetti, Alberto; Monevska, Danica Popovik; Grcev, Aleksandar; Serafimovski, Predrag; Pecanovski, Ruse; Stamatoski, Aleksandar

    2016-01-01

    BACKGROUND: Oncocytoma or oxyphilic adenoma is uncommon salivary gland tumour, occurs predominantly in the in patients older than 60 years of age. Clinically oncocytoma resemble other salivary tumours while histology is typically consisting of oncocytes with many hyperplastic mitochondria. It usually occurs in the parotid gland. Because the features of oncocytoma are similar to those of other benign and low-grade malignant salivary tumours, clinical diagnosis is often challenging. CASE PRESENTATION: This report presents the pathologic and imaging findings of an oncocytoma arising in the deep lobe of the right parotid gland in a 74-year-old male. Oncocytoma was diagnosed on the basis of histological, magnetic resonance imaging (MRI), scintigraphic findings and fine needle aspiration cytology (FNAC). CONCLUSION: This case was unique because in the literature there are few articles about the rare presentation and deep lobe location of this type of parotid oncocytoma. PMID:27335603

  20. Sialolipoma of the parotid gland: a rare entity.

    PubMed

    Pandey, Diwakar; Vats, Manu; Akhtar, Azaz; Pathania, Om Prakash

    2015-06-16

    Lipomatous neoplasms of the parotid gland are rare tumours contributing from 0.6% to 4.4% to all parotid neoplasms with most series reporting an incidence of 1%. It is extremely rare in females, being 10 times more common in males, and the most common age of presentation is the five to sixth decade. Numerous histological variants of salivary gland lipoma have been described. Sialolipoma is a rare variant having proliferation of mature adipocytes with secondary entrapment of the normal salivary gland element. We report a rare case of sialolipoma in the right parotid of a 45-year-old woman who was treated with superficial parotidectomy. Postoperative recovery as well as follow-up has been uneventful.

  1. Remarkable Triple Pleomorphic Adenoma Affecting both Parotid and Submandibular Glands

    PubMed Central

    Pingarrón-Martín, Lorena; Arias-Gallo, L. J.; Demaría-Martínez, G.; Chamorro Pons, M.

    2014-01-01

    The objective of this article is to present the first case reported in the literature of metachronous pleomorphic adenoma of bilateral parotid glands and submaxillary gland. The authors report the case of a 27-year-old female with metachronous mixed tumors in her right parotid and submandibular glands. The patient has no history of previous radiotherapy. All three lesions were diagnosed by fine-needle aspiration. The histopathologic evaluation of all three major salivary gland masses demonstrated pleomorphic adenomas, with no occult malignancy observed on serial sections. The presentation of pleomorphic adenomas in the parotids and submandibular glands probably represents three unrelated primary sites of tumor, yet the possibility of metastasis from one gland to the other cannot be excluded. PMID:26000084

  2. Step-by-step protocol to perfuse and dissect the mouse parotid gland and isolation of high-quality RNA from murine and human parotid tissue.

    PubMed

    Watermann, Christoph; Valerius, Klaus Peter; Wagner, Steffen; Wittekindt, Claus; Klussmann, Jens Peter; Baumgart-Vogt, Eveline; Karnati, Srikanth

    2016-04-01

    Macroscopic identification and surgical removal of the mouse parotid gland is demanding because of its anatomic location and size. Moreover, the mouse parotid gland contains high concentrations of RNases, making it difficult to isolate high-quality RNA. So far, appropriate methods for optimal perfusion-fixation and dissection of mouse parotid glands, as well as the isolation of high quality RNA from this tissue, are not available. Here we present a simple, optimized, step-by-step surgical method to perfuse and isolate murine parotid glands. We also compared two common RNA extraction methods (RNeasy Mini Kit versus TRIzol) for their yields of high-quality, intact RNA from human and murine parotid gland tissues that were either snap-frozen or immersed in RNAlater stabilization solution. Mouse parotid tissue that was perfused and immersed in RNAlater and human samples immersed in RNAlater exhibited the best RNA quality, independent of the isolation method.

  3. [Lupus erythematosus panniculitis presenting as palpebral edema and parotiditis].

    PubMed

    Pérez-Pastor, G; Valcuende, F; Tomás, G; Moreno, M

    2007-10-01

    Lupus erythematosus panniculitis or lupus erythematosus profundus is characterized by inflammation of the deep dermis and subcutaneous tissue. It can occur in isolation or associated with chronic systemic or discoid lupus erythematosus. It usually consists of nodules and hardened subcutaneous plaques on the forehead, cheeks, proximal extremities, and buttocks. Periorbital and parotid involvement are rare and can lead to misdiagnosis. We present the case of a patient with lupus erythematosus panniculitis who presented with palpebral edema and involvement of the periocular fat and parotid gland.

  4. Pancreatic acinar cells: effects of micro-ionophoretic polypeptide application on membrane potential and resistance.

    PubMed

    Petersen, O H; Philpott, H G

    1979-05-01

    1. Acinar cell membrane potential and resistance were measured from superfused segments of mouse pancreas, in vitro, using intracellular glass micro-electrodes. One or two extracellular micropipettes containing caerulein, bombesin nonapeptide (Bn) or acetylcholine (ACh) were placed near to the surface of the impaled acinus. The secretagogues were ejected rapidly from the micropipettes by ionophoresis.2. Each secretagogue evoked a similar electrical response from the impaled acinar cell: membrane depolarization and a simultaneous reduction in input resistance. The duration of cell activation from caerulein ionophoresis was longer than that observed for ACh and Bn. The cell response to the peptide hormone applications could be repeated in the presence of atropine.3. The minimum interval before the onset of cell depolarization after caerulein ionophoresis was determined. Values ranged between 500 and 1000 msec. The minimum latencies after Bn ionophoresis were 500-1400 msec.4. With two electrodes inserted into electrically coupled acinar cells, direct measurements of the caerulein and Bn null potentials were made. At high negative membrane potentials an enhanced depolarization was evoked by caerulein ionophoresis. At low negative membrane potentials the caerulein stimulation produced a diminished depolarization, and at membrane potentials less than - 10 mV acinar cell hyperpolarizations were observed. A similar series of responses was obtained in experiments where Bn ionophoresis was used. The caerulein and the Bn null potentials were always contained within - 10 to - 15 mV.5. The results describe the almost identical electrical response of acinar cells to stimulation by ACh, caerulein and bombesin. All three secretagogues have similar null potentials and latencies of activation on acinar cells. The bombesin latency responses appear as short as those measured for caerulein and provide electro-physiological evidence that Bn acts directly on acinar cells. The findings

  5. A Computer-Based Automated Algorithm for Assessing Acinar Cell Loss after Experimental Pancreatitis

    PubMed Central

    Eisses, John F.; Davis, Amy W.; Tosun, Akif Burak; Dionise, Zachary R.; Chen, Cheng; Ozolek, John A.; Rohde, Gustavo K.; Husain, Sohail Z.

    2014-01-01

    The change in exocrine mass is an important parameter to follow in experimental models of pancreatic injury and regeneration. However, at present, the quantitative assessment of exocrine content by histology is tedious and operator-dependent, requiring manual assessment of acinar area on serial pancreatic sections. In this study, we utilized a novel computer-generated learning algorithm to construct an accurate and rapid method of quantifying acinar content. The algorithm works by learning differences in pixel characteristics from input examples provided by human experts. HE-stained pancreatic sections were obtained in mice recovering from a 2-day, hourly caerulein hyperstimulation model of experimental pancreatitis. For training data, a pathologist carefully outlined discrete regions of acinar and non-acinar tissue in 21 sections at various stages of pancreatic injury and recovery (termed the “ground truth”). After the expert defined the ground truth, the computer was able to develop a prediction rule that was then applied to a unique set of high-resolution images in order to validate the process. For baseline, non-injured pancreatic sections, the software demonstrated close agreement with the ground truth in identifying baseline acinar tissue area with only a difference of 1%±0.05% (p = 0.21). Within regions of injured tissue, the software reported a difference of 2.5%±0.04% in acinar area compared with the pathologist (p = 0.47). Surprisingly, on detailed morphological examination, the discrepancy was primarily because the software outlined acini and excluded inter-acinar and luminal white space with greater precision. The findings suggest that the software will be of great potential benefit to both clinicians and researchers in quantifying pancreatic acinar cell flux in the injured and recovering pancreas. PMID:25343460

  6. A comparison of mean parotid gland dose with measures of parotid gland function after radiotherapy for head-and-neck cancer: Implications for future trials

    SciTech Connect

    Roesink, Judith M. . E-mail: J.M.Roesink@azu.nl; Schipper, Maria; Busschers, Wim; Raaijmakers, Cornelis P.J.; Terhaard, Chris H.J.

    2005-11-15

    Purpose: To determine the most adequate parameter to measure the consequences of reducing the parotid gland dose. Methods and Materials: One hundred eight patients treated with radiotherapy for various malignancies of the head and neck were prospectively evaluated using three methods. Parotid gland function was objectively determined by measuring stimulated parotid flow using Lashley cups and scintigraphy. To assess xerostomia-related quality of life, the head-and-neck cancer module European Organization for Research and Treatment of Cancer QLQ (Quality of Life Questionnaire) H and N35 was used. Measurements took place before radiotherapy and 6 weeks and 12 months after the completion of radiotherapy. Complication was defined for each method using cutoff values. The correlation between these complications and the mean parotid gland dose was investigated to find the best measure for parotid gland function. Results: For both flow and scintigraphy data, the best definition for objective parotid gland toxicity seemed to be reduction of stimulated parotid flow to {<=}25% of the preradiotherapy flow. Of all the subjective variables, only the single item dry mouth 6 weeks after radiotherapy was found to be significant. The best correlation with the mean parotid gland dose was found for the stimulated flow measurements. The predictive ability was the highest for the time point 1 year after radiotherapy. Subjective findings did not correlate with the mean parotid dose. Conclusions: Stimulated flow measurements using Lashley cups, with a complication defined as flow {<=}25% of the preradiotherapy output, correlated best with the mean parotid gland dose. When reduction of the mean dose to the parotid gland is intended, the stimulated flow measurement is the best method for evaluating parotid gland function.

  7. Live pancreatic acinar imaging of exocytosis using syncollin-pHluorin.

    PubMed

    Fernandez, Nestor A; Liang, Tao; Gaisano, Herbert Y

    2011-06-01

    In this report, a novel live acinar exocytosis imaging technique is described. An adenovirus was engineered, encoding for an endogenous zymogen granule (ZG) protein (syncollin) fused to pHluorin, a pH-dependent green fluorescent protein (GFP). Short-term culture of mouse acini infected with this virus permits exogenous adenoviral protein expression while retaining acinar secretory competence and cell polarity. The syncollin-pHluorin fusion protein was shown to be correctly localized to ZGs, and the pH-dependent fluorescence of pHluorin was retained. Coupled with the use of a spinning disk confocal microscope, the syncollin-pHluorin fusion protein exploits the ZG luminal pH changes that occur during exocytosis to visualize exocytic events of live acinar cells in real-time with high spatial resolution in three dimensions. Apical and basolateral exocytic events were observed on stimulation of acinar cells with maximal and supramaximal cholecystokinin concentrations, respectively. Sequential exocytic events were also observed. Coupled with the use of transgenic mice and/or adenovirus-mediated protein expression, this syncollin-pHluorin imaging method offers a superior approach to studying pancreatic acinar exocytosis. This assay can also be applied to acinar disease models to elucidate the mechanisms implicated in pancreatitis.

  8. Duct Cells Contribute to Regeneration of Endocrine and Acinar Cells Following Pancreatic Damage in Adult Mice

    PubMed Central

    CRISCIMANNA, ANGELA; SPEICHER, JULIE A.; HOUSHMAND, GOLBAHAR; SHIOTA, CHIYO; PRASADAN, KRISHNA; Ji, BAOAN; LOGSDON, CRAIG D.; GITTES, GEORGE K.; ESNI, FARZAD

    2015-01-01

    BACKGROUND & AIMS There have been conflicting results on a cell of origin in pancreatic regeneration. These discrepancies predominantly stem from lack of specific markers for the pancreatic precursors/stem cells, as well as differences in the targeted cells and severity of tissue injury in the experimental models so far proposed. We attempted to create a model that used diphtheria toxin receptor (DTR) to ablate specific cell populations, control the extent of injury, and avoid induction of the inflammatory response. METHODS To target specific types of pancreatic cells, we crossed R26DTR or R26dtR/lacZ mice with transgenic mice that express the Cre recombinase in the pancreas, under control of the Pdx1 (global pancreatic) or elastase (acinar-specific) promoters. RESULTS Exposure of PdxCre;R26DTR mice to diphtheria toxin resulted in extensive ablation of acinar and endocrine tissues but not ductal cells. Surviving cells within the ductal compartment contributed to regeneration of endocrine and acinar cells via recapitulation of the embryonic pancreatic developmental program. However, following selective ablation of acinar tissue in ElaCre-ERT2;R26DTR mice, regeneration likely occurred by reprogramming of ductal cells to acinar lineage. CONCLUSIONS In the pancreas of adult mice, epithelial cells within the ductal compartment contribute to regeneration of endocrine and acinar cells. The severity of injury determines the regenerative mechanisms and cell types that contribute to this process. PMID:21763240

  9. Basal autophagy maintains pancreatic acinar cell homeostasis and protein synthesis and prevents ER stress

    PubMed Central

    Antonucci, Laura; Fagman, Johan B.; Kim, Ju Youn; Todoric, Jelena; Gukovsky, Ilya; Mackey, Mason; Ellisman, Mark H.; Karin, Michael

    2015-01-01

    Pancreatic acinar cells possess very high protein synthetic rates as they need to produce and secrete large amounts of digestive enzymes. Acinar cell damage and dysfunction cause malnutrition and pancreatitis, and inflammation of the exocrine pancreas that promotes development of pancreatic ductal adenocarcinoma (PDAC), a deadly pancreatic neoplasm. The cellular and molecular mechanisms that maintain acinar cell function and whose dysregulation can lead to tissue damage and chronic pancreatitis are poorly understood. It was suggested that autophagy, the principal cellular degradative pathway, is impaired in pancreatitis, but it is unknown whether impaired autophagy is a cause or a consequence of pancreatitis. To address this question, we generated Atg7Δpan mice that lack the essential autophagy-related protein 7 (ATG7) in pancreatic epithelial cells. Atg7Δpan mice exhibit severe acinar cell degeneration, leading to pancreatic inflammation and extensive fibrosis. Whereas ATG7 loss leads to the expected decrease in autophagic flux, it also results in endoplasmic reticulum (ER) stress, accumulation of dysfunctional mitochondria, oxidative stress, activation of AMPK, and a marked decrease in protein synthetic capacity that is accompanied by loss of rough ER. Atg7Δpan mice also exhibit spontaneous activation of regenerative mechanisms that initiate acinar-to-ductal metaplasia (ADM), a process that replaces damaged acinar cells with duct-like structures. PMID:26512112

  10. Involvement of thrombopoietin in acinar cell necrosis in L-arginine-induced acute pancreatitis in mice.

    PubMed

    Shen, Jiaqing; Wan, Rong; Hu, Guoyong; Wang, Feng; Shen, Jie; Wang, Xingpeng

    2012-10-01

    Thrombopoietin (TPO) plays an important role in injuries of different tissues. However, the role of TPO in acute pancreatitis (AP) is not yet known. The aim of the study was to determine the involvement of TPO in AP. Serum TPO was assayed in necrotizing pancreatitis induced by L-arginine in mice. Recombinant TPO and anti-TPO antibody were given to mice with necrotizing pancreatitis. Amylase, lipase, lactate dehydrogenase, myeloperoxidase activity and pancreatic water content were assayed in serum and tissue samples. Pancreas and lung tissue samples were also collected for histological evaluation. Immunohistochemistry of amylase α and PCNA were applied for the study of acinar regeneration and TUNEL assay for the detection of apoptosis in the pancreas. Increased levels of serum TPO were found in necrotizing pancreatitis. After TPO administration, more severe acinar necrosis was found and blockade of TPO reduced the acinar necrosis in this AP model. Acinar regeneration and apoptosis in the pancreas were affected by TPO and antibody treatment in necrotizing pancreatitis. The severity of pancreatitis-associated lung injury was worsened after TPO treatment, but attenuated after Anti-TPO antibody treatment. In conclusion, serum TPO is up-regulated in the necrotizing pancreatitis induced by L-arginine in mice and may be a risk factor for the pancreatic acinar necrosis in AP. As a pro-necrotic factor, blockade of TPO can attenuate the acinar necrosis in AP and may be a possible therapeutic intervention for AP.

  11. Parotid salivary duct sialocele associated with glandular duct stenosis in a cat.

    PubMed

    Vallefuoco, Rosario; Jardel, Nicolas; El Mrini, Meryem; Stambouli, Fouzia; Cordonnier, Nathalie

    2011-10-01

    Feline parotid salivary duct sialocele is an uncommon disorder that has been previously reported in association with traumatic rupture of the duct in only two cats. Both cases were successfully treated by proximal duct ligation. We describe the successful surgical treatment of a parotid duct sialocele, secondary to spontaneous salivary duct stenosis, in an adult domestic shorthair cat. The cat was referred for assessment of a recurrent fluid-filled swelling on the left side of the face. Cytology of the aspirated fluid was consistent with serous saliva. The anatomical localisation of the lesion and the nature of the fluid were indicative of parotid gland/duct involvement. Retrograde sialography by parotid duct cannulation was unsuccessful because the left parotid duct opening was stenosed and obstructed by scar tissue. Surgical exploration revealed a parotid salivary duct sialocele, which was completely removed along with the parotid gland without complications.

  12. Effect of Cisplatin on Parotid Gland Function in Concomitant Radiochemotherapy

    SciTech Connect

    Hey, Jeremias; Setz, Juergen; Gerlach, Reinhard; Vordermark, Dirk; Gernhardt, Christian R.; Kuhnt, Thomas

    2009-12-01

    Purpose: To determine the influence of concomitant radiochemotherapy with cisplatin on parotid gland tissue complication probability. Methods and Materials: Patients treated with either radiotherapy (n = 61) or concomitant radiochemotherapy with cisplatin (n = 36) for head-and-neck cancer were prospectively evaluated. The dose and volume distributions of the parotid glands were noted in dose-volume histograms. Stimulated salivary flow rates were measured before, during the 2nd and 6th weeks and at 4 weeks and 6 months after the treatment. The data were fit using the normal tissue complication probability model of Lyman. Complication was defined as a reduction of the salivary flow rate to less than 25% of the pretreatment flow rate. Results: The normal tissue complication probability model parameter TD{sub 50} (the dose leading to a complication probability of 50%) was found to be 32.2 Gy at 4 weeks and 32.1 Gy at 6 months for concomitant radiochemotherapy and 41.1 Gy at 4 weeks and 39.6 Gy at 6 months for radiotherapy. The tolerated dose for concomitant radiochemotherapy was at least 7 to 8 Gy lower than for radiotherapy alone at TD{sub 50}. Conclusions: In this study, the concomitant radiochemotherapy tended to cause a higher probability of parotid gland tissue damage. Advanced radiotherapy planning approaches such as intensity-modulated radiotherapy may be partiticularly important for parotid sparing in radiochemotherapy because of cisplatin-related increased radiosensitivity of glands.

  13. Cystic Dilatation of the Parotid Duct of a Goat

    PubMed Central

    Slocombe, R. F.

    1980-01-01

    Cystic dilatation of the parotid duct of a goat was diagnosed by exploratory surgery and analysis of cyst contents. The cyst and its associated salivary gland were surgically removed. This case is compared with the more common salivary mucocele. ImagesFigure 1. PMID:7397617

  14. Differential Diagnosis of Parotid Lipoma in a Breast Ca Patient

    PubMed Central

    2017-01-01

    Lipomas are common benign tumors usually detected on the torso, neck, upper thighs, and upper arms. However, they are rarely found in the parotid gland region. Because of their rarity at this site, they are not often considered in the differential diagnosis of parotid tumors. This report describes a rare case of a lipoma in the superficial lobe of parotid gland. A 71-year-old female patient admitted to our department complaining about swelling and pain in the posterior area of the left mandibular region since one month. Her medical history included mastectomy after breast CA fifteen years ago. Clinical examination revealed a smooth-surfaced, soft, and painful mass, with well-defined margins in the left mandibular region. Differential diagnosis of metastasis, inflammatory neck swellings, and benign salivary gland tumors were considered for the patient. Advanced imaging methods such as ultrasonography and contrast tomography revealed that the lesion was a lipoma of parotid gland. A surgical intervention under general anesthesia was planned for the removal of the mass; however patient refused the surgical treatment. Patient was placed on six-month periodic recall. This article reviews the radiographic appearance and differential diagnoses of lipoma in this rare location. PMID:28255469

  15. [A bilateral epithelial myoepithelial carcinoma of the parotid gland].

    PubMed

    Tauziède-Espariat, Arnault; Raffoul, Johnny; Sun, Shan Rong; Monnin, Christine; Lassabe, Catherine; Costes, Valérie

    2015-12-01

    We report the case of a 52-year-old man, who was admitted in the department of otorhinolaryngology for a mass of the right parotid gland. The radiological and clinical hypothesis was a squamous cell carcinoma. Histopathological examination revealed a biphasic proliferation composed of epithelial cells arranged in a tubular pattern stained with cytokeratins 5-6 and 7 and EMA surrounded by clear myoepithelial cells stained with smooth muscle actin and p63. Ki-67 labeling index was low. The diagnosis of epithelial myoepithelial carcinoma was proposed. One year after, the patient noticed a centimetric mass of the left parotid gland. The radiological hypothesis was the presence of an intraparotidian lymph node. Histopathological examination showed a second epithelial myoepithelial carcinoma. This is an uncommon neoplasm comprising approximately 1% of all salivary gland tumours, affecting mainly the parotid gland. It is occurring preferably in patients older than 60years old. This is a low-grade malignant tumour with tendency to local recurrence and lymph node metastatic potential. We describe an exceptional bilateral epithelial myoepithelial carcinoma of the parotid gland.

  16. Canalicular adenoma: a case report of an unusual parotid lesion

    PubMed Central

    Butler, Colin; Kulendra, Kevin N; Menon, Gopind; D’Souza, Alwyn R

    2009-01-01

    The present report describes a case of an 85-year-old woman who underwent an excisional biopsy of a preauricular lesion centred over the zygoma and subsequently developed an immediate iatrogenic facial palsy. Histopathological diagnosis revealed a canalicular adenoma of the parotid gland. PMID:21686469

  17. [A case of parotid pleomorphic adenoma metastasis to multiple organs].

    PubMed

    Kessoku, Hisashi; Yoshimura, Tsuyoshi; Iino, Takashi; Tanaka, Yasuhiro

    2014-01-01

    In January 2011, a 64-year-old woman who had undergone tumor resection for pleomorphic adenoma of the left parotid gland four times since her first operation in 1996 visited an orthopedist in our hospital complaining of pain in her right lower limb. Computed tomography (CT) of the whole body showed multiple tumors on the left parotid gland, right kidney, the sacrum, and both lungs. Biopsy of the sacral region and right nephrectomy were performed based on a clinical diagnosis of sacral and pulmonary metastases from renal cell carcinoma, and palliative radiation therapy was immediately begun on the sacral region. Given the definitive pathological diagnosis of metastasis of pleomorphic adenoma of the parotid gland, the recurrent tumor of the left parotid gland and the surrounding lymph nodes were first removed. Postoperative findings demonstrated that the pleomorphic adenoma had metastasized to the lymph nodes. The lung tumors were resected subsequently, and postoperative findings led to the diagnosis of pleomorphic adenoma. Metastasis of pleomorphic adenoma is known to be extremely rare, and to our knowledge this case of metastasis to a kidney is the first reported in Japan.

  18. Rabbit hematology.

    PubMed

    Marshall, Kemba L

    2008-09-01

    Using laboratory animal medicine as an established resource, companion animal veterinarians have access to many physiologic and basic science studies that we can now merge with our clinical impressions. By working with reference laboratories, companion animal veterinarians are poised to accelerate our knowledge of the normal rabbit rapidly. The aim of this article is to discuss normal hematopoiesis and infectious and metabolic diseases that specifically target the hemolymphatic system. Additionally, photographic representation of cell types is provided.

  19. US in preoperative evaluation of parotid gland neoplasms.

    PubMed

    Gerwel, Agata; Kosik, Krzysztof; Jurkiewicz, Dariusz

    2015-01-01

    Salivary gland neoplasms account for only 3% of all tumors of the head and neck area, but as they represent a wide variety of histological types, they are a big diagnostic challenge. The cornerstone of salivary gland neoplasm treatment, both for the benign and malignant lesions, is surgery. The main goal of the therapy is not only to achieve complete surgical tumor resection, but also to preserve adjacent structures (facial nerve, parapharyngeal space structures). Ultrasonography is an examination commonly used in the preoperative diagnosis of the lesions localized within salivary glands. Very often it is the only diagnostic imaging method used in these cases. The aim of the study was to establish diagnostic value of US examination and its parameters for the assessment of parotid gland tumors. A prospective study was performed on a group of 51 patients with parotid gland neoplasms, who over a period of 3 years underwent surgery in Otolaryngology and Laryngological Oncology Department with Craniomaxillofacial Surgery Department of Central Clinical Hospital of Ministry of Defence in Warsaw. All the included patients underwent US examination in the preoperative period. The parameters selected for the assessment were: ill-defined tumor margins, tumor vascularity and the presence of enlarged regional lymph nodes. The results of imaging examination were compared to the final diagnosis based on pathological examination of the surgical specimen. The parameters of the US examination such as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the evaluation of parotid gland tumors were established based on the examination results. An analysis was performed and ill-defined parotid tumor margins turned out to be a US parameter with higher diagnostic value for differentiating benign and malignant lesions than increased tumor vascularity. The presence of enlarged regional lymph nodes with blurred echostructure on the US examination

  20. Expression of claudin-5 in canine pancreatic acinar cell carcinoma - An immunohistochemical study.

    PubMed

    Jakab, Csaba; Rusvai, Miklós; Gálfi, Péter; Halász, Judit; Kulka, Janina

    2011-03-01

    Claudin-5 is an endothelium-specific tight junction protein. The aim of the present study was to detect the expression pattern of this molecule in intact pancreatic tissues and in well-differentiated and poorly differentiated pancreatic acinar cell carcinomas from dogs by the use of cross-reactive humanised anticlaudin-5 antibody. The necropsy samples taken from dogs included 10 nonneoplastic pancreatic tissues, 10 well-differentiated pancreatic acinar cell carcinomas, 10 poorly differentiated pancreatic acinar cell carcinomas, 5 intrahepatic metastases of well-differentiated and 5 intrahepatic metastases of poorly differentiated acinar cell carcinomas. A strong lateral membrane claudin-5 positivity was detected in exocrine cells in all intact pancreas samples. The endocrine cells of the islets of Langerhans and the epithelial cells of the ducts were negative for claudin-5. The endothelial cells of vessels and lymphatic channels in the stroma of the intact pancreas showed strong membrane positivity for this claudin. All well-differentiated exocrine pancreas carcinomas and all poorly-differentiated pancreatic acinar cell carcinoma samples showed a diffuse loss of claudin-5 expression. The claudin-5-positive peritumoural vessels and lymphatic channels facilitated the detection of vascular invasion of the claudin-5-negative cancer cells. In liver metastasis samples, the pancreatic carcinomas were negative for claudin-5. It seems that the loss of expression of claudin-5 may lead to carcinogenesis in canine exocrine pancreatic cells.

  1. The acinar differentiation determinant PTF1A inhibits initiation of pancreatic ductal adenocarcinoma

    PubMed Central

    Krah, Nathan M; De La O, Jean-Paul; Swift, Galvin H; Hoang, Chinh Q; Willet, Spencer G; Chen Pan, Fong; Cash, Gabriela M; Bronner, Mary P; Wright, Christopher VE; MacDonald, Raymond J; Murtaugh, L Charles

    2015-01-01

    Understanding the initiation and progression of pancreatic ductal adenocarcinoma (PDAC) may provide therapeutic strategies for this deadly disease. Recently, we and others made the surprising finding that PDAC and its preinvasive precursors, pancreatic intraepithelial neoplasia (PanIN), arise via reprogramming of mature acinar cells. We therefore hypothesized that the master regulator of acinar differentiation, PTF1A, could play a central role in suppressing PDAC initiation. In this study, we demonstrate that PTF1A expression is lost in both mouse and human PanINs, and that this downregulation is functionally imperative in mice for acinar reprogramming by oncogenic KRAS. Loss of Ptf1a alone is sufficient to induce acinar-to-ductal metaplasia, potentiate inflammation, and induce a KRAS-permissive, PDAC-like gene expression profile. As a result, Ptf1a-deficient acinar cells are dramatically sensitized to KRAS transformation, and reduced Ptf1a greatly accelerates development of invasive PDAC. Together, these data indicate that cell differentiation regulators constitute a new tumor suppressive mechanism in the pancreas. DOI: http://dx.doi.org/10.7554/eLife.07125.001 PMID:26151762

  2. Differentiation of pancreatic acinar carcinoma cells cultured on rat testicular seminiferous tubular basement membranes

    SciTech Connect

    Watanabe, T.K.; Hansen, L.J.; Reddy, N.K.; Kanwar, Y.S.; Reddy, J.K.

    1984-11-01

    The use of rat testicular seminiferous tubular basement membrane (STBM) segments as a model substratum for the in vitro maintenance of tumor cells dissociated from a transplantable pancreatic acinar rat carcinoma is described. Ultrastructurally pure, hollow tubular segments of STBM were prepared by mechanical disaggregation, DNase digestion, and deoxycholate treatment. Dissociated pancreatic acinar carcinoma cells adhered readily to STBM segments within 1 to 6 hr, and these STBM-tumor cell aggregates were maintained for up to 7 days in serum-free chemically defined medium supplemented with hydrocortisone, insulin, vitamin C, and soybean trypsin inhibitor. The tumor cells formed acinar-like clusters and displayed intercellular junctions and polarization of secretory granules toward the center of these clusters. By 4 days, virtually all cells of this acinar carcinoma maintained on STBM in supplemented chemically defined medium contained numerous secretory granules. Cell replication, as determined by (/sup 3/H)thymidine autoradiography, ceased within 18 hr of attachment of neoplastic cells to STBM; however, all cells incorporated (/sup 3/H)leucine as evidenced by light and electron microscopic autoradiography. In addition, two-dimensional analysis and fluorography of newly synthesized secretory proteins discharged by these cells in response to carbamylcholine revealed the presence of Mr 24,000 protein and 19 other secretory proteins characteristic of this tumor. The culture system utilizing STBM and supplemented chemically defined medium should allow investigation of the effects of a variety of factors on morphogenesis, cytodifferentiation, and gene expression in pancreatic acinar tumors.

  3. Total pancreatectomy for metachronous mixed acinar-ductal carcinoma in a remnant pancreas.

    PubMed

    Shonaka, Tatsuya; Inagaki, Mitsuhiro; Akabane, Hiromitsu; Yanagida, Naoyuki; Shomura, Hiroki; Yanagawa, Nobuyuki; Oikawa, Kensuke; Nakano, Shiro

    2014-09-07

    In October 2009, a 71-year-old female was diagnosed with a cystic tumor in the tail of the pancreas with an irregular dilatation of the main pancreatic duct in the body and tail of the pancreas. A distal pancreatectomy with splenectomy, and partial resection of the duodenum, jejunum and transverse colon was performed. In March 2011, a follow-up computed tomography scan showed a low density mass at the head of the remnant pancreas. We diagnosed it as a recurrence of the tumor and performed a total pancreatectomy for the remnant pancreas. In the histological evaluation of the resected specimen of the distal pancreas, the neoplastic cells formed an acinar and papillary structure that extended into the main pancreatic duct. Mucin5AC, α1-antitrypsin (α-AT) and carcinoembryonic antigen (CEA) were detected in the tumor cells by immunohistochemistry. In the resected head of the pancreas, the tumor was composed of both acinar and ductal elements with a mottled pattern. The proportions of each element were approximately 40% and 60%, respectively. Strongly positive α-AT cells were detected in the acinar element. Some tumor cells were also CEA positive. However, the staining for synaptophysin and chromogranin A was negative in the tumor cells. Ultimately, we diagnosed the tumor as a recurrence of mixed acinar-ductal carcinoma in the remnant pancreas. In conclusion, we report here a rare case of repeated pancreatic resection for multicentric lesions of mixed acinar-ductal carcinoma of the pancreas.

  4. Characterization of single potassium channels in mouse pancreatic acinar cells.

    PubMed Central

    Schmid, A; Schulz, I

    1995-01-01

    1. Single K(+)-selective channels with a conductance of about 48 pS (pipette, 145 mM KCl; bath, 140 mM NaCl + 4.7 mM KCl) were recorded in the patch-clamp whole-cell configuration in isolated mouse pancreatic acinar cells. 2. Neither application of the secretagogues acetylcholine (second messenger, inositol 1,4,5-trisphosphate) or secretin (second messenger, cAMP), nor addition of the catalytic subunit of protein kinase A to the pipette solution changed the activity of the 48 pS K+ channel. 3. Intracellular acidification with sodium propionate (20 mM) diminished activity of the 48 pS channel, whereas channel open probability was increased by cytosolic alkalization with 20 mM NH4Cl. 4. BaCl2 (5 mM), TEA (10 mM) or apamin (1 microM) added to the bath solution had no obvious effect on the kinetics of the 48 pS channel. Similarly, glibenclamide and diazoxide failed to influence the channel activity. 5. When extracellular NaCl was replaced by KCl, whole-cell recordings revealed an inwardly rectifying K+ current carried by a 17 pS K+ channel. 6. The inwardly rectifying K+ current was not pH dependent and could largely be blocked by Ba2+ but not by TEA. 7. Since the 48 pS K+ channel is neither Ca2+ nor cAMP regulated, we suggest that this channel could play a role in the maintenance of the negative cell resting potential. PMID:7623283

  5. Hyperglycemia simultaneously induces initial caries development and enhances spontaneous occlusal surface wear in molar teeth related to parotid gland disorder in alloxan-induced diabetic rats

    PubMed Central

    Nishimoto, Taiki; Kodama, Yasushi; Matsuura, Tetsuro; Ozaki, Kiyokazu; Taniguchi, Yoshihiko

    2016-01-01

    Diabetes and salivary gland dysfunction are major factors that induce dental caries in experimental animals, but there are no reports analyzing the association of dental caries and salivary glands in an animal model of diabetes mellitus (DM). To clarify the initial development of dental caries and preceding salivary gland disorder, we performed a histopathological analysis on teeth and salivary glands in diabetic Wistar rats 7 weeks after alloxan treatment (DM group) in comparison with nondiabetic rats (Non-DM group) and functional analysis on saliva secretion during the experimental period. Pilocarpine-induced salivary fluid secretion in diabetic rats gradually decreased with continuous hyperglycemia from immediately after alloxan treatment to the time of autopsy. Histopathologically, Oil Red O-positive lipid droplets accumulated in the acinar cells of the parotid gland. No tooth was stereoscopically defined as having dental caries in any of the rats in either group; however, the external appearance remarkably changed owing to occlusal wear in almost all molars in the DM group. The initial lesions of dental caries, appearing as micro-defects in dentin with bacterial colonization on the molar surface, were identified using histopathological analysis, and the incidence in the DM group was more than twice that in the Non-DM group. In conclusion, hyperglycemia simultaneously induces initial caries development and enhances spontaneous occlusal wear in molar teeth of Wistar rats 7 weeks after alloxan treatment. The parotid gland dysfunction caused by hyperglycemia may be mostly involved in the pathogenesis of occlusal wear as well as in dental caries in this diabetic model. PMID:28190924

  6. Simple tool for prediction of parotid gland sparing in intensity-modulated radiation therapy

    SciTech Connect

    Gensheimer, Michael F.; Hummel-Kramer, Sharon M.; Cain, David; Quang, Tony S.

    2015-10-01

    Sparing one or both parotid glands is a key goal when planning head and neck cancer radiation treatment. If the planning target volume (PTV) overlaps one or both parotid glands substantially, it may not be possible to achieve adequate gland sparing. This finding results in physicians revising their PTV contours after an intensity-modulated radiation therapy (IMRT) plan has been run and reduces workflow efficiency. We devised a simple formula for predicting mean parotid gland dose from the overlap of the parotid gland and isotropically expanded PTV contours. We tested the tool using 44 patients from 2 institutions and found agreement between predicted and actual parotid gland doses (mean absolute error = 5.3 Gy). This simple method could increase treatment planning efficiency by improving the chance that the first plan presented to the physician will have optimal parotid gland sparing.

  7. RABBIT POX

    PubMed Central

    Rosahn, Paul D.; Hu, Ch'uan-K'uei

    1935-01-01

    Observations on an epidemic of rabbit pox occurring in an isolated animal room during the winter of 1933–34 are reported. The clinical manifestations, consisting of a generalized papular eruption involving the skin and mucous membranes, together with blepharitis, ophthalmia, nasal discharge and lymphadenopathy were essentially similar to those noted in a pox epidemic of the previous year. This was true in general also of the pathological findings except that vacuolization, local necrosis and vesicle formation were seen in the epidermis, while in the previous year the microscopic pathology in the skin was confined to the corium. Evidence was presented indicating that the infection can be transmitted through the medium of a personal carrier, and that transmission in this manner can occur during the incubation period or before a definite diagnosis is possible. The findings also demonstrated that the etiological agents responsible for the disease reported here and that of the previous year were immunologically related, and that the immunity in recovered animals effectively persisted during the entire period for which data are available, 9 to 12 months. It appeared also that young animals suckling an immune doe were more refractory to the development of the lesions of rabbit pox than were the young of susceptible does. PMID:19870418

  8. SERUM AND PAROTID FLUIS UREA-LEVELS IN UNREALOADED HEALTHY YOUNG ADULTS

    DTIC Science & Technology

    Forty-four healthy young adult male subjects were given oral doses of urea, and parotid fluid and serum urea levels were studied for 1 to 3 hours. A...highly significant correlation between urea in serum and in parotid fluid (r equals 0.982) was found. The indication was that, with flow rate...carefully controlled, parotid fluid could be used interchangeably with serum in urea determination, regardless of the magnitude of the blood concentration. (Author)

  9. Combination of Hot-Hypertonic Saline and Pressure Dressing in the Management of Parotid Fistula.

    PubMed

    Aisha; Fatima, Saira; Memon, Aijaz Ahmed

    2015-12-01

    Parotid fistula is a rare complication of surgical or non-surgical trauma on or in the vicinity of parotid gland. Many pharmacological agents and surgical methods are used to treat it with their own merits, demerits and patient preferences. Injection of hypertonic hot saline along with compression dressing is an economical, patient-preferred and almost complication-free method to deal parotid fistula with promising results.

  10. Simultaneous Bilateral Hypertrophies of the Parotid Gland and Masseter Muscle: Case Report.

    PubMed

    Prabhu, Rohan; Mandel, Louis

    2017-01-01

    Increased salivary demand can lead to enlarged parotid salivary glands, and increased activity of the masseter muscles can cause masseter hypertrophy. This report describes a most unusual case of simultaneous bilateral hypertrophies of the parotid gland and masseter muscle originating from the very extensive habit of chewing gum. An extensive literature review uncovered many cases of the independent existence of masseteric or parotid hypertrophy, but no example of the simultaneous occurrence of these 2 conditions.

  11. Unusual Foreign Body of Parotid Gland Presenting as Sialolithiasis: Case Report and Literature Review

    PubMed Central

    Sreetharan, Sivapatha Sundaram; Philip, Rajan

    2012-01-01

    This case report highlights an unusual case where a foreign body in the parotid gland was initially thought to be sialolithiasis based on CT scans. The foreign body was safely retrieved from the parotid gland without formal superficial parotidectomy using methylene blue and an image intensifier to localize the lesion. Diagnosis and management of foreign bodies in the parotid gland are reviewed, and surgical options in removal of such lesions are discussed. PMID:23320231

  12. Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia

    NASA Astrophysics Data System (ADS)

    Liou, Geou-Yarh; Döppler, Heike; Braun, Ursula B.; Panayiotou, Richard; Scotti Buzhardt, Michele; Radisky, Derek C.; Crawford, Howard C.; Fields, Alan P.; Murray, Nicole R.; Wang, Q. Jane; Leitges, Michael; Storz, Peter

    2015-02-01

    The transdifferentiation of pancreatic acinar cells to a ductal phenotype (acinar-to-ductal metaplasia, ADM) occurs after injury or inflammation of the pancreas and is a reversible process. However, in the presence of activating Kras mutations or persistent epidermal growth factor receptor (EGF-R) signalling, cells that underwent ADM can progress to pancreatic intraepithelial neoplasia (PanIN) and eventually pancreatic cancer. In transgenic animal models, ADM and PanINs are initiated by high-affinity ligands for EGF-R or activating Kras mutations, but the underlying signalling mechanisms are not well understood. Here, using a conditional knockout approach, we show that protein kinase D1 (PKD1) is sufficient to drive the reprogramming process to a ductal phenotype and progression to PanINs. Moreover, using 3D explant culture of primary pancreatic acinar cells, we show that PKD1 acts downstream of TGFα and Kras, to mediate formation of ductal structures through activation of the Notch pathway.

  13. Effect of taurine on acinar cell apoptosis and pancreatic fibrosis in dibutyltin dichloride-induced chronic pancreatitis.

    PubMed

    Matsushita, Koki; Mizushima, Takaaki; Shirahige, Akinori; Tanioka, Hiroaki; Sawa, Kiminari; Ochi, Koji; Tanimoto, Mitsune; Koide, Norio

    2012-01-01

    The relationship between pancreatic fibrosis and apoptosis of pancreatic acinar cells has not been fully elucidated. We reported that taurine had an anti-fibrotic effect in a dibutyltin dichloride (DBTC)-chronic pancreatitis model. However, the effect of taurine on apoptosis of pancreatic acinar cells is still unclear. Therefore, we examined apoptosis in DBTC-chronic pancreatitis and in the AR42J pancreatic acinar cell line with/without taurine. Pancreatic fibrosis was induced by a single administration of DBTC. Rats were fed a taurine-containing diet or a normal diet and were sacrificed at day 5. The AR42J pancreatic acinar cell line was incubated with/without DBTC with taurine chloramines. Apoptosis was determined by using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay. The expression of Bad and Bcl-2 proteins in the AR42J cells lysates was detected by Western blot analysis. The apoptotic index of pancreatic acinar cells in DBTC-administered rats was significantly increased. Taurine treatment inhibited pancreatic fibrosis and apoptosis of acinar cells induced by DBTC. The number of TUNEL-positive cells in the AR42J pancreatic acinar cell lines was significantly increased by the addition of DBTC. Incubation with taurine chloramines ameliorated these changes. In conclusion, taurine inhibits apoptosis of pancreatic acinar cells and pancreatitis in experimental chronic pancreatitis.

  14. Pancreatic acinar cells-derived cyclophilin A promotes pancreatic damage by activating NF-κB pathway in experimental pancreatitis

    SciTech Connect

    Yu, Ge; Wan, Rong; Hu, Yanling; Ni, Jianbo; Yin, Guojian; Xing, Miao; Shen, Jie; Tang, Maochun; Chen, Congying; Fan, Yuting; Xiao, Wenqin; Zhao, Yan; Wang, Xingpeng; and others

    2014-01-31

    Highlights: • CypA is upregulated in experimental pancreatitis. • CCK induces expression and release of CypA in acinar cell in vitro. • rCypA aggravates CCK-induced acinar cell death and inflammatory cytokine production. • rCypA activates the NF-κB pathway in acinar cells in vitro. - Abstract: Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration of sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-κB p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-κB pathway.

  15. Papillary Cystadenocarcinoma of the Parotid Gland: A Rare Case Report.

    PubMed

    Telugu, Ramesh Babu; Job, Anjana Juanita; Manipadam, Marie Therese

    2016-06-01

    Papillary cystadenocarcinoma is a rare malignant neoplasm of the salivary gland, characterized by noticeable cystic and solid areas with papillary endophytic projections. These tumours lack features that characterize cystic variants of several more common salivary gland carcinomas. It was first described in 1991 by World Health Organization as a separate entity and cystadenocarcinoma with or without papillary component in the AFIP classification. Most of these tumours occurred in the major salivary glands followed by minor salivary glands. Cystadenocarcinoma is the malignant counterpart of cystadenoma. We report a case of papillary cystadenocarcinoma of parotid. A 40-year-old lady presented with gradually progressive swelling below the right ear associated with occasional pain. Clinical and radiological features suggested benign neoplasm. Right lobe superficial parotidectomy was performed. The histopathologic diagnosis showed papillary cystadenocarinoma of the parotid gland. Histologic confirmation of stromal invasion is required to differentiate it from the benign lesion. Conservative wide local surgical excision is the treatment of choice.

  16. Papillary Cystadenocarcinoma of the Parotid Gland: A Rare Case Report

    PubMed Central

    Job, Anjana Juanita; Manipadam, Marie Therese

    2016-01-01

    Papillary cystadenocarcinoma is a rare malignant neoplasm of the salivary gland, characterized by noticeable cystic and solid areas with papillary endophytic projections. These tumours lack features that characterize cystic variants of several more common salivary gland carcinomas. It was first described in 1991 by World Health Organization as a separate entity and cystadenocarcinoma with or without papillary component in the AFIP classification. Most of these tumours occurred in the major salivary glands followed by minor salivary glands. Cystadenocarcinoma is the malignant counterpart of cystadenoma. We report a case of papillary cystadenocarcinoma of parotid. A 40-year-old lady presented with gradually progressive swelling below the right ear associated with occasional pain. Clinical and radiological features suggested benign neoplasm. Right lobe superficial parotidectomy was performed. The histopathologic diagnosis showed papillary cystadenocarinoma of the parotid gland. Histologic confirmation of stromal invasion is required to differentiate it from the benign lesion. Conservative wide local surgical excision is the treatment of choice. PMID:27504297

  17. Metachronous bilateral pleomorphic adenoma of the parotid gland.

    PubMed

    Silva, Sindeval José da; Costa Junior, Gabriel Tadeu; Brant Filho, Adalberto Caldeira; Faria, Paulo Rogério; Loyola, Adriano Mota

    2006-03-01

    Bilateral salivary gland tumors are very rare, accounting for 3% of all parotid gland tumors. Although the most common tumor with bilateral development is the Warthin tumor, pleomorphic adenomas (PA) have been diagnosed simultaneously as well, but in a smaller incidence. Because of this, the prevalence, etiology, pathogenesis, and behavior of the PA in this context are poorly understood. We present a case of bilateral metachronous PA affecting the parotid gland in a 63-year-old woman. Clinically, the lesions presented with similar aspects as seen in cases of solitary PA with slow-growing asymptomatic nodule. Both lesions were diagnosed by fine-needle aspiration biopsy at an interval of 2 years between them. A total and superficial parotidectomy for left and right tumors, respectively, was performed. Only on the left side some facial nerve branches were removed that induced partial paralysis in the patient. A review of the pertinent literature is included.

  18. Parotid tail pleomorphic adenoma extending to the parapharyngeal space.

    PubMed

    Polat, Kerem; Doğan, Mansur; Yüce, Salim; Uysal, Ismail Önder; Müderris, Suphi

    2013-03-01

    Parapharyngeal space tumors are rare, accounting for 0.5% of head and neck neoplasms. Most of them are benign and originate in the salivary glands, especially the pleomorphic adenoma. We presented a 47-year-old man with parotid tail pleomorphic adenoma extending to the parapharyngeal space. The patient applied to our clinic with the complaints of a painless mass on his neck and in his mouth for 3 months. After fine needle aspiration biopsy, the mass was diagnosed as pleomorphic adenoma. The patient was hospitalized and operated in our clinic. As we see in literature review, parapharyngeal space tumors are rare, and most of them are pleomorphic adenomas arising from the deep lobe of the parotid gland and extend into the PPS.

  19. Role of parotid amylase in starch digestion in the gastro-intestinal tracts of diabetic rats.

    PubMed

    Kurahashi, M; Inomata, K

    1989-09-01

    In order for the role of parotid amylase in starch digestion in the gastro-intestinal tracts of diabetic rats to be clarified, this study investigated the effect of parotid-duct ligation on both amylase secretion from the parotid glands and pancreas into the gastro-intestinal tract and on starch digestion in the gastro-intestinal contents during feedings. In both diabetic rats and control rats, parotid-duct ligation reduced amylase activity in both the parotid glands during fasting and in the gastric contents after feeding. The amylase activity in the intestinal contents after feeding was reduced by parotid-duct ligation in the diabetic rats. Starch digestion in the gastro-intestinal tract after feeding was reduced by parotid-duct ligation in the diabetic rats. The results suggest that most of the amylase activity in the gastric contents and a large part of the amylase activity in the intestinal contents are derived from the parotid glands, and that parotid amylase plays an important role in starch digestion in the gastro-intestinal tracts of diabetic rats.

  20. Study of Preoperative Predictive Signs in Management of Facial Nerve in Parotid Tumors

    PubMed Central

    CHIRILA, Magdalena; MURESAN, Mihaela; BOLBOACA, Sorana D.

    2014-01-01

    Objectives: To find preoperative predictive signs for better surgical planning of the facial nerve in parotid tumors. Methods: Prospective study in patients with primary parotid malignancies. Patients with primary parotid malignant tumor were investigated for preoperative clinical signs in correlation with histological findings and surgical management of the facial nerve. Outcomes: The study included 47 patients. Several clinical findings as facial pain, paresthesia, and rapid growth of tumor might suggest the risk of malignancy. Paresis/palsy of the facial nerve was correlates with direct neural involvement. Conclusion: There are several predictive clinical signs that might suggest malignancy of a parotid tumor. PMID:25553124

  1. [Flow rate, amylase and protein content of parotid saliva in sialadenosis (author's transl)].

    PubMed

    Chilla, R; Opaitz, M; Arglebe, C

    1978-03-01

    Flow rate, protein concentration and amylase activity of parotid saliva were investigated in 17 patients with sialadenosis. The results were compared with the data obtained from 90 healthy controls. Total protein and amylase concentrations of saliva did not change although, under the influence of sialadenosis, the parotid gland clearly shows ultrastructural signs of disturbed protein secretion. Also the flow rates of parotid saliva were the same in sialadenosis patients and the control group. This can be explained by the patho-physiology of parotid secretion from the sialadenotic gland.

  2. Acute neonatal parotid abscess: A rare case report

    PubMed Central

    Kolekar, Shreesh; Chincholi, Tejas S.; Kshirsagar, Ashok; Porwal, Narendra

    2016-01-01

    Acute suppurative parotitis is uncommon in children and is very rare in neonates. Most common organism isolated is Staphylococcus aureus. We present a 15-day-old full-term breast-fed female neonate with left-sided acute parotid abscess. The baby presented with a left preauricular swelling, pain and redness. Pus was exuded from left Stensen's duct on compression of the gland externally. Early diagnosis and proper intravenous antibiotics are the keys to the treatment. PMID:28051052

  3. [2 cases of adenolymphoma of the parotid gland].

    PubMed

    Andreini, A; Avogadro, M; Trassini, R

    1979-01-01

    Starting from two cases of adenolymphoma of the parotid gland they had under observation, the Authors underline their doubts regarding the histogenesis, discuss the clinical approach and show their attitude towards the therapy. It consists of an enucleation or nucleoresection of the tumour in case only the superficial part of the gland is affected; a total parotidectomy with facial nerve preservation and without any radiotherapy, in case of a radical operation; with complementary radiotherapy if the operation has not been radical for certain.

  4. In vivo biocompatibility of the PLGA microparticles in parotid gland

    PubMed Central

    Cantín, Mario; Miranda, Patricio; Suazo Galdames, Iván; Zavando, Daniela; Arenas, Patricia; Velásquez, Luis; Vilos, Cristian

    2013-01-01

    Poly(lactic-co-glycolic acid) (PLGA) microparticles are used in various disorders for the controlled or sustained release of drugs, with the management of salivary gland pathologies possible using this technology. There is no record of the response to such microparticles in the glandular parenchyma. The purpose of this study was to assess the morphological changes in the parotid gland when injected with a single dose of PLGA microparticles. We used 12 adult female Sprague Dawley rats (Rattus norvegicus) that were injected into their right parotid gland with sterile vehicle solution (G1, n=4), 0.5 mg PLGA microparticles (G2, n=4), and 0.75 mg PLGA microparticles (G3, n=4); the microparticles were dissolved in a sterile vehicle solution. The intercalar and striated ducts lumen, the thickness of the acini and the histology aspect in terms of the parenchyma organization, cell morphology of acini and duct system, the presence of polymeric residues, and inflammatory response were determined at 14 days post-injection. The administration of the compound in a single dose modified some of the morphometric parameters of parenchyma (intercalar duct lumen and thickness of the glandular acini) but did not induce tissue inflammatory response, despite the visible presence of polymer waste. This suggests that PLGA microparticles are biocompatible with the parotid tissue, making it possible to use intraglandular controlled drug administration. PMID:24228103

  5. Outcomes of temporal bone resection for locally advanced parotid cancer.

    PubMed

    Mehra, Saral; Morris, Luc G; Shah, Jatin; Bilsky, Mark; Selesnick, Samuel; Kraus, Dennis H

    2011-11-01

    This study was conducted to report outcomes and identify factors predictive of survival and recurrence in patients undergoing lateral temporal bone resection (LTBR) as part of an extended radical parotidectomy for parotid cancer. This is a retrospective cohort study which includes all patients undergoing LTBR for parotid cancer between 1994 and 2010 at two affiliated academic centers. Survival and recurrence rates were analyzed using the Kaplan-Meier method and Cox multivariate regression. A total of 12 patients with median follow-up duration of 30.6 months were included: 6 de novo cases and 6 patients referred after local recurrence. Actuarial locoregional control at 2 years was 73%. Most patients (11; 92%) developed disease recurrence with distant metastases the most common site of first failure (83%). Overall and disease-specific survival rates were 80% at 2 years and 22.5% at 5 years. Recurrence-free survival (RFS) was 67% at 2 years and 8.3% at 5 years. On multivariate analysis, surgical margin status was an independent predictor of RFS (hazard ratio = 3.85, p = 0.045). In advanced parotid cancer, LTBR with a goal of gross total resection offers good locoregional control with an acceptable complication rate. The benefits of this surgery must be balanced with the morbidity and low likelihood of long-term survival, with most patients ultimately experiencing disease recurrence and death.

  6. Outcomes of Temporal Bone Resection for Locally Advanced Parotid Cancer

    PubMed Central

    Mehra, Saral; Morris, Luc G.; Shah, Jatin; Bilsky, Mark; Selesnick, Samuel; Kraus, Dennis H.

    2011-01-01

    This study was conducted to report outcomes and identify factors predictive of survival and recurrence in patients undergoing lateral temporal bone resection (LTBR) as part of an extended radical parotidectomy for parotid cancer. This is a retrospective cohort study which includes all patients undergoing LTBR for parotid cancer between 1994 and 2010 at two affiliated academic centers. Survival and recurrence rates were analyzed using the Kaplan-Meier method and Cox multivariate regression. A total of 12 patients with median follow-up duration of 30.6 months were included: 6 de novo cases and 6 patients referred after local recurrence. Actuarial locoregional control at 2 years was 73%. Most patients (11; 92%) developed disease recurrence with distant metastases the most common site of first failure (83%). Overall and disease-specific survival rates were 80% at 2 years and 22.5% at 5 years. Recurrence-free survival (RFS) was 67% at 2 years and 8.3% at 5 years. On multivariate analysis, surgical margin status was an independent predictor of RFS (hazard ratio = 3.85, p = 0.045). In advanced parotid cancer, LTBR with a goal of gross total resection offers good locoregional control with an acceptable complication rate. The benefits of this surgery must be balanced with the morbidity and low likelihood of long-term survival, with most patients ultimately experiencing disease recurrence and death. PMID:22547966

  7. SMAS fold flap and ADM repair of the parotid bed following removal of parotid haemangiomas via pre- and retroauricular incisions to improve cosmetic outcome and prevent Frey's syndrome.

    PubMed

    Chen, Weiliang; Li, Jingsong; Yang, Zhaohui; Yongjie, Wang; Zhiquan, Wang; Wang, Youyuan

    2008-08-01

    The growth of parotid haemangiomas during the proliferative phase may be rapid and unpredictable. Involution often takes many years, with attendant psychological sequelae to the child. Although conservative management is usually proposed for parotid haemangiomas occurring in infancy, this may not be particularly helpful and the haemangioma difficult to conceal. The purpose of this study was to evaluate the reliable and aesthetic benefit of using a superficial musculoaponeurotic system (SMAS) fold flap and allograft dermal matrix (ADM) repair of the parotid bed following parotid haemangiomas via pre- and retroauricular incision. Forty-three paediatric patients (33 boys and 10 girls) with haemangiomas involving the parotid gland underwent total parotidectomy using a pre- and retroauricular approach with intraoperative placement of ADM within the parotid bed. They further underwent repair of the parotid bed with SMAS fold flaps. A panel of three plastic surgeons assessed the cosmetic outcomes. All of the patients were evaluated using a short questionnaire; postoperative gustatory sweating was assessed using a modification of Minor's starch-iodine test.

  8. [Distant metastases to the parotid gland--review of the literature and report of own two cases].

    PubMed

    Markowski, Jarosław; Gierek, Tatiana; Zielińska-Pajak, Ewa; Witkowska, Małgorzata; Wodołazski, Anatol; Pajak, Jacek; Paluch, Jarosław

    2005-01-01

    Metastatic tumors to the parotid gland are very uncommon and it accounts for 8% of all cancers of parotid gland. The parotid gland and its lymph nodes are possible sites of metastases from head and neck cancers. However, metastasis from distant primary neoplasm below clavicle is possible, too. The authors presented the two cases of distant metastases to the parotid gland. The women with breast cancer and metastases to the parotid gland 11 years after surgery, radio- and chemotherapy of breast cancer. She died 7 months after parotid surgery of systemically advanced disease. The man with metastasis of malignant melanoma of unknown primary site. He underwent total parotid surgery with the tumor and lymph nodes. He died 7 months after surgery. In spite of intensive exam the primary location of the melanoma was unknown. The authors described pathophysiology of distant metastases to the parotid gland with special attention to possibilities of treatment and survival.

  9. Direct Imaging of RAB27B-Enriched Secretory Vesicle Biogenesis in Lacrimal Acinar Cells Reveals Origins on a Nascent Vesicle Budding Site

    PubMed Central

    Chiang, Lilian; Karvar, Serhan; Hamm-Alvarez, Sarah F.

    2012-01-01

    This study uses YFP-tagged Rab27b expression in rabbit lacrimal gland acinar cells, which are polarized secretory epithelial cells, to characterize early stages of secretory vesicle trafficking. Here we demonstrate the utility of YFP-Rab27b to delineate new perspectives on the mechanisms of early vesicle biogenesis in lacrimal gland acinar cells, where information is significantly limited. Protocols were developed to deplete the mature YFP-Rab27b-enriched secretory vesicle pool in the subapical region of the cell, and confocal fluorescence microscopy was used to track vesicle replenishment. This analysis revealed a basally-localized organelle, which we termed the “nascent vesicle site,” from which nascent vesicles appeared to emerge. Subapical vesicular YFP-Rab27b was co-localized with p150Glued, a component of the dynactin cofactor of cytoplasmic dynein. Treatment with the microtubule-targeted agent, nocodazole, did not affect release of mature secretory vesicles, although during vesicle repletion it significantly altered nascent YFP-Rab27b-enriched secretory vesicle localization. Instead of moving to the subapical region, these vesicles were trapped at the nascent vesicle site which was adjacent to, if not a sub-compartment of, the trans-Golgi network. Finally, YFP-Rab27b-enriched secretory vesicles which reached the subapical cytoplasm appeared to acquire the actin-based motor protein, Myosin 5C. Our findings show that Rab27b enrichment occurs early in secretory vesicle formation, that secretory vesicles bud from a visually discernable nascent vesicle site, and that transport from the nascent vesicle site to the subapical region requires intact microtubules. PMID:22363735

  10. Acinar autolysis and mucous extravasation in human sublingual glands: a microscopic postmortem study

    PubMed Central

    AZEVEDO-ALANIS, Luciana Reis; TOLENTINO, Elen de Souza; de ASSIS, Gerson Francisco; CESTARI, Tânia Mary; LARA, Vanessa Soares; DAMANTE, José Humberto

    2015-01-01

    Although some morphological investigations on aged human sublingual glands (HSG) found eventual phenomena identified as autolysis and mucous extravasation, the exact meaning of these findings has not been elucidated. Objective The aim of this work is to investigate whether acinar autolysis and mucous extravasation are related to the aging process in human sublingual glands. We also speculate if autolytic changes may assist forensic pathologists in determining time of death. Material and Methods 186 cadavers’ glands were allocated to age groups: I (0–30 years); II (31–60), and III (61–90). Time and mode of death were also recorded. Acinar autolysis and mucous extravasation were classified as present or absent. Ultrastructural analysis was performed using transmission electron microscopy (TEM). Data were compared using Mann-Whitney U, Spearman’s correlation coefficient, Kruskal-Wallis, and Dunn tests (p<0.05). Results There was correlation between age and acinar autolysis (r=0.38; p=0.0001). However, there was no correlation between autolysis and time of death. No differences were observed between genders. TEM showed mucous and serous cells presenting nuclear and membrane alterations and mucous cells were more susceptible to autolysis. Conclusion Acinar autolysis occurred in all age groups and increased with age while mucous extravasation was rarely found. Both findings are independent. Autolysis degrees in HSG could not be used to determine time of death. PMID:26537715

  11. Snail1 is required for the maintenance of the pancreatic acinar phenotype

    PubMed Central

    Loubat-Casanovas, Jordina; Peña, Raúl; Gonzàlez, Núria; Alba-Castellón, Lorena; Rosell, Santi; Francí, Clara; Navarro, Pilar; de Herreros, Antonio García

    2016-01-01

    The Snail1 transcriptional factor is required for correct embryonic development, yet its expression in adult animals is very limited and its functional roles are not evident. We have now conditionally inactivated Snail1 in adult mice and analyzed the phenotype of these animals. Snail1 ablation rapidly altered pancreas structure: one month after Snail1 depletion, acinar cells were markedly depleted, and pancreas accumulated adipose tissue. Snail1 expression was not detected in the epithelium but was in pancreatic mesenchymal cells (PMCs). Snail1 ablation in cultured PMCs downregulated the expression of several β-catenin/Tcf-4 target genes, modified the secretome of these cells and decreased their ability to maintain acinar markers in cultured pancreas cells. Finally, Snail1 deficiency modified the phenotype of pancreatic tumors generated in transgenic mice expressing c-myc under the control of the elastase promoter. Specifically, Snail1 depletion did not significantly alter the size of the tumors but accelerated acinar-ductal metaplasia. These results demonstrate that Snail1 is expressed in PMCs and plays a pivotal role in maintaining acinar cells within the pancreas in normal and pathological conditions. PMID:26735179

  12. Pancreatic (acinar) metaplasia of the gastric mucosa. Histology, ultrastructure, immunocytochemistry, and clinicopathologic correlations of 101 cases.

    PubMed

    Doglioni, C; Laurino, L; Dei Tos, A P; De Boni, M; Franzin, G; Braidotti, P; Viale, G

    1993-11-01

    The occasional finding within the gastric mucosa of unidentified epithelial cells with morphological features closely resembling those of pancreatic acinar cells has prompted us to investigate a retrospective series of 8,430 consecutive gastric biopsies and of 126 surgical specimens of gastric resection and total gastrectomy. The aims of the study were to morphologically and immunocytochemically characterize these cells, to define their actual prevalence in a large series of unselected cases, and to assess the clinicopathologic correlates of their occurrence. Pancreatic acinar-like cells characterized by abundant cytoplasm, which was acidophilic and finely granular in the apical and middle portions and basophilic in the basal compartment, have been identified in 101 cases (84 gastric biopsies and 17 gastrectomies). These cells, arranged in nests or in variably sized lobules among the gastric glands, were morphologically indistinguishable from pancreatic acinar cells, both by light and by electron microscopy. Furthermore, they were consistently immunoreactive for pancreatic lipase and trypsinogen and, in 75% of the cases, for pancreatic alpha-amylase. The appearance of these cells within the gastric mucosa was correlated significantly with chronic gastritis (p = 0.032) and with the simultaneous occurrence of intestinal and pyloric types of gastric metaplasia (p = 0.021). The findings indicate that this is a previously unrecognized pancreatic (acinar) metaplasia of the gastric mucosa, clinically and morphologically distinct from pancreatic heterotopia.

  13. Aspirin Protects against Acinar Cells Necrosis in Severe Acute Pancreatitis in Mice

    PubMed Central

    Lu, Guotao; Tong, Zhihui; Ding, Yanbing; Liu, Jinjiao; Pan, Yiyuan; Gao, Lin; Tu, Jianfeng; Liu, George

    2016-01-01

    Aspirin has a clear anti-inflammatory effect and is used as an anti-inflammatory agent for both acute and long-term inflammation. Previous study has indicated that aspirin alleviated acute pancreatitis induced by caerulein in rat. However, the role of aspirin on severe acute pancreatitis (SAP) and the necrosis of pancreatic acinar cell are not yet clear. The aim of this study was to determine the effects of aspirin treatment on a SAP model induced by caerulein combined with Lipopolysaccharide. We found that aspirin reduced serum amylase and lipase levels, decreased the MPO activity, and alleviated the histopathological manifestations of pancreas and pancreatitis-associated lung injury. Proinflammatory cytokines were decreased and the expression of NF-κB p65 in acinar cell nuclei was suppressed after aspirin treatment. Furthermore, aspirin induced the apoptosis of acinar cells by TUNEL assay, and the expression of Bax and caspase 3 was increased and the expression of Bcl-2 was decreased. Intriguingly, the downregulation of critical necrosis associated proteins RIP1, RIP3, and p-MLKL was observed; what is more, we additionally found that aspirin reduced the COX level of pancreatic tissue. In conclusion, our data showed that aspirin could protect pancreatic acinar cell against necrosis and reduce the severity of SAP. Clinically, aspirin may potentially be a therapeutic intervention for SAP. PMID:28119929

  14. Neurogenin 3-directed cre deletion of Tsc1 gene causes pancreatic acinar carcinoma.

    PubMed

    Ding, Li; Han, Lingling; Li, Yin; Zhao, Jing; He, Ping; Zhang, Weizhen

    2014-11-01

    The role of tuberous sclerosis complex (TSC) in the pathogenesis of pancreatic cancers remains largely unknown. The present study shows that neurogenin 3 directed Cre deletion of Tsc1 gene induces the development of pancreatic acinar carcinoma. By cross-breeding the Neurog3-cre mice with Tsc1 (loxp/loxp) mice, we generated the Neurog3-Tsc1-/- transgenic mice in which Tsc1 gene is deleted and mTOR signaling activated in the pancreatic progenitor cells. All Neurog3-Tsc1-/- mice developed notable adenocarcinoma-like lesions in pancreas starting from the age of 100 days old. The tumor lesions are composed of cells with morphological and molecular resemblance to acinar cells. Metastasis of neoplasm to liver and lung was detected in 5% of animals. Inhibition of mTOR signaling by rapamycin significantly attenuated the growth of the neoplasm. Relapse of the neoplasm occurred within 14 days upon cessation of rapamycin treatment. Our studies indicate that activation of mTOR signaling in the pancreatic progenitor cells may trigger the development of acinar carcinoma. Thus, mTOR may serve as a potential target for treatment of pancreatic acinar carcinoma.

  15. Imaging findings in a case of mixed acinar-endocrine carcinoma of the pancreas.

    PubMed

    Chung, Won Jung; Byun, Jae Ho; Lee, Seung Soo; Lee, Moon-Gyu

    2010-01-01

    Mixed acinar-endocrine carcinoma (MAEC) of the pancreas is extremely uncommon. We report here a rare case of MAEC of the pancreas presenting as watery diarrhea. This is the first report in the English-language literature that describes the imaging findings of MAEC of the pancreas, including computed tomography (CT), magnetic resonance (MR) imaging, and MR cholangiopancreatography features.

  16. Characterization of a novel model of pancreatic fibrosis and acinar atrophy.

    PubMed

    Murayama, K M; Barent, B L; Gruber, M; Brooks, A; Eliason, S; Brunt, E M; Smith, G S

    1999-01-01

    Significant fibrosis and acinar atrophy are characteristics of chronic pancreatitis; however, because of the lack of a reproducible model, early phases of these changes are poorly understood. We have developed a model of severe hyperstimulation and obstruction pancreatitis (SHOP) to better define the mechanisms of early pancreatic fibrogenesis. Sprague-Dawley rats were used and SHOP was induced by complete pancreatic duct obstruction and daily cerulein hyperstimulation (50 microg/kg intraperitoneally). Animals were killed at 24, 48, 72, and 96 hours. Control animals underwent sham operation and received no cerulein. Pancreata were prepared for hematoxylin and eosin and sirius red (collagen-specific) staining and for hydroxyproline assay (measure of total collagen content). We found moderate amounts of edema and inflammation but minimal parenchymal necrosis. Significant loss of acinar cell mass was noted by 48 hours, and normal acinar cells were essentially absent by 96 hours. Tissue collagen content increased with time and large amounts of interstitial collagen were detected by 72 hours. In conclusion, SHOP is a novel model of early pancreatic fibrosis associated with minimal necrosis and a significant decrease in acinar cell mass, making it an ideal model to study the early cellular mechanisms of pancreatic fibrogenesis.

  17. Bilateral parotid enlargement as a presenting feature of bulimia nervosa in a post-adolescent male.

    PubMed Central

    Buchanan, J. A.; Fortune, F.

    1994-01-01

    An unusual case of bulimia nervosa in a post-adolescent male is reported. The clinical presentation was one of painless parotid swelling of 3 years duration with marked weight loss and underlying metabolic alkalosis. The diagnostic significance of parotid salivary gland swellings is discussed. Images Figure 1 Figure 2 PMID:8140014

  18. Use of semiconducting laser in drug-induced chronic bilateral inflammation of parotid glands

    NASA Astrophysics Data System (ADS)

    Grzesiak-Janas, Grazyna

    1997-10-01

    A case of chronic bilateral inflammation of parotid glands in a patient as a results of complication induced by the drug Ospolot in the treatment of epilepsy was presented. Apart from conventional methods a semiconducting laser was used. The laser beam had beneficial effect on elimination of pain and increase in the parotid gland secretion activity.

  19. An intraoperative diagnosis of parotid gland tumors using Raman spectroscopy and support vector machine

    NASA Astrophysics Data System (ADS)

    Yan, Bing; Wen, Zhining; Li, Yi; Li, Longjiang; Xue, Lili

    2014-11-01

    The preoperative and intraoperative diagnosis of parotid gland tumors is difficult, but is important for their surgical management. In order to explore an intraoperative diagnostic method, Raman spectroscopy is applied to detect the normal parotid gland and tumors, including pleomorphic adenoma, Warthin’s tumor and mucoepidermoid carcinoma. In the 600-1800 cm-1 region of the Raman shift, there are numerous spectral differences between the parotid gland and tumors. Compared with Raman spectra of the normal parotid gland, the Raman spectra of parotid tumors show an increase of the peaks assigned to nucleic acids and proteins, but a decrease of the peaks related to lipids. Spectral differences also exist between the spectra of parotid tumors. Based on these differences, a remarkable classification and diagnosis of the parotid gland and tumors are carried out by support vector machine (SVM), with high accuracy (96.7~100%), sensitivity (93.3~100%) and specificity (96.7~100%). Raman spectroscopy combined with SVM has a great potential to aid the intraoperative diagnosis of parotid tumors and could provide an accurate and rapid diagnostic approach.

  20. Viral infections of rabbits.

    PubMed

    Kerr, Peter J; Donnelly, Thomas M

    2013-05-01

    Viral diseases of rabbits have been used historically to study oncogenesis (e.g. rabbit fibroma virus, cottontail rabbit papillomavirus) and biologically to control feral rabbit populations (e.g. myxoma virus). However, clinicians seeing pet rabbits in North America infrequently encounter viral diseases although myxomatosis may be seen occasionally. The situation is different in Europe and Australia, where myxomatosis and rabbit hemorrhagic disease are endemic. Advances in epidemiology and virology have led to detection of other lapine viruses that are now recognized as agents of emerging infectious diseases. Rabbit caliciviruses, related to rabbit hemorrhagic disease, are generally avirulent, but lethal variants are being identified in Europe and North America. Enteric viruses including lapine rotavirus, rabbit enteric coronavirus and rabbit astrovirus are being acknowledged as contributors to the multifactorial enteritis complex of juvenile rabbits. Three avirulent leporid herpesviruses are found in domestic rabbits. A fourth highly pathogenic virus designated leporid herpesvirus 4 has been described in Canada and Alaska. This review considers viruses affecting rabbits by their clinical significance. Viruses of major and minor clinical significance are described, and viruses of laboratory significance are mentioned.

  1. Acinar Cell Apoptosis in Serpini2-Deficient Mice Models Pancreatic Insufficiency

    PubMed Central

    Loftus, Stacie K; Cannons, Jennifer L; Incao, Arturo; Pak, Evgenia; Chen, Amy; Zerfas, Patricia M; Bryant, Mark A; Biesecker, Leslie G; Schwartzberg, Pamela L; Pavan, William J

    2005-01-01

    Pancreatic insufficiency (PI) when left untreated results in a state of malnutrition due to an inability to absorb nutrients. Frequently, PI is diagnosed as part of a larger clinical presentation in cystic fibrosis or Shwachman–Diamond syndrome. In this study, a mouse model for isolated exocrine PI was identified in a mouse line generated by a transgene insertion. The trait is inherited in an autosomal recessive pattern, and homozygous animals are growth retarded, have abnormal immunity, and have reduced life span. Mice with the disease locus, named pequeño (pq), exhibit progressive apoptosis of pancreatic acinar cells with severe exocrine acinar cell loss by 8 wk of age, while the islets and ductal tissue persist. The mutation in pq/pq mice results from a random transgene insertion. Molecular characterization of the transgene insertion site by fluorescent in situ hybridization and genomic deletion mapping identified an approximately 210-kb deletion on Chromosome 3, deleting two genes. One of these genes, Serpini2, encodes a protein that is a member of the serpin family of protease inhibitors. Reintroduction of only the Serpini2 gene by bacterial artificial chromosome transgenic complementation corrected the acinar cell defect as well as body weight and immune phenotypes, showing that deletion of Serpini2 causes the pequeño phenotype. Dietary supplementation of pancreatic enzymes also corrected body size, body weight, and immunodeficiency, and increased the life span of Serpini2-deficient mice, despite continued acinar cell loss. To our knowledge, this study describes the first characterized genetic animal model for isolated PI. Genetic complementation of the transgene insertion mutant demonstrates that Serpini2 deficiency directly results in the acinar cell apoptosis, malabsorption, and malnutrition observed in pq/pq mice. The rescue of growth retardation, immunodeficiency, and mortality by either Serpini2 bacterial artificial chromosome transgenic expression

  2. Adenoid cystic carcinoma of the parotid gland associated with salivary calculi: An unusual presentation.

    PubMed

    Shenoy, Vijendra S; Kamath, M Panduranga; Sreedharan, Suja; Suhas, S S

    2015-01-01

    Adenoid cystic carcinomas (ACC) of the head and neck are relatively rare tumors, consisting of approximately 10-15% of all salivary gland neoplasms. ACC, a slow-growing aggressive malignant tumor of salivary gland commonly seen in the submandibular, sublingual, minor salivary glands is seldom found in the parotid. Calculus, the common cause of salivary gland dysfunction is usually identified in submandibular salivary gland because of its duct anatomy and physiochemical characteristic serous secretion. We report an unusual case of co-existent presentation of ACC with salivary calculi in the parotid gland which is never been reported in the literature. Co-existence of ductal calculi and ACC is rare. Presence of parotid calculus could be due to long standing ductal obstruction by the slow-growing ACC of the parotid or other possibility is that the malignancy could have developed because of chronic irritation by parotid calculi. Confirmatory studies are required to understand its mutual pathological association.

  3. The MET Receptor Tyrosine Kinase Confers Repair of Murine Pancreatic Acinar Cells following Acute and Chronic Injury

    PubMed Central

    Gaziova, Ivana; Jackson, Daniel; Boor, Paul J.; Carter, Dwayne; Cruz-Monserrate, Zobeida; Elferink, Cornelis J.; Joshi, Aditya D.; Kaphalia, Bhupendra; Logsdon, Craig D.; Pereira de Castro, Karen; Soong, Lynn; Tao, Xinrong; Qiu, Suimin; Elferink, Lisa A.

    2016-01-01

    Acinar cells represent the primary target in necroinflammatory diseases of the pancreas, including pancreatitis. The signaling pathways guiding acinar cell repair and regeneration following injury remain poorly understood. The purpose of this study was to determine the importance of Hepatocyte Growth Factor Receptor/MET signaling as an intrinsic repair mechanism for acinar cells following acute damage and chronic alcohol-associated injury. Here, we generated mice with targeted deletion of MET in adult acinar cells (MET-/-). Acute and repetitive pancreatic injury was induced in MET-/- and control mice with cerulein, and chronic injury by feeding mice Lieber-DeCarli diets containing alcohol with or without enhancement of repetitive pancreatic injury. We examined the exocrine pancreas of these mice histologically for acinar death, edema, inflammation and collagen deposition and changes in the transcriptional program. We show that MET expression is relatively low in normal adult pancreas. However, MET levels were elevated in ductal and acinar cells in human pancreatitis specimens, consistent with a role for MET in an adaptive repair mechanism. We report that genetic deletion of MET in adult murine acinar cells was linked to increased acinar cell death, chronic inflammation and delayed recovery (regeneration) of pancreatic exocrine tissue. Notably, increased pancreatic collagen deposition was detected in MET knockout mice following repetitive injury as well alcohol-associated injury. Finally, we identified specific alterations of the pancreatic transcriptome associated with MET signaling during injury, involved in tissue repair, inflammation and endoplasmic reticulum stress. Together, these data demonstrate the importance of MET signaling for acinar repair and regeneration, a novel finding that could attenuate the symptomology of pancreatic injury. PMID:27798657

  4. Histological reclassification of parotid gland carcinomas: importance for clinicians.

    PubMed

    Stodulski, Dominik; Majewska, Hanna; Skálová, Alena; Mikaszewski, Bogusław; Biernat, Wojciech; Stankiewicz, Czesław

    2016-11-01

    Reassessment of histological specimens of salivary gland carcinomas is associated with a change of primary diagnosis in a significant number of patients. The authors evaluated the relation between reclassification/verification of histological diagnosis and the clinical course of parotid gland carcinomas. Histological and immunohistochemical examinations of 111 specimens of parotid gland carcinomas operated on during the years 1992-2010 were revised and in some cases supplemented with cytogenetic tests (FISH), to verify the diagnosis and potentially reclassify the tumours. Analysis of the clinical documentation and follow-up data of patients whose diagnosis was changed was then carried out. The prognostic factors taken into account in the evaluation of the clinical course included the T and N stage, the tumour grade and the extent of resection. The primary diagnosis was changed on review in 28 patients (25.2 %). In 16 patients, the change involved a different histological type of cancer. In six cases, what was thought to be a primary salivary gland cancer was reclassified as a secondary tumour. In four other cases, the change was made from a malignant to a benign tumour and in one case to a non-neoplastic lesion (necrotizing sialometaplasia). Additionally, in two patients with carcinoma ex pleomorphic adenoma, the malignant component was found to be of in situ type. A potentially atypical clinical course was observed in 4 out of 28 patients whose diagnosis was changed. In the case of 2 patients, the course of disease was more aggressive (dissemination, death) than predicted and less aggressive in rest of the patients. Histological reclassification/verification of parotid gland carcinomas can explain the cause of an atypical clinical course in some patients and sometimes enables doctors to implement a change in therapy.

  5. Intraoperative Radiotherapy for Parotid Cancer: A Single-Institution Experience

    SciTech Connect

    Zeidan, Youssef H.; Shiue, Kevin; Weed, Daniel; Johnstone, Peter A.; Terry, Colin; Freeman, Stephen; Krowiak, Edward; Borrowdale, Robert; Huntley, Tod; Yeh, Alex

    2012-04-01

    Purpose: Our practice policy has been to provide intraoperative radiotherapy (IORT) at resection to patients with head-and-neck malignancies considered to be at high risk of recurrence. The purpose of the present study was to review our experience with the use of IORT for primary or recurrent cancer of the parotid gland. Methods and Materials: Between 1982 and 2007, 96 patients were treated with gross total resection and IORT for primary or recurrent cancer of the parotid gland. The median age was 62.9 years (range, 14.3-88.1). Of the 96 patients, 33 had previously undergone external beam radiotherapy as a component of definitive therapy. Also, 34 patients had positive margins after surgery, and 40 had perineural invasion. IORT was administered as a single fraction of 15 or 20 Gy with 4-6-MeV electrons. The median follow-up period was 5.6 years. Results: Only 1 patient experienced local recurrence, 19 developed regional recurrence, and 12 distant recurrence. The recurrence-free survival rate at 1, 3, and 5 years was 82.0%, 68.5%, and 65.2%, respectively. The 1-, 3-, and 5-year overall survival rate after surgery and IORT was 88.4%, 66.1%, and 56.2%, respectively. No perioperative fatalities occurred. Complications developed in 26 patients and included vascular complications in 7, trismus in 6, fistulas in 4, radiation osteonecrosis in 4, flap necrosis in 2, wound dehiscence in 2, and neuropathy in 1. Of these 26 patients, 12 had recurrent disease, and 8 had undergone external beam radiotherapy before IORT. Conclusions: IORT results in effective local disease control at acceptable levels of toxicity and should be considered for patients with primary or recurrent cancer of the parotid gland.

  6. Substrate specificity of fucosyltransferase purified from human parotid saliva.

    PubMed

    Tamagawa, H; Iwakura, K; Amano, A; Shizukuishi, S; Tsunemitsu, A

    1987-03-01

    The purified fucosyltransferase from human parotid saliva was shown to transfer fucose from GDP-fucose onto the oligosaccharide chains containing the Gal beta 1----3GlcNAc or Gal beta 1----4GlcNAc/Glc sequences. Competition studies between asialotransferrin and either lacto-N-fucopentaose 1 or 2'-fucosyllactose provided evidence that both the substrates competed for a common enzyme active site. These results suggest that the fucosyltransferase activities for the three acceptors may be catalyzed by the same enzyme.

  7. Identification of miRNAs Involved in Reprogramming Acinar Cells into Insulin Producing Cells.

    PubMed

    Teichenne, Joan; Morró, Meritxell; Casellas, Alba; Jimenez, Veronica; Tellez, Noelia; Leger, Adrien; Bosch, Fatima; Ayuso, Eduard

    2015-01-01

    Reprogramming acinar cells into insulin producing cells using adenoviral (Ad)-mediated delivery of Pdx1, Ngn3 and MafA (PNM) is an innovative approach for the treatment of diabetes. Here, we aimed to investigate the molecular mechanisms involved in this process and in particular, the role of microRNAs. To this end, we performed a comparative study of acinar-to-β cell reprogramming efficiency in the rat acinar cell line AR42J and its subclone B13 after transduction with Ad-PNM. B13 cells were more efficiently reprogrammed than AR42J cells, which was demonstrated by a strong activation of β cell markers (Ins1, Ins2, IAPP, NeuroD1 and Pax4). miRNome panels were used to analyze differentially expressed miRNAs in acinar cells under four experimental conditions (i) non-transduced AR42J cells, (ii) non-transduced B13 cells, (iii) B13 cells transduced with Ad-GFP vectors and (iv) B13 cells transduced with Ad-PNM vectors. A total of 59 miRNAs were found to be differentially expressed between non-transduced AR42J and B13 cells. Specifically, the miR-200 family was completely repressed in B13 cells, suggesting that these cells exist in a less differentiated state than AR42J cells and as a consequence they present a greater plasticity. Adenoviral transduction per se induced dedifferentiation of acinar cells and 11 miRNAs were putatively involved in this process, whereas 8 miRNAs were found to be associated with PNM expression. Of note, Ad-PNM reprogrammed B13 cells presented the same levels of miR-137-3p, miR-135a-5p, miR-204-5p and miR-210-3p of those detected in islets, highlighting their role in the process. In conclusion, this study led to the identification of miRNAs that might be of compelling importance to improve acinar-to-β cell conversion for the future treatment of diabetes.

  8. Identification of miRNAs Involved in Reprogramming Acinar Cells into Insulin Producing Cells

    PubMed Central

    Teichenne, Joan; Morró, Meritxell; Casellas, Alba; Jimenez, Veronica; Tellez, Noelia; Leger, Adrien; Bosch, Fatima; Ayuso, Eduard

    2015-01-01

    Reprogramming acinar cells into insulin producing cells using adenoviral (Ad)-mediated delivery of Pdx1, Ngn3 and MafA (PNM) is an innovative approach for the treatment of diabetes. Here, we aimed to investigate the molecular mechanisms involved in this process and in particular, the role of microRNAs. To this end, we performed a comparative study of acinar-to-β cell reprogramming efficiency in the rat acinar cell line AR42J and its subclone B13 after transduction with Ad-PNM. B13 cells were more efficiently reprogrammed than AR42J cells, which was demonstrated by a strong activation of β cell markers (Ins1, Ins2, IAPP, NeuroD1 and Pax4). miRNome panels were used to analyze differentially expressed miRNAs in acinar cells under four experimental conditions (i) non-transduced AR42J cells, (ii) non-transduced B13 cells, (iii) B13 cells transduced with Ad-GFP vectors and (iv) B13 cells transduced with Ad-PNM vectors. A total of 59 miRNAs were found to be differentially expressed between non-transduced AR42J and B13 cells. Specifically, the miR-200 family was completely repressed in B13 cells, suggesting that these cells exist in a less differentiated state than AR42J cells and as a consequence they present a greater plasticity. Adenoviral transduction per se induced dedifferentiation of acinar cells and 11 miRNAs were putatively involved in this process, whereas 8 miRNAs were found to be associated with PNM expression. Of note, Ad-PNM reprogrammed B13 cells presented the same levels of miR-137-3p, miR-135a-5p, miR-204-5p and miR-210-3p of those detected in islets, highlighting their role in the process. In conclusion, this study led to the identification of miRNAs that might be of compelling importance to improve acinar-to-β cell conversion for the future treatment of diabetes. PMID:26690959

  9. New models of experimental parotitis and parotid gland distension in rats.

    PubMed

    Okada-Ogawa, Akiko; Shinoda, Masamichi; Honda, Kuniya; Iwata, Koichi

    2012-01-01

    A significant reduction of the escape threshold to mechanical stimulation of the lateral facial skin was observed bilaterally at days 2 and 3 after unilateral complete Freund's adjuvant (CFA) administration into parotid gland. A slight reduction of mechanical escape threshold was also observed in rats with saline administration. The parotid gland inflammation was verified and quantified by measuring the tissue Evans' blue dye extravasation. The Evans' blue concentration in the parotid gland tissues was significantly greater in the CFA-injected rats than that of the saline-injected rats at 72 h after treatment. On day 10 after CFA administration into the parotid gland, the Evans' blue concentration was recovered to the control level. The administration of capsaicin into the parotid gland did not alter neuronal activities in the transition zone between the trigeminal spinal subnucleus interpolaris and caudalis (Vi/Vc). In contrast, capsaicin administration induced significant increases in the receptive field size and mechanical and cold responses of neurons located in superficial laminae of the C1/C2. The subgroup of C1/C2 neurons responded to mechanical distension of the parotid gland, whereas no Vi/Vc neurons responded to parotid distension.

  10. Effects of shock waves on oxidative stress in parotid gland of rat.

    PubMed

    Garca, M Fatih; Kavak, Servet; Gecit, Ilhan; Meral, Ismail; Demir, Halit; Turan, Mahfuz; Çeğin, Bilal; Bektas, Hava; Çankaya, Hakan

    2014-06-01

    This study was designed to investigate whether extracorporeal shock wave lithotripsy (ESWL) exposure to parotid gland produces an oxidative stress in parotid glands of rats. Twelve male Wistar-albino rats, 6 months of age with an average body weight of 250-300 g, were divided randomly into two groups, each consisting of six rats. The animals in the first group did not receive any treatment and served as control. The left parotid glands of animals in group 2 (ESWL treated) received a thousand 18 kV shock waves after anesthetizing the rats with 50 mg/kg of ketamine. The animals in both groups were killed 72 hours after the ESWL treatment, and the parotid glands were harvested for the determination of lipid peroxidation product malondialdehyde (MDA), antioxidant glutathione (GSH) levels and the activities of antioxidant enzymes such as superoxide dismutase (SOD), GSH-Px and catalase (CAT). It was found that MDA level increased in parotid glands of rats after the ESWL treatment. The SOD, GSH-Px and CAT enzyme activities, and the level of antioxidant GSH decreased in parotid gland of rats after the ESWL treatment. It was concluded that short-term ESWL treatment caused an increase in the free radical production and a decrease in the antioxidant enzyme activity in parotid glands of ESWL-treated rats.

  11. Effects of dopamine on adenylyl cyclase activity and amylase secretion in rat parotid tissue.

    PubMed

    Hatta, S; Amemiya, N; Takemura, H; Ohshika, H

    1995-06-01

    Several previous studies have shown that dopamine causes amylase secretion from rat parotid tissue. However, the mechanism of this dopamine action is still unclear. The present study was designed to characterize dopamine action in rat parotid gland tissue by examining the effects of dopamine on cyclic AMP accumulation, adenylyl cyclase activity, and amylase release. Dopamine significantly enhanced accumulation of cyclic AMP in parotid slices and stimulated adenylyl cyclase activity in parotid membrane preparations. It also significantly stimulated amylase release from parotid slices. The stimulatory effects of dopamine on cyclic AMP accumulation, adenylyl cyclase activity, and amylase release were effectively blocked with propranolol, a beta-adrenergic antagonist, but not by either SCH 23390, a preferential D1 antagonist, or butaclamol, a preferential D2 antagonist. No substantial specific binding sites for D1 receptors were detectable by [3H]SCH 23390 binding in parotid membranes. These results suggest that the stimulatory effect of dopamine on amylase secretion in rat parotid tissue is not mediated through specific D1 dopamine receptors but rather through beta-adrenergic receptors.

  12. Variant rabbit hemorrhagic disease virus in young rabbits, Spain.

    PubMed

    Dalton, Kevin P; Nicieza, Inés; Balseiro, Ana; Muguerza, María A; Rosell, Joan M; Casais, Rosa; Álvarez, Ángel L; Parra, Francisco

    2012-12-01

    Outbreaks of rabbit hemorrhagic disease have occurred recently in young rabbits on farms on the Iberian Peninsula where rabbits were previously vaccinated. Investigation identified a rabbit hemorrhagic disease virus variant genetically related to apathogenic rabbit caliciviruses. Improved antivirus strategies are needed to slow the spread of this pathogen.

  13. Sudden disappearance of the blood flow in a case of pancreatic acinar cell carcinoma.

    PubMed

    Kanno, Atsushi; Masamune, Atsushi; Hamada, Shin; Kikuta, Kazuhiro; Kume, Kiyoshi; Hirota, Morihisa; Shima, Kentaro; Okada, Takaho; Motoi, Fuyuhiko; Fujishima, Fumiyoshi; Ishida, Kazuyuki; Unno, Michiaki; Shimosegawa, Tooru

    2014-01-01

    A 55-year-old man was referred to our hospital for a further examination of a pancreatic cystic tumor with a solid component exhibiting vascularity. A few days later, the patient was admitted with a complaint of sudden severe epigastric pain. Enhanced CT showed the loss of vascularity in the tumor. In particular, contrast-enhanced endoscopic ultrasonography (EUS) clearly demonstrated the disappearance of the blood flow, and a histological examination revealed acinar cell carcinoma with central necrosis. To our knowledge, this is the first case in the literature of acinar cell carcinoma associated with the sudden disappearance of vascularity. In this case, contrast-enhanced harmonic EUS was especially useful for assessing the degree of vascularity.

  14. Dysgenetic polycystic disease of the parotid gland: Report of a case and review of the literature

    PubMed Central

    Kumar, KR Ashok; Mahadesh, Jyothi; Setty, Suhas

    2013-01-01

    Dysgenetic polycystic disease (DPD) is a rare cystic lesion affecting mainly the parotid salivary glands with only 14 reported cases in English literature. DPD of parotids is more common in females, common in younger age group, mostly bilateral in occurrence and commonly affects the superficial lobe. Surgery is performed for symptomatic relief and cosmosis. We report a case of a unilateral DPD of the parotid gland with distinctive histopathology. Patient was treated by performing total parotidectomy with preservation of the facial nerve. PMID:24250087

  15. Benign lymphoepithelial cysts of parotid and submandibular glands in a HIV-positive patient

    PubMed Central

    Shivhare, Peeyush; Shankarnarayan, Lata; Jambunath, Usha; Basavaraju, Sowbhagya Malligere

    2015-01-01

    Patients with human immunodeficiency virus (HIV) infection have been reported to have parotid swellings of various types such as diffuse infiltrative lymphocytosis syndrome, parotitis, intraparotid lymphadenopathy, benign lymphoepithelial cyst (BLEC), as well as salivary gland neoplasms such as adenoid cystic carcinoma, Kaposi sarcoma and lymphoma. LECs in the parotid gland are uncommon benign entities with increased incidence associated with HIV infection. We are presenting a case of 28-year-old HIV-positive patient with BLECs in the parotid and submandibular glands. PMID:26097320

  16. Intracellular mediators of Na -K pump activity in guinea pig pancreatic acinar cells

    SciTech Connect

    Hootman, S.R.; Ochs, D.L.; Williams, J.A.

    1985-10-01

    The involvement of CaS and cyclic nucleotides in neurohormonal regulation of Na -K -ATPase (Na -K pump) activity in guinea pig pancreatic acinar cells was investigated. Changes in Na+-K+ pump activity elicited by secretagogues were assessed by (3H)ouabain binding and by ouabain-sensitive YWRb uptake. Carbachol (CCh) and cholecystokinin octapeptide (CCK-8) each stimulated both ouabain-sensitive 86Rb+ uptake and equilibrium binding of (TH)ouabain by approximately 60%. Secretin increased both indicators of Na+-K+ pump activity by approximately 40% as did forskolin, 8-bromo- and dibutyryl cAMP, theophylline, and isobutylmethylxanthine. Incubation of acinar cells in CaS -free HEPES-buffered Ringer (HR) with 0.5 mM EGTA reduced the stimulatory effects of CCh and CCK-8 by up to 90% but caused only a small reduction in the effects of secretin, forskolin, and cAMP analogues. In addition, CCh, CCK-8, secretin, and forskolin each stimulated ouabain-insensitive 86Rb+ uptake by acinar cells. The increase elicited by CCh and CCK-8 was greatly reduced in the absence of extracellular CaS , while that caused by the latter two agents was not substantially altered. The effects of secretagogues on free CaS levels in pancreatic acinar cells also were investigated with quin-2, a fluorescent CaS chelator. Basal intracellular CaS concentration ((CaS )i) was 161 nM in resting cells and increased to 713 and 803 nM within 15 s after addition of 100 microM CCh or 10 nM CCK-8, respectively.

  17. Loss of Ifnar1 in Pancreatic Acinar Cells Ameliorates the Disease Course of Acute Pancreatitis

    PubMed Central

    Miller, Katharina J.; Raulefs, Susanne; Kong, Bo; Steiger, Katja; Regel, Ivonne; Gewies, Andreas; Kleeff, Jörg; Michalski, Christoph W.

    2015-01-01

    Type I interferon constitutes an essential component of the combinational therapy against viral disease. Acute pancreatitis is one side effect of type I interferon-based therapy, implying that activation of type I interferon signaling affects the homeostasis and integrity of pancreatic acinar cells. Here, we investigated the role of type I interferon signaling in pancreatic acinar cells using a caerulein-induced murine model of acute pancreatitis. Pancreas-specific ablation of interferon (alpha and beta) receptor 1 (Ifnar1) partially protected animals from caerulein-induced pancreatitis, as demonstrated by reduced tissue damage. Profiling of infiltrating immune cells revealed that this dampened tissue damage response correlated with the number of macrophages in the pancreas. Pharmacologic depletion of macrophages reversed the protective effect of Ifnar1 deficiency. Furthermore, expression of chemokine (C-C motif) ligand 2 (Ccl2), a potent factor for macrophage recruitment, was significantly increased in the Ifnar1-deficient pancreas. Thus, type I interferon signaling in pancreatic acinar cells controls pancreatic homeostasis by affecting the macrophage-mediated inflammatory response in the pancreas. PMID:26618925

  18. Coupling of guanine nucleotide inhibitory protein to somatostatin receptors on pancreatic acinar membranes

    SciTech Connect

    Sakamoto, C.; Matozaki, T.; Nagao, M.; Baba, S.

    1987-09-01

    Guanine nucleotides and pertussis toxin were used to investigate whether somatostatin receptors interact with the guanine nucleotide inhibitory protein (NI) on pancreatic acinar membranes in the rat. Guanine nucleotides reduced /sup 125/I-(Tyr/sup 1/)somatostatin binding to acinar membranes up to 80%, with rank order of potency being 5'-guanylyl imidodiphosphate (Gpp(NH)p)>GTP>TDP>GMP. Scatchard analysis revealed that the decrease in somatostatin binding caused by Gpp(NH)p was due to the decrease in the maximum binding capacity without a significant change in the binding affinity. The inhibitory effect of Gpp(NH)p was partially abolished in the absence of Mg/sup 2 +/. When pancreatic acini were treated with 1 ..mu..g/ml pertussis toxin for 4 h, subsequent /sup 125/I-(Tyr/sup 1/)somatostatin binding to acinar membranes was reduced. Pertussis toxin treatment also abolished the inhibitory effect of somatostatin on vasoactive intestinal peptide-stimulated increase in cellular content of adenosine 3',5'-cyclic monophosphate (cAMP) in the acini. The present results suggest that 1) somatostatin probably functions in the pancreas to regulate adenylate cyclase enzyme system via Ni, 2) the extent of modification of Ni is correlated with the ability of somatostatin to inhibit cAMP accumulation in acini, and 3) guanine nucleotides also inhibit somatostatin binding to its receptor.

  19. Altered Gene Expression in Cerulein-Stimulated Pancreatic Acinar Cells: Pathologic Mechanism of Acute Pancreatitis

    PubMed Central

    Yu, Ji Hoon; Lim, Joo Weon

    2009-01-01

    Acute pancreatitis is a multifactorial disease associated with the premature activation of digestive enzymes. The genes expressed in pancreatic acinar cells determine the severity of the disease. The present study determined the differentially expressed genes in pancreatic acinar cells treated with cerulein as an in vitro model of acute pancreatitis. Pancreatic acinar AR42J cells were stimulated with 10-8 M cerulein for 4 h, and genes with altered expression were identified using a cDNA microarray for 4,000 rat genes and validated by real-time PCR. These genes showed a 2.5-fold or higher increase with cerulein: lithostatin, guanylate cyclase, myosin light chain kinase 2, cathepsin C, progestin-induced protein, and pancreatic trypsin 2. Stathin 1 and ribosomal protein S13 showed a 2.5-fold or higher decreases in expression. Real-time PCR analysis showed time-dependent alterations of these genes. Using commercially available antibodies specific for guanylate cyclase, myosin light chain kinase 2, and cathepsin C, a time-dependent increase in these proteins were observed by Western blotting. Thus, disturbances in proliferation, differentiation, cytoskeleton arrangement, enzyme activity, and secretion may be underlying mechanisms of acute pancreatitis. PMID:20054485

  20. Early acinar cell changes in caerulein-induced interstitial acute pancreatitis in the rat.

    PubMed

    Grönroos, J M; Aho, H J; Hietaranta, A J; Nevalainen, T J

    1991-01-01

    Early ultrastructural and immunohistochemical changes caused by supramaximal secretory stimulation with caerulein were studied in the rat pancreas. The morphological basis for the earlier reported decrease of pancreatic juice secretion after supramaximal caerulein was the appearance of swollen and irregular zymogen-like material containing structures with short segments of budding bristle-coated membranes in the apical parts of acinar cells. Images of exocytosis of zymogen granules were only few. Later, marked vacuolization and signs of autophagocytosis are seen in the basal cytoplasm. Immunohistochemistry showed that the large zymogen containing structures were intensively labelled for trypsin at the early stages of the experiment (4-30 min). Later (1-2 h), the vacuoles were empty or contained occasional, small-labelled granules only. The pancreozymin-receptor antagonist proglumide as well as cycloleucine that inhibits protein synthesis by inhibiting the synthesis of S-adenosylmethionine, effectively prevented the caerulein induced acinar cell changes. The irregular zymogen containing structures with coated pits on their surface indicate disturbed zymogen granule formation leading to the accumulation of large lakes of zymogen material and finally to marked autophagocytosis in acinar cells. The effects of caerulein are receptor-mediated and depend on the process of methylation in the formation of zymogen granules.

  1. Bath and Shower Effects in the Rat Parotid Gland Explain Increased Relative Risk of Parotid Gland Dysfunction After Intensity-Modulated Radiotherapy

    SciTech Connect

    Luijk, Peter van Faber, Hette; Schippers, Jacobus M.; Brandenburg, Sytze; Langendijk, Johannes A.; Meertens, Harm; Coppes, Robert P.

    2009-07-15

    Purpose: To assess in a rat model whether adding a subtolerance dose in a region adjacent to a high-dose irradiated subvolume of the parotid gland influences its response (bath-and-shower effect). Methods and Materials: Irradiation of the whole, cranial 50%, and/or the caudal 50% of the parotid glands of Wistar rats was performed using 150-MeV protons. To determine suitable (i.e., subtolerance) dose levels for a bath-dose, both whole parotid glands were irradiated with 5 to 25 Gy. Subsequently groups of Wistar rats received 30 Gy to the caudal 50% (shower) and 0 to 10 Gy to the cranial 50% (bath) of both parotid glands. Stimulated saliva flow rate (function) was measured before and up to 240 days after irradiation. Results: Irradiation of both glands up to a dose of 10 Gy did not result in late loss of function and is thus regarded subtolerance. Addition of a dose bath of 1 to 10 Gy to a high-dose in the caudal 50% of the glands resulted in enhanced function loss. Conclusion: Similar to the spinal cord, the parotid gland demonstrates a bath and shower effect, which may explain the less-than-expected sparing of function after IMRT.

  2. [Acute neonatal suppurative parotiditis: about three clinical cases and review of the literature].

    PubMed

    Isfaoun, Zineb; Radouani, Mohammed Amine; Azzaoui, Sihame; Knouni, Houria; Aguenaou, Hassan; Barkat, Amina

    2016-01-01

    The following case study reports three cases of neonatal bacterial parotiditis observed over a period of seven months. Diagnosis is often based on patient's clinical features: they typically include hyperthermia, swelling, erythema, warmth as well as local tenderness and purulent discharge at Stensen duct during the massage of the parotid. The clinical diagnosis is confirmed by ultrasound and by culture of parotid purulent secretion. They are mainly of nosocomial origin and are generally caused by prematurity and dehydration. Early treatment improves patient outcome. Risk factors such as age should lead clinicians to start empiric antibiotic therapy first and then antibiotic therapy based on direct examination of pus extracted from Stensen duct. Staphylococcus aureus, Streptococcus Viridans and anaerobic germs are most commonly isolated. Acute parotiditis are extremely rare in the neonatal period: less than 50 cases have been reported in the literature. We here report three rather peculiar cases. The diagnosis was suspected on the basis of signs of local inflammation.

  3. Surgical management of parotid salivary duct rupture secondary to non-iatrogenic trauma in a dog

    PubMed Central

    YOON, Hun-Young; MIN, Byong-Su; KIM, Sun-Young; LEE, Da-Eun; KIM, Jung-Hyun

    2016-01-01

    A 3-year-old French bulldog presented for evaluation of recurrent swelling and a fistula on the right cheek after a dog fight. A large volume of serous fluids was identified on the wound immediately after atropine drops. A diagnosis of parotid salivary duct rupture secondary to trauma was made. On surgical exploration, the thickened proximal segment of the severed duct was identified and circumferentially double ligated with 3–0 silk. No evidence of swelling and normal appearance of the parotid salivary gland were identified 4 months postoperative recheck. No further problems were noted 10 months postoperatively phone-call. To the author’s knowledge, this is the first reported case of successful proximal parotid duct ligation of parotid salivary duct rupture secondary to non-iatrogenic trauma. PMID:27666341

  4. Hydatid cyst of parotid: Report of unusual cytological findings extending the cytomorphological spectrum.

    PubMed

    Arora, Vinod Kumar; Chopra, Neha; Singh, Poorva; Venugopal, Vasantha Kumar; Narang, Salil

    2016-09-01

    Hydatid disease is a zoonotic infestation caused by larval cestode of genus Echinococcus. Cystic form of this infection mostly involves liver and lung. Hydatid disease of the parotid gland is very rare even in endemic areas and is often clinically mistaken for parotid tumors or cysts. The presence of protoscolices, laminated membranes, and isolated hooklets are characteristic cytological features observed on fine-needle aspirate from hydatid cysts. We report unusual cytological features from a hydatid cyst of parotid in a 13-year-old girl. She presented with a slowly enlarging hard mass in left parotid. Fine-needle aspiration yielded slightly turbid fluid. Smears from the sediment revealed naked parasitic micronuclei, fragments of germinative layer (endocyst), and abortive brood capsules (buds from endocyst) seen as spherical structures with multiple parasitic nuclei. Some of these spherical structures were degenerated with recognizable nuclei and others were completely necrotic. Diagn. Cytopathol. 2016;44:770-773. © 2016 Wiley Periodicals, Inc.

  5. Myoparasitism mimicking parotid swelling: a rare presentation of cysticercosis

    PubMed Central

    Tewari, Sandeep; Singh, Saumya; Jaiswal, Vaibhav; Mishra, Anand Kumar

    2014-01-01

    Muscular infestation with larval stage of Taenia solium is a well-recognised entity but cysticercosis of the head and neck region is a rarity. We present a case of 35-year-old young man with diffuse swelling of 3.5×4 cm in the parotid region on the right side of the face with signs of inflammation. Diagnosis was established on high-resolution ultrasonography which revealed it to be of parasitic origin. The patient was managed with antihelminthic pharmacotherapy and improved within a month. Thus cysticercosis should be considered in the differential diagnosis of subcutaneous swellings of the head and neck region, especially in endemic zones and it must be investigated well with appropriate imaging modalities so that inadvertent surgery can be avoided. PMID:24842360

  6. [Radiation therapy for pleomorphic adenoma of the parotid].

    PubMed

    Jardel, P; Fakhry, N; Makeieff, M; Ferrie, J-C; Milin, S; Righini, C; Lacout, A; Costes, V; Malard, O; Marcy, P-Y; Guevara, N; Odin, G; Bensadoun, R-J; Thariat, J

    2014-01-01

    Parotid pleomorphic adenoma is the most frequent tumor of salivary glands. The prognosis depends on the recurrences because they could lead to iatrogenic events (facial paralysis). Moreover the risk of malignant transformation increases with the number of local relapses. This article aims at reviewing histological and radiological criteria and the surgical techniques. To improve local control, adjuvant irradiation (in first intention or after recurrence) may be useful but is still controversial for benign tumors in young patients with a risk of radio-induced cancer. We listed studies in which adjuvant radiotherapy was used so as to define its place in the treatment strategy. Prognostic factors were found by some authors. Other studies have to be done before strong evidence-based recommendations are issued.

  7. Massive transcranial parotid pleomorphic adenoma: recurrence after 30 years.

    PubMed

    Strub, Graham M; Georgolios, Alexandros; Graham, Robert S; Powers, Celeste N; Coelho, Daniel H

    2012-10-01

    Pleomorphic adenoma, also known as benign mixed tumor, is the most common tumor affecting the parotid gland and can reach massive size; however, intracranial invasion is rare. Recurrence of pleomorphic adenoma after excision is a well-known phenomenon and can present decades after resection of the primary tumor. Here we present the case of a 53-year-old man who presented to our clinic with ear fullness, otalgia, and hearing loss 30 years after undergoing total parotidectomy and external beam radiotherapy for pleomorphic adenoma. Magnetic resonance imaging revealed a massive transcranial tumor invading the mastoid cavity, the dura of the posterior fossa, the fallopian and semicircular canals, the jugular foramen, the lateral infratemporal fossa skull base, the sigmoid and transverse sinuses, and the superior parapharyngeal region. Gross examination and histopathological studies confirmed that the mass was a recurrent pleomorphic adenoma. Here we discuss the features of recurrent pleomorphic adenoma and review the current literature.

  8. INFECTIOUS PAPILLOMATOSIS OF RABBITS

    PubMed Central

    Shope, Richard E.; Hurst, E. Weston

    1933-01-01

    A papilloma has been observed in wild cottontail rabbits and has been found to be transmissible to both wild and domestic rabbits. The clinical and pathological pictures of the condition have been described. It has been found that the causative agent is readily filtrable through Berkefeld but not regularly through Seitz filters, that it stores well in glycerol, that it is still active after heating to 67°C. for 30 minutes, but not after heating to 70°C., and that it exhibits a marked tropism for cutaneous epithelium. The activities and properties of the papilloma-producing agent warrant its classification as a filtrable virus. Rabbits carrying experimentally produced papillomata are partially or completely immune to reinfection and, furthermore, their sera partially or completely neutralize the causative virus. The disease is transmissible in series through wild rabbits and virus of wild rabbit origin is readily transmissible to domestic rabbits, producing in this species papillomata identical in appearance with those found in wild rabbits. However, the condition is not transmissible in series through domestic rabbits. The possible significance of this observation has been discussed. The virus of infectious papillomatosis is not related immunologically to either the virus of infectious fibroma or to that of infectious myxoma of rabbits. PMID:19870219

  9. Neurologic Evaluation of Acute Lacrimomimetic Effect of Cyclosporine in an Experimental Rabbit Dry Eye Model

    PubMed Central

    Toshida, Hiroshi; Nguyen, Doan H.; Beuerman, Roger W.; Murakami, Akira

    2010-01-01

    PURPOSE To evaluate neurologically acute lacrimation caused by cyclosporine (CsA) eyedrops in rabbit. METHODS Normal adult male New Zealand White rabbits and those that underwent parasympathectomy each received a single instillation of 0.1% CsA or vehicle eyedrops. Schirmer tear test (STT) results, flow rate of lacrimal gland (LG) fluid from the excretory lacrimal duct of the main LG, and blink rate (over a 3-minute period) were measured before and after instillation of CsA or vehicle. Light microscopy was performed to examine the main LG in vitro. Protein release from LG fragments was assessed after incubation with CsA for 30 minutes. RESULTS In normal rabbits, the STT value and the flow rate of LG fluid were significantly increased after treatment with CsA compared with vehicle (P < 0.05). In contrast, no changes were found in denervated eyes. The blink rate of CsA-treated eyes was significantly higher than that of vehicle- treated eyes in normal rabbits (P < 0.005), whereas that of denervated eyes decreased significantly after CsA instillation compared with before administration (P < 0.005). Light microscopy showed that the cytoplasm of acinar cells was packed with secretory granules in denervated LG tissue 7 days after parasympathectomy. The same finding was observed 3 hours after CsA instillation. CsA had no stimulatory effect on protein release by acinar cells in LG fragments at all concentrations tested. CONCLUSIONS These results suggest that CsA has no direct effect on tear fluid secretion from the LG in an acute model. Instead, CsA increases reflex tear flow. PMID:19218606

  10. Congenital Unilateral Agenesis of the Parotid Gland: A Case Report and Review of the Literature

    PubMed Central

    Teymoortash, Afshin

    2016-01-01

    Congenital unilateral agenesis of the parotid gland is a rare condition with only few cases reported in the literature. A review of 21 cases in the available literature is presented in this article. We report on a further case of a 34-year-old woman with agenesis of the left parotid gland and lipoma of the right cheek. Clinicopathological characteristics of described cases in the literature were discussed. PMID:27895943

  11. [Superficial angiomyxoma of the parotid region and review of the literature].

    PubMed

    Rosado Rodríguez, Pablo; de Vicente, Juan C; de Villalaín, Lucas; Blanco, Verónica

    2012-01-01

    Superficial angiomyxoma (SA) is a rare benign cutaneous neoplasm first described by Allen et al in 1988. To the best of our knowledge, we report the first case of superficial angiomyxoma located in the parotid region. We also stress the importance of distinguishing this entity from other lesions that may be involved in this location such as cutaneous neoplasms, parotid tumours or cysts. We emphasise the need to rule out the Carney complex, which has been associated with these tumours.

  12. Bioactivity of diopside ceramic in human parotid saliva.

    PubMed

    De Aza, Piedad N; Luklinska, Zofia B; Anseau, Michel

    2005-04-01

    Diopside ceramic pellets with a nominal composition of 55.5 wt % SiO(2)-25.9 wt % CaO-18.0 wt % MgO were soaked in human parotid saliva (HPS) over different time intervals, to investigate the behavior of the material in a natural medium of high protein content. The results showed the formation of a hydroxyapatite (HA)-like layer on the surface of the ceramic, and suggested that the mechanism of HA-like layer formation in saliva was similar to that showed in vitro test by other silica-based materials. The HA-like layer formed at the interface was found to be compact, continuous, and composed of many small crystallites with ultrastructure similar to that of natural cortical bone and dentine. The study concluded that the high pH conditions (9.8) existing right at the ceramic/human parotid saliva interface promoted HA-like phase precipitation. At this stage of the study, it is possible to suggest that the diopside ceramic could be of interest in specific periodontal applications for bone restorative purposes. Morphology, structure, and composition of the interfacial reaction product were examined by Scanning and Transmission Electron Microscopy techniques (SEM and TEM), combined with Energy Dispersive X-say Spectroscopy (EDS). Changes in ionic concentrations were measured using Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES), while the pH right at the interface of diopside/PHS were determined with an Ion Sensitive Field Effect Transistor (ISFET-Meter) instruments.

  13. Adaptive parotid gland hypertrophy induced by dietary treatment of GSE in rats.

    PubMed

    Inoue, Kaoru; Morikawa, Tomomi; Matsuo, Saori; Tamura, Kei; Takahashi, Miwa; Yoshida, Midori

    2014-08-01

    In a 13-week feeding toxicity study of grape skin extract (GSE) performed previously, 5.0% GSE showed diffuse hypertrophy and basophilia in rat parotid glands. To clarify whether the change in the parotid glands was an adverse effect of GSE, 6-week-old male F344 rats were fed a diet containing 5.0% GSE or were administered a dose corresponding to the dietary concentration via gavage for 4 weeks, and the treatment was stopped for 2 weeks. To ascertain the effect of astringency, other animals were fed a diet containing 5.0% tannic acid (TA) using the same protocol as the GSE feed group. Control groups were fed a basal diet or were administered sterilized distilled water by gavage. In the GSE and TA feed groups, diffuse severe hypertrophy and basophilia in the parotid glandular epithelial cells were observed. Macroscopic, microscopic, and ultrastructural characteristics consistent with cellular hypertrophy was less apparent after the recovery period in both feed groups. In contrast, no changes were observed in the parotid glands of the gavage GSE and control groups at week 4. Based on these findings of parotid hypertrophy without cytotoxicity, the data from this and previous studies suggest that hypertrophy of the parotid glands induced by feeding treatment with GSE is an adaptive non-adverse effect that is reversible upon removal of the sialotrophic agent.

  14. Parasympathetic denervation increases responses to VIP in isolated rat parotid acini

    SciTech Connect

    McMillian, M.K.; Talamo, B.R. )

    1989-07-01

    Vasoactive intestinal peptide (VIP) is a putative neurotransmitter found in the salivary glands of many species, including the rat parotid gland. Parasympathetic denervation has been reported to deplete VIP in the rat parotid gland and to lead to supersensitivity to this peptide in vivo. We have compared the effects of VIP on acini isolated from parasympathetically denervated and unoperated parotid glands to examine possible supersensitivity to the peptide in vitro. VIP normally produced responses similar to those obtained with a low concentration of the beta adrenergic agonist isoproterenol (ISO), but strikingly different from the effects obtained with the muscarinic agonist carbachol (CARB). In parotid membrane preparations, VIP stimulated adenylate cyclase activity. Dissociated acini treated with VIP showed increases in cAMP accumulation and amylase release which were potentiated by forskolin and also by inhibition of phosphodiesterase. After parasympathetic denervation, maximal effects of VIP on adenylate cyclase, cAMP accumulation and amylase release in intact cells were increased two- to five-fold over contralateral control (or unoperated) parotid responses. The increase in adenylate cyclase-mediated responses after denervation was specific to VIP; there was no increased response nor increased sensitivity of any of these responses to ISO. Specific (125I)VIP binding to parotid acini increased two-fold per gland and three-fold per mg of protein after denervation; this probably explains the observed increases in the response to VIP.

  15. The effect of hyposmotic and isosmotic cell swelling on the intracellular [Ca2+] in lactating rat mammary acinar cells.

    PubMed

    Shennan, D B; Grant, A C G; Gow, I F

    2002-04-01

    The effect of hyposmotic and isosmotic cell swelling on the free intracellular calcium concentration ([Ca2+]i) in rat mammary acinar cells has been examined using the fura-2 dye technique. Ahyposmotic shock (40% reduction) increased the [Ca2+]i in rat mammary acinar cells in a fashion which was transient; the [Ca2+]i returned to a value similar to that found under isomotic conditions within 180 sec. The increase in the [Ca2+]i was dependent upon the extent of the osmotic shock. The hyposmotically-activated increase in the [Ca2+]i could not be attributed to a reduction in extracellular Na+ or a change in the ionic strength of the incubation medium. Thapsigargin (1 microM) enhanced the hyposmotically-activated increase in the [Ca2+]i. Isosmotic swelling of rat mammary acinar cells, using urea, had no significant effect on the [Ca2+]i. Similarly, a hyperosmotic shock did not affect the [Ca2+]i in rat mammary acinar cells. It appears that the effect of cell swelling on the [Ca2+]i in rat mammary acinar cells depends on how the cells are swollen (hyposmotic vs. isosmotic). This finding may have important physiological implications given that it is predicted that mammary cell volume will change in vivo under isomotic conditions.

  16. Membrane Proteome Analysis of Cerulein-Stimulated Pancreatic Acinar Cells: Implication for Early Event of Acute Pancreatitis

    PubMed Central

    Lee, Jangwon; Seo, Ji Hye; Lim, Joo Weon

    2010-01-01

    Background/Aims Cerulein pancreatitis is similar to human edematous pancreatitis with dysregulation of the production and secretion of digestive enzymes, edema formation, cytoplasmic vacuolization and the death of acinar cells. We hypothesized that membrane proteins may be altered as the early event during the induction of acute pancreatitis. Present study aims to determine the differentially expressed proteins in the membranes of cerulein-treated pancreatic acinar cells. Methods Pancreatic acinar AR42J cells were treated with 10-8 M cerulein for 1 hour. Membrane proteins were isolated from the cells and separated by two-dimensional electrophoresis using pH gradients of 5-8. Membrane proteins were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of the peptide digests. The differentially expressed proteins, whose expression levels were more or less than three-fold in cerulein-treated cells, were analyzed. Results Two differentially expressed proteins (mannan-binding lectin-associated serine protease-2, heat shock protein 60) were up-regulated while four proteins (protein disulfide isomerase, γ-actin, isocitrate dehydrogenase 3, seven in absentia homolog 1A) were down-regulated by cerulein treatment in pancreatic acinar cells. These proteins are related to cell signaling, oxidative stress, and cytoskeleton arrangement. Conclusions Oxidative stress may induce cerulein-induced cell injury and disturbances in defense mechanism in pancreatic acinar cells. PMID:20479917

  17. Autoantibody Production in Rabbits

    PubMed Central

    Asherson, G. L.; Rose, M. Elaine

    1963-01-01

    The finding that the serum of apparently healthy rabbits fixed complement with rabbit liver and kidney has been confirmed. Experimental infection of rabbits with Eimeria stiedae, the cause of hepatic coccidiosis, led to a rise in the titre of serum complement-fixing factors. The rise was statistically significant 14, 21 and 28 days after infection. The factors were regarded as antibodies because they behaved as macroglobulins on diethylaminoethyl—cellulose chromatography and sucrose gradient centrifugation, and as autoantibodies because they fixed complement with the kidney of the rabbits in which they occurred. The antibody reacted with widely distributed antigen(s) with high activity in brain and low activity in skeletal muscle. The possibility that coccidial infection may be responsible for the natural autoantibody of rabbits is discussed. PMID:13965167

  18. Nicotine derived genotoxic effects in human primary parotid gland cells as assessed in vitro by comet assay, cytokinesis-block micronucleus test and chromosome aberrations test.

    PubMed

    Ginzkey, Christian; Steussloff, Gudrun; Koehler, Christian; Burghartz, Marc; Scherzed, Agmal; Hackenberg, Stephan; Hagen, Rudolf; Kleinsasser, Norbert H

    2014-08-01

    Genotoxic effects of nicotine were described in different human cells including salivary gland cells. Based on the high nicotine concentration in saliva of smokers or patients using therapeutic nicotine patches, the current study was performed to evaluate the genotoxic potential of nicotine in human salivary gland cells. Therefore, primary salivary gland cells from 10 patients undergoing parotid gland surgery were exposed to nicotine concentrations between 1 μM and 1000 μM for 1 h in the absence of exogenous metabolic activation. The acinar phenotype was proven by immunofluorescent staining of alpha-amylase. Genotoxic effects were evaluated using the Comet assay, the micronucleus test and the chromosome aberration test. Cytotoxicity and apoptosis were determined by trypan blue exclusion test and Caspase-3 assay. Nicotine was able to induce genotoxic effects in all three assays. The chromosome aberration test was the most sensitive and increases in numerical and structural (chromatid-type and chromosome-type) aberrations were seen at ≥1 μM, whereas increases in micronuclei frequency were detected at 10 μM and DNA damage as measured in the Comet assay was noted at >100 μM. No cytotoxic damage or influence of apoptosis could be demonstrated. Nicotine as a possible risk factor for tumor initiation in salivary glands is still discussed controversially. Our results demonstrated the potential of nicotine to induce genotoxic effects in salivary gland cells. These results were observed at saliva nicotine levels similar to those found after oral or transdermal exposure to nicotine and suggest the necessity of careful monitoring of the use of nicotine in humans.

  19. Insulin Protects Pancreatic Acinar Cells from Palmitoleic Acid-induced Cellular Injury*

    PubMed Central

    Samad, Aysha; James, Andrew; Wong, James; Mankad, Parini; Whitehouse, John; Patel, Waseema; Alves-Simoes, Marta; Siriwardena, Ajith K.; Bruce, Jason I. E.

    2014-01-01

    Acute pancreatitis is a serious and sometimes fatal inflammatory disease where the pancreas digests itself. The non-oxidative ethanol metabolites palmitoleic acid (POA) and POA-ethylester (POAEE) are reported to induce pancreatitis caused by impaired mitochondrial metabolism, cytosolic Ca2+ ([Ca2+]i) overload and necrosis of pancreatic acinar cells. Metabolism and [Ca2+]i are linked critically by the ATP-driven plasma membrane Ca2+-ATPase (PMCA) important for maintaining low resting [Ca2+]i. The aim of the current study was to test the protective effects of insulin on cellular injury induced by the pancreatitis-inducing agents, ethanol, POA, and POAEE. Rat pancreatic acinar cells were isolated by collagenase digestion and [Ca2+]i was measured by fura-2 imaging. An in situ [Ca2+]i clearance assay was used to assess PMCA activity. Magnesium green (MgGreen) and a luciferase-based ATP kit were used to assess cellular ATP depletion. Ethanol (100 mm) and POAEE (100 μm) induced a small but irreversible Ca2+ overload response but had no significant effect on PMCA activity. POA (50–100 μm) induced a robust Ca2+ overload, ATP depletion, inhibited PMCA activity, and consequently induced necrosis. Insulin pretreatment (100 nm for 30 min) prevented the POA-induced Ca2+ overload, ATP depletion, inhibition of the PMCA, and necrosis. Moreover, the insulin-mediated protection of the POA-induced Ca2+ overload was partially prevented by the phosphoinositide-3-kinase (PI3K) inhibitor, LY294002. These data provide the first evidence that insulin directly protects pancreatic acinar cell injury induced by bona fide pancreatitis-inducing agents, such as POA. This may have important therapeutic implications for the treatment of pancreatitis. PMID:24993827

  20. Hydrogen peroxide attenuates refilling of intracellular calcium store in mouse pancreatic acinar cells

    PubMed Central

    Yoon, Mi Na; Kim, Dong Kwan; Kim, Se Hoon

    2017-01-01

    Intracellular calcium (Ca2+) oscillation is an initial event in digestive enzyme secretion of pancreatic acinar cells. Reactive oxygen species are known to be associated with a variety of oxidative stress-induced cellular disorders including pancreatitis. In this study, we investigated the effect of hydrogen peroxide (H2O2) on intracellular Ca2+ accumulation in mouse pancreatic acinar cells. Perfusion of H2O2 at 300 µM resulted in additional elevation of intracellular Ca2+ levels and termination of oscillatory Ca2+ signals induced by carbamylcholine (CCh) in the presence of normal extracellular Ca2+. Antioxidants, catalase or DTT, completely prevented H2O2-induced additional Ca2+ increase and termination of Ca2+ oscillation. In Ca2+-free medium, H2O2 still enhanced CCh-induced intracellular Ca2+ levels and thapsigargin (TG) mimicked H2O2-induced cytosolic Ca2+ increase. Furthermore, H2O2-induced elevation of intracellular Ca2+ levels was abolished under sarco/endoplasmic reticulum Ca2+ ATPase-inactivated condition by TG pretreatment with CCh. H2O2 at 300 µM failed to affect store-operated Ca2+ entry or Ca2+ extrusion through plasma membrane. Additionally, ruthenium red, a mitochondrial Ca2+ uniporter blocker, failed to attenuate H2O2-induced intracellular Ca2+ elevation. These results provide evidence that excessive generation of H2O2 in pathological conditions could accumulate intracellular Ca2+ by attenuating refilling of internal Ca2+ stores rather than by inhibiting Ca2+ extrusion to extracellular fluid or enhancing Ca2+ mobilization from extracellular medium in mouse pancreatic acinar cells. PMID:28280417

  1. Hepcidin knockout mice spontaneously develop chronic pancreatitis owing to cytoplasmic iron overload in acinar cells.

    PubMed

    Lunova, Mariia; Schwarz, Peggy; Nuraldeen, Renwar; Levada, Kateryna; Kuscuoglu, Deniz; Stützle, Michael; Vujić Spasić, Maja; Haybaeck, Johannes; Ruchala, Piotr; Jirsa, Milan; Deschemin, Jean-Christophe; Vaulont, Sophie; Trautwein, Christian; Strnad, Pavel

    2017-01-01

    Iron is both an essential and a potentially toxic element, and its systemic homeostasis is controlled by the iron hormone hepcidin. Hepcidin binds to the cellular iron exporter ferroportin, causes its degradation, and thereby diminishes iron uptake from the intestine and the release of iron from macrophages. Given that hepcidin-resistant ferroportin mutant mice show exocrine pancreas dysfunction, we analysed pancreata of aging hepcidin knockout (KO) mice. Hepcidin and Hfe KO mice were compared with wild-type (WT) mice kept on standard or iron-rich diets. Twelve-month-old hepcidin KO mice were subjected to daily minihepcidin PR73 treatment for 1 week. Six-month-old hepcidin KO mice showed cytoplasmic acinar iron overload and mild pancreatitis, together with elevated expression of the iron uptake mediators DMT1 and Zip14. Acinar atrophy, massive macrophage infiltration, fatty changes and pancreas fibrosis were noted in 1-year-old hepcidin KO mice. As an underlying mechanism, 6-month-old hepcidin KO mice showed increased pancreatic oxidative stress, with elevated DNA damage, apoptosis and activated nuclear factor-κB (NF-κB) signalling. Neither iron overload nor pancreatic damage was observed in WT mice fed iron-rich diet or in Hfe KO mice. Minihepcidin application to hepcidin KO mice led to an improvement in general health status and to iron redistribution from acinar cells to macrophages. It also resulted in decreased NF-κB activation and reduced DNA damage. In conclusion, loss of hepcidin signalling in mice leads to iron overload-induced chronic pancreatitis that is not seen in situations with less severe iron accumulation. The observed tissue injury can be reversed by hepcidin supplementation. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  2. Pancreatic panniculitis as a paraneoplastic phenomenon of a pancreatic acinar cell carcinoma.

    PubMed

    Naeyaert, Charlotte; de Clerck, Frederik; De Wilde, Vincent

    2016-12-01

    We present the case of a 59-year-old patient admitted with extreme painful erythematous subcutaneous nodules of the lower extremities in association with arthritis and peripheral eosinophilia. Upon skin biopsy, the diagnosis of pancreatic panniculitis was made. On further investigation, an underlying acinar cell type pancreas carcinoma was revealed. This clinical case does illustrate how a seemingly innocuous skin condition may herald an underlying malignant disease. The presence of pancreatic panniculitis should trigger clinicians to undertake further thorough diagnostic investigation of the pancreas.

  3. Evaluation of Parotid Salivary Glucose Level for Clinical Diagnosis and Monitoring Type 2 Diabetes Mellitus Patients

    PubMed Central

    Wang, Beibei; Du, Juan; Zhu, Zhao; Ma, Zhihong; Wang, Songlin

    2017-01-01

    Background. To investigate the relationships among blood glucose, mixed saliva glucose, and parotid glucose in type 2 diabetes patients and to evaluate the diagnostic and monitoring value of salivary gland glucose in patients with type 2 diabetes (type 2DM). Material and Methods. Thirty patients with type 2DM and 30 healthy age- and sex-matched individuals were included in this study. Glucose levels in unstimulated mixed saliva and in unstimulated parotid saliva were measured by the glucose oxidase peroxidase method. Results. The blood glucose and parotid salivary glucose levels in type 2DM patients were significantly higher than those in the controls (P < 0.05). The blood glucose, parotid salivary glucose, and mixed salivary glucose were 7.46 ± 1.44 mmol/L, 0.18 ± 0.19 mmol/L, and 3.17 × 10−2 ± 2.84 × 10−2 mmol/L, respectively, in the type 2DM group; the corresponding glucose levels in the control group were 5.56 ± 0.71 mmol/L, 7.70 × 10−2 ± 6.02 × 10−2 mmol/L, and 3.47 × 10−2 ± 2.79 × 10−2 mmol/L. The parotid salivary and blood glucose levels in type 2DM patients were strongly correlated; the linear regression equation for blood glucose and parotid salivary glucose was Y = 6.267X + 6.360, with r = 0.810. However, mixed salivary glucose levels were not significantly different in the type 2 diabetes group compared with the control group. Conclusion. Our results suggest that parotid salivary glucose has potential as a biomarker to monitor type 2DM and as a painless, noninvasive method for the management of type 2DM. PMID:28251153

  4. EFFECT OF IRRADIATION ON MICROVASCULAR ENDOTHELIAL CELLS OF PAROTID GLANDS IN THE MINIATURE PIG

    PubMed Central

    Xu, Junji; Yan, Xing; Gao, Runtao; Mao, Lisha; Cotrim, Ana P.; Zheng, Changyu; Zhang, Chunmei; Baum, Bruce J.; Wang, Songlin

    2013-01-01

    Purpose To evaluate the effect of irradiation on microvascular endothelial cells in miniature pig parotid glands. Methods and Materials A single 25-Gy dose of irradiation (IR) was delivered to parotid glands of 6 miniature pigs. Three other animals served as non-IR controls. Local blood flow rate in glands was measured pre- and post-IR with an ultrasonic Doppler analyzer. Samples of parotid gland tissue were taken at 4 h, 24 h, 1 week, and 2 weeks after IR for microvascular density (MVD) analysis and sphingomyelinase (SMase) assay. Histopathology and immunohistochemical staining (anti-CD31 and anti-AQP1) were used to assess morphological changes. MVD was determined by calculating the number of CD31- or AQP1-stained cells per field. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay was used to detect apoptotic cells. The activity of acid and neutral Mg2+-dependent SMase (ASMase and NSMase, respectively) was also assayed. Results Local parotid gland blood flow rate decreased rapidly at 4 h post-IR and remained below control levels throughout the 14-day observation period. Parotid MVD also declined from 4 to 24 hours and remained below control levels thereafter. The activity levels of ASMase and NSMase in parotid glands increased rapidly from 4 to 24 h post-IR and then declined gradually. The frequency of detecting apoptotic nuclei in the glands followed similar kinetics. Conclusions Single-dose IR led to a significant reduction of MVD and local blood flow rate, indicating marked damage to microvascular endothelial cells in miniature pig parotid glands. The significant and rapid increases of ASMase and NSMase activity levels may be important in this IR-induced damage. PMID:20832188

  5. Effect of Irradiation on Microvascular Endothelial Cells of Parotid Glands in the Miniature Pig

    SciTech Connect

    Xu Junji; Yan Xing; Gao Runtao; Mao Lisha; Cotrim, Ana P.; Zheng Changyu; Zhang Chunmei; Baum, Bruce J.; Wang Songlin

    2010-11-01

    Purpose: To evaluate the effect of irradiation on microvascular endothelial cells in miniature pig parotid glands. Methods and Materials: A single 25-Gy dose of irradiation (IR) was delivered to parotid glands of 6 miniature pigs. Three other animals served as non-IR controls. Local blood flow rate in glands was measured pre- and post-IR with an ultrasonic Doppler analyzer. Samples of parotid gland tissue were taken at 4 h, 24 h, 1 week, and 2 weeks after IR for microvascular density (MVD) analysis and sphingomyelinase (SMase) assay. Histopathology and immunohistochemical staining (anti-CD31 and anti-AQP1) were used to assess morphological changes. MVD was determined by calculating the number of CD31- or AQP1-stained cells per field. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay was used to detect apoptotic cells. The activity of acid and neutral Mg{sup 2+}-dependent SMase (ASMase and NSMase, respectively) was also assayed. Results: Local parotid gland blood flow rate decreased rapidly at 4 h post-IR and remained below control levels throughout the 14-day observation period. Parotid MVD also declined from 4 to 24 hours and remained below control levels thereafter. The activity levels of ASMase and NSMase in parotid glands increased rapidly from 4 to 24 h post-IR and then declined gradually. The frequency of detecting apoptotic nuclei in the glands followed similar kinetics. Conclusions: Single-dose IR led to a significant reduction of MVD and local blood flow rate, indicating marked damage to microvascular endothelial cells in miniature pig parotid glands. The significant and rapid increases of ASMase and NSMase activity levels may be important in this IR-induced damage.

  6. Evaluation of Parotid Salivary Glucose Level for Clinical Diagnosis and Monitoring Type 2 Diabetes Mellitus Patients.

    PubMed

    Wang, Beibei; Du, Juan; Zhu, Zhao; Ma, Zhihong; Wang, Songlin; Shan, Zhaochen

    2017-01-01

    Background. To investigate the relationships among blood glucose, mixed saliva glucose, and parotid glucose in type 2 diabetes patients and to evaluate the diagnostic and monitoring value of salivary gland glucose in patients with type 2 diabetes (type 2DM). Material and Methods. Thirty patients with type 2DM and 30 healthy age- and sex-matched individuals were included in this study. Glucose levels in unstimulated mixed saliva and in unstimulated parotid saliva were measured by the glucose oxidase peroxidase method. Results. The blood glucose and parotid salivary glucose levels in type 2DM patients were significantly higher than those in the controls (P < 0.05). The blood glucose, parotid salivary glucose, and mixed salivary glucose were 7.46 ± 1.44 mmol/L, 0.18 ± 0.19 mmol/L, and 3.17 × 10(-2) ± 2.84 × 10(-2) mmol/L, respectively, in the type 2DM group; the corresponding glucose levels in the control group were 5.56 ± 0.71 mmol/L, 7.70 × 10(-2) ± 6.02 × 10(-2) mmol/L, and 3.47 × 10(-2) ± 2.79 × 10(-2) mmol/L. The parotid salivary and blood glucose levels in type 2DM patients were strongly correlated; the linear regression equation for blood glucose and parotid salivary glucose was Y = 6.267X + 6.360, with r = 0.810. However, mixed salivary glucose levels were not significantly different in the type 2 diabetes group compared with the control group. Conclusion. Our results suggest that parotid salivary glucose has potential as a biomarker to monitor type 2DM and as a painless, noninvasive method for the management of type 2DM.

  7. Glycyrrhizin down-regulates CCL2 and CXCL2 expression in cerulein-stimulated pancreatic acinar cells

    PubMed Central

    Panahi, Yaser; Fakhari, Shohreh; Mohammadi, Mehdi; Rahmani, Mohammad Reza; Hakhamaneshi, Mohammad Saeid; Jalili, Ali

    2015-01-01

    Many inflammatory chemokines release from leukocytes and pancreatic acinar cells which play important roles in pathophysiology of acute pancreatitis (AP). Of interests, CXCL2 and CCL2 have been shown elevated in the plasma of patients with AP. We have recently found that Glycyrrhizin (GZ) attenuates AP in mice model. In this study, we aimed to investigate the direct effect of GZ on expression levels of CCL2 and CXCl2 in isolated pancreatic acinar cells. Isolated acinar cells were isolated from the pancreas of healthy C57BL/6 mice, stimulated with cerulein (10-7 M) and then treated with either PBS or different doses of GZ. The levels of CCL2 and CXCL2 expression at mRNA were assessed by qRT-PCR. Conditioned media from supernatants of each cells culture condition were collected for detection of CCL2 and CXCL2 levels by ELISA. First, we observed that cerulein significantly upregulates both cytokines expression in acinar cells. Moreover, we treated the acinar cells with GZ and found that GZ significantly downregulates CCL2 and CXCL2 expression at mRNA levels in a dose-dependent manner. Consistently, the conditioned media of GZ-treated cells contained a significant lower levels of CCL2 and CXCL2 (p<0.05). In conclusion, our data demonstrate for the first time that GZ directly downregulates CCL2 and CXCL2 levels in cerulein-stimulated acinar cells which may explain the mechanism of therapeutic effects of GZ in cerulein-induced AP in mice. PMID:26155433

  8. Hepatitis E Virus in Farmed Rabbits, Wild Rabbits and Petting Farm Rabbits in the Netherlands.

    PubMed

    Burt, Sara A; Veltman, Jorg; Hakze-van der Honing, Renate; Schmitt, Heike; van der Poel, Wim H M

    2016-09-01

    Rabbits have been suggested as a zoonotic source of Hepatitis E virus. Phylogenetic analysis of HEV isolates from farmed, wild and pet rabbits in the Netherlands (23, 0, and 60 % respectively) showed them to be grouped amongst published rabbit HEV sequences and distinct from most human isolates. Dutch rabbits are unlikely to be a zoonotic source.

  9. SERUM SICKNESS IN RABBITS

    PubMed Central

    Fleisher, Mover S.; Jones, Lloyd

    1931-01-01

    1. The injection of a single large dose of normal horse serum into rabbits results in the appearance 3 to 8 days later of erythematous and edematous reactions on the ears in 68.9 per cent of the animals. 2. The injections may be given by any of several routes and reactions appear when the site of injection is definitely distant from the ears. 3. Injections of various antisera into rabbits cause the appearance of similar reactions. 4. These reactions can be considered as manifestations of serum sickness in rabbits. PMID:19869943

  10. Rabbit orthopedic surgery.

    PubMed

    Rich, Gregory A

    2002-01-01

    Orthopedic surgery in rabbits poses several unique parameters for the veterinary surgeon. It is imperative for the veterinarian to be knowledgeable about the anatomic features of the surgical repair site and to become familiar with a rabbit's pain and discomfort often associated with orthopedic injuries. Handling the perioperative and postoperative pain and potential GI disturbances are crucial for a successful outcome of the surgical case. This article is designed to help the veterinary surgeon prepare for the orthopedic surgical procedure and the peripheral physiologic needs of the rabbit from presentation through recovery.

  11. Role of the Accessory Parotid Gland in the Etiology of Parotitis: Statistical Analysis of Sialographic Features.

    PubMed

    Zhu, Wangyong; Hu, Fengchun; Liu, Xingguang; Guo, Songcan; Tao, Qian

    2016-01-01

    This retrospective study aimed to identify if the existence of the accessory parotid gland correlated with the etiology of parotitis. This may aid the development of better treatment strategies in the future. Sialographic features of cases with parotitis and healthy subjects were reviewed. The chi-square test was used to compare the incidence of accessory parotid gland between the groups. The Student's t test was used to compare the length of Stensen's duct, the length from the orifice to the confluence of the accessory duct, and the angle between the accessory duct and Stensen's duct between the groups. The incidence of accessory parotid gland in patients with parotitis was 71.8% (28/39), which was significantly higher than that in healthy subjects (P = 0.005). Patients with parotitis had a longer Stensen's duct than healthy subjects (P = 0.003). There was no significant difference in the length from the orifice to the confluence of the accessory duct or the angle between the accessory duct and Stensen's duct (P = 0.136 and 0.511, respectively) between the groups. The accessory parotid gland might play a role in the pathogenesis of parotitis. The existence of an accessory parotid gland is likely to interfere with salivary flow. Computational fluid dynamics analysis of salivary flow in the ductal system would be useful in future etiologic studies on parotitis.

  12. Actual Dose Variation of Parotid Glands and Spinal Cord for Nasopharyngeal Cancer Patients During Radiotherapy

    SciTech Connect

    Han Chunhui Chen Yijen; Liu An; Schultheiss, Timothy E.; Wong, Jeffrey Y.C.

    2008-03-15

    Purpose: For intensity-modulated radiotherapy of nasopharyngeal cancer, accurate dose delivery is crucial to the success of treatment. This study aimed to evaluate the significance of daily image-guided patient setup corrections and to quantify the parotid gland volume and dose variations for nasopharyngeal cancer patients using helical tomotherapy megavoltage computed tomography (CT). Methods and Materials: Five nasopharyngeal cancer patients who underwent helical tomotherapy were selected retrospectively. Each patient had received 70 Gy in 35 fractions. Daily megavoltage CT scans were registered with the planning CT images to correct the patient setup errors. Contours of the spinal cord and parotid glands were drawn on the megavoltage CT images at fixed treatment intervals. The actual doses delivered to the critical structures were calculated using the helical tomotherapy Planned Adaptive application. Results: The maximal dose to the spinal cord showed a significant increase and greater variation without daily setup corrections. The significant decrease in the parotid gland volume led to a greater median dose in the later phase of treatment. The average parotid gland volume had decreased from 20.5 to 13.2 cm{sup 3} by the end of treatment. On average, the median dose to the parotid glands was 83 cGy and 145 cGy for the first and the last treatment fractions, respectively. Conclusions: Daily image-guided setup corrections can eliminate significant dose variations to critical structures. Constant monitoring of patient anatomic changes and selective replanning should be used during radiotherapy to avoid critical structure complications.

  13. Functional studies of the parotid and pancreas glands in amyotrophic lateral sclerosis.

    PubMed

    Charchaflie, R J; Bustos Fernandez, L; Perec, C J; Gonzalez, E; Marzi, A

    1974-07-01

    Functional studies of the pancreas and parotid glands are reported in 17 patients with amyotrophic lateral sclerosis (ALS). The exocrine function of the pancreas was studied by measuring amylase concentration after stimulation with the endogenous secretin-pancreozymine test (ESP). Under these conditions, the pancreatic amylase concentration in ALS patients was found to be markedly decreased by about 45% when compared with those of healthy control subjects. Different conclusions in the literature about a possible impairment of the exocrine pancreas in ALS patients induced us to study the function of the parotid gland, which has close structural, functional, and physiopathological relationship with the pancreas. Flow rate and bicarbonate concentration of parotid saliva were measured after indirect stimulation (intraoral citric acid) and direct stimulation (pilocarpine). After indirect stimulation, both parotid flow rate and bicarbonate concentration from ALS patients were found to be decreased by about 66% and 70% respectively, when compared with controls. On the other hand, direct stimulation with pilocarpine in ALS patients elicited normal responses in both flow rate and bicarbonate concentration of saliva. It is concluded that the pancreatic and parotid deficiencies observed in ALS patients do not indicate primary disease of these exocrine glands. This interpretation is further emphasized by the results obtained by a sweat test, plasma osmolarity, and sialographic studies. The possibility that the gland impairments observed might be due to modifications of the neuroendocrine mechanisms regulating their secretory activity is suggested.

  14. Functional studies of the parotid and pancreas glands in amyotrophic lateral sclerosis

    PubMed Central

    Charchaflie, R. J.; Fernandez, L. Bustos; Perec, C. J.; Gonzalez, E.; Marzi, A.

    1974-01-01

    Functional studies of the pancreas and parotid glands are reported in 17 patients with amyotrophic lateral sclerosis (ALS). The exocrine function of the pancreas was studied by measuring amylase concentration after stimulation with the endogenous secretin-pancreozymine test (ESP). Under these conditions, the pancreatic amylase concentration in ALS patients was found to be markedly decreased by about 45% when compared with those of healthy control subjects. Different conclusions in the literature about a possible impairment of the exocrine pancreas in ALS patients induced us to study the function of the parotid gland, which has close structural, functional, and physiopathological relationship with the pancreas. Flow rate and bicarbonate concentration of parotid saliva were measured after indirect stimulation (intraoral citric acid) and direct stimulation (pilocarpine). After indirect stimulation, both parotid flow rate and bicarbonate concentration from ALS patients were found to be decreased by about 66% and 70% respectively, when compared with controls. On the other hand, direct stimulation with pilocarpine in ALS patients elicited normal responses in both flow rate and bicarbonate concentration of saliva. It is concluded that the pancreatic and parotid deficiencies observed in ALS patients do not indicate primary disease of these exocrine glands. This interpretation is further emphasized by the results obtained by a sweat test, plasma osmolarity, and sialographic studies. The possibility that the gland impairments observed might be due to modifications of the neuroendocrine mechanisms regulating their secretory activity is suggested. PMID:4852110

  15. Diffusion weighted magnetic resonance imaging in the diagnosis of parotid masses. Preliminary results

    PubMed Central

    Yologlu, Zeynel; Aydin, Hasan; Alp, Nalan A.; Aribas, Bilgin K.; Kizilgoz, Volkan; Arda, Kemal

    2016-01-01

    Objective To demonstrate the diagnostic potentials of MRI, diffusion weighted imaging (DWI), and apparent diffusion coefficient (ADC) mapping in the detection of parotid masses correlated to the histopathological results. Methods Study design was retrospective. Fifteen patients with parotid gland masses were included as the study group and contralateral normal parotis glands of same patients were taken as the control group. Patients with bilateral parotid gland tumors were excluded, 7 right-sided and 8 left-sided parotid masses were included in the research. The study took place at the Department of Radiology, Ankara, Turkey, between May 2012 and September 2014. Results Apparent diffusion coefficient measurements of 15 parotis tumors in 1000 and 750 sec/mm2 b-values with comparison to the contralateral normal gland parenchyma were demonstrated. Neurofibromas was predicted as the highest, and lipomas as the lowest ADC values. Pleomorphic adenomas, Warthin’s tumor, and normal parotid parenchyma indicate significant statistical differences from each other on the basis of mean ADC values (p<0.05). Conclusion The DWI and ADC mapping of parotis gland could aid in the differential diagnosis of benign and malignant masses. PMID:27874161

  16. Minimally-invasive surgery in the management of symptomatic parotid stones.

    PubMed

    Samani, Meera; Hills, Alexander James; Holden, Adam Matthew; Man, Chang-Bon; McGurk, Mark

    2016-05-01

    Traditionally, large, symptomatic, parotid stones that were refractory to conservative treatment were usually managed by parotidectomy, with the attendant risk to the facial nerve. Microendoscopes have transformed the management of such stones. For large stones that are not amenable to retrieval with a basket the endoscope provides a new dimension to operative surgery. It can guide the surgeon on to the duct and stone without the need to remove the parotid gland. In 2005-2014, 111 consecutive patients underwent endoscopically-assisted operations for the removal of 132 parotid stones at Guy's Hospital. Removal was successful in all but three cases. Long-term follow up (mean (SD) 44 (30) months) was obtained by postal or online survey and telephone, and 92 patients (83%) said that they had no symptoms. Further endoscope-assisted surgery was required in four cases, with preservation of the gland in all patients. Sialocoeles developed postoperatively in 15% (n=17). Transient facial nerve weakness occurred in 4 cases (4%), and there was no case of permanent deficit. Endoscopically-assisted retrieval of parotid stones is a technique to preserve the gland that adds to the current minimally-invasive options for management of parotid calculi.

  17. Role of the Accessory Parotid Gland in the Etiology of Parotitis: Statistical Analysis of Sialographic Features

    PubMed Central

    Zhu, Wangyong; Hu, Fengchun; Liu, Xingguang; Guo, Songcan; Tao, Qian

    2016-01-01

    This retrospective study aimed to identify if the existence of the accessory parotid gland correlated with the etiology of parotitis. This may aid the development of better treatment strategies in the future. Sialographic features of cases with parotitis and healthy subjects were reviewed. The chi-square test was used to compare the incidence of accessory parotid gland between the groups. The Student’s t test was used to compare the length of Stensen’s duct, the length from the orifice to the confluence of the accessory duct, and the angle between the accessory duct and Stensen’s duct between the groups. The incidence of accessory parotid gland in patients with parotitis was 71.8% (28/39), which was significantly higher than that in healthy subjects (P = 0.005). Patients with parotitis had a longer Stensen’s duct than healthy subjects (P = 0.003). There was no significant difference in the length from the orifice to the confluence of the accessory duct or the angle between the accessory duct and Stensen’s duct (P = 0.136 and 0.511, respectively) between the groups. The accessory parotid gland might play a role in the pathogenesis of parotitis. The existence of an accessory parotid gland is likely to interfere with salivary flow. Computational fluid dynamics analysis of salivary flow in the ductal system would be useful in future etiologic studies on parotitis. PMID:26913509

  18. [Pleomorphic adenoma of the parotid gland, rules for resection].

    PubMed

    de Ridder, Mischa; Smeele, Ludi E; Balm, Alfons J M

    2012-01-01

    The importance of complete excision of a benign pleomorphic adenoma is illustrated by two patients' histories. A 28-year-old man underwent a local excision of a nodule under the left ear without histological confirmation. Ten years later he returned to our institute with a large multilocular process and subcutaneous nodules. Cytology showed pleomorphic adenoma. Patient was treated with total facial nerve preserving parotidectomy and radiotherapy. An 81-year-old male underwent a surgical removal of a swelling under his left ear eight years before admission for a large diffusely infiltrating tumor in the neck. Repeated cytology showed carcinoma ex pleomorphic adenoma. This tumor was inoperable and he was treated by palliative irradiation. In case of incomplete resection, pleomorphic adenoma cells are spilled with an increasing chance of local recurrence. Also degeneration into carcinoma ex pleomorphic adenoma is possible after incomplete resection, with impact on survival. These risks of residual disease determine the need of centralization of diagnosis and treatment of this benign parotid tumor.

  19. Bromoenol lactone enhances the permeabilization of rat submandibular acinar cells by P2X7 agonists

    PubMed Central

    Chaïb, N; Kabré, E; Alzola, E; Pochet, S; Dehaye, J P

    2000-01-01

    The permeabilizing effect of P2X7 agonists was tested in rat submandibular acinar cells using the uptake of ethidium bromide as an index. The uptake of ethidium bromide by acini incubated at 37°C in the presence of 1 mM ATP increased with time and reached after 5 min about 10% of maximal uptake measured in the presence of digitonin. The response to ATP was dose-dependent (half-maximal concentration around 40 μM) and it was decreased when the temperature was lowered to 25°C. Benzoyl-ATP reproduced the response to ATP (half-maximal concentration around 10 μM). UTP or 2-methylthioATP had no effect. The permeabilization in response to ATP was blocked by oxidized ATP and by magnesium and inhibited by Coomassie blue. ATP increased the activity of a calcium-insensitive phospholipase A2 (iPLA2). Bromoenol lactone (BEL) inhibited the iPLA2 stimulated by ATP but potentiated the uptake of ethidium bromide in response to the purinergic agonist. From these results it is concluded that the activation of P2X7 receptors permeabilizes rat submandibular acinar cells. The pore-forming activity of the receptor might be negatively regulated by the concomitant activation of the iPLA2 by the receptor. PMID:10683195

  20. Valproic Acid Limits Pancreatic Recovery after Pancreatitis by Inhibiting Histone Deacetylases and Preventing Acinar Redifferentiation Programs.

    PubMed

    Eisses, John F; Criscimanna, Angela; Dionise, Zachary R; Orabi, Abrahim I; Javed, Tanveer A; Sarwar, Sheharyar; Jin, Shunqian; Zhou, Lili; Singh, Sucha; Poddar, Minakshi; Davis, Amy W; Tosun, Akif Burak; Ozolek, John A; Lowe, Mark E; Monga, Satdarshan P; Rohde, Gustavo K; Esni, Farzad; Husain, Sohail Z

    2015-12-01

    The mechanisms by which drugs induce pancreatitis are unknown. A definite cause of pancreatitis is due to the antiepileptic drug valproic acid (VPA). On the basis of three crucial observations-that VPA inhibits histone deacetylases (HDACs), HDACs mediate pancreas development, and aspects of pancreas development are recapitulated during recovery of the pancreas after injury-we hypothesized that VPA does not cause injury on its own, but it predisposes patients to pancreatitis by inhibiting HDACs and provoking an imbalance in pancreatic recovery. In an experimental model of pancreatic injury, we found that VPA delayed recovery of the pancreas and reduced acinar cell proliferation. In addition, pancreatic expression of class I HDACs (which are the primary VPA targets) increased in the midphase of pancreatic recovery. VPA administration inhibited pancreatic HDAC activity and led to the persistence of acinar-to-ductal metaplastic complexes, with prolonged Sox9 expression and sustained β-catenin nuclear activation, findings that characterize a delay in regenerative reprogramming. These effects were not observed with valpromide, an analog of VPA that lacks HDAC inhibition. This is the first report, to our knowledge, that VPA shifts the balance toward pancreatic injury and pancreatitis through HDAC inhibition. The work also identifies a new paradigm for therapies that could exploit epigenetic reprogramming to enhance pancreatic recovery and disorders of pancreatic injury.

  1. An implication of novel methodology to study pancreatic acinar mitochondria under in situ conditions.

    PubMed

    Manko, Bohdan O; Klevets, Myron Yu; Manko, Volodymyr V

    2013-03-01

    Mitochondria maintain numerous energy-consuming processes in pancreatic acinar cells, yet characteristics of pancreatic mitochondrial oxidative phosphorylation in native conditions are poorly studied. Besides, it is not known which type of solution is most adequate to preserve functions of pancreatic mitochondria in situ. Here we propose a novel experimental protocol suitable for in situ analysis of pancreatic mitochondria metabolic states. Isolated rat pancreatic acini were permeabilized with low doses of digitonin. Different metabolic states of mitochondria were examined in KCl- and sucrose-based solutions using Clark oxygen electrode. Respiration of digitonin-treated, unlike of intact, acini was substantially intensified by succinate or mixture of pyruvate plus malate. Substrate-stimulated respiration rate did not depend on solution composition. In sucrose-based solution, oligomycin inhibited State 3 respiration at succinate oxidation by 65.4% and at pyruvate plus malate oxidation by 60.2%, whereas in KCl-based solution, by 32.0% and 36.1%, respectively. Apparent respiratory control indices were considerably higher in sucrose-based solution. Rotenone or thenoyltrifluoroacetone severely inhibited respiration, stimulated by pyruvate plus malate or succinate, respectively. This revealed low levels of non-mitochondrial oxygen consumption of permeabilized acinar cells. These results suggest a stronger coupling between respiration and oxidative phosphorylation in sucrose-based solution.

  2. The role of Ca2+ influx in endocytic vacuole formation in pancreatic acinar cells

    PubMed Central

    Voronina, Svetlana; Collier, David; Chvanov, Michael; Middlehurst, Ben; Beckett, Alison J.; Prior, Ian A.; Criddle, David N.; Begg, Malcolm; Mikoshiba, Katsuhiko; Sutton, Robert; Tepikin, Alexei V.

    2014-01-01

    The inducers of acute pancreatitis trigger a prolonged increase in the cytosolic Ca2+ concentration ([Ca2+]c), which is responsible for the damage to and eventual death of pancreatic acinar cells. Vacuolization is an important indicator of pancreatic acinar cell damage. Furthermore, activation of trypsinogen occurs in the endocytic vacuoles; therefore the vacuoles can be considered as ‘initiating’ organelles in the development of the cell injury. In the present study, we investigated the relationship between the formation of endocytic vacuoles and Ca2+ influx developed in response to the inducers of acute pancreatitis [bile acid taurolithocholic acid 3-sulfate (TLC-S) and supramaximal concentration of cholecystokinin-8 (CCK)]. We found that the inhibitor of STIM (stromal interaction molecule)/Orai channels, GSK-7975A, effectively suppressed both the Ca2+ influx (stimulated by inducers of pancreatitis) and the formation of endocytic vacuoles. Cell death induced by TLC-S or CCK was also inhibited by GSK-7975A. We documented the formation of endocytic vacuoles in response to store-operated Ca2+ entry (SOCE) induced by thapsigargin [TG; inhibitor of sarcoplasmic/endoplasmic reticulum (ER) Ca2+ pumps] and observed strong inhibition of TG-induced vacuole formation by GSK-7975A. Finally, we found that structurally-unrelated inhibitors of calpain suppress formation of endocytic vacuoles, suggesting that this Ca2+-dependent protease is a mediator between Ca2+ elevation and endocytic vacuole formation. PMID:25370603

  3. The econobiology of pancreatic acinar cells granule inventory and the stealthy nano-machine behind it.

    PubMed

    Hammel, Ilan; Meilijson, Isaac

    2016-03-01

    The pancreatic gland secretes most of the enzymes and many other macromolecules needed for food digestion in the gastrointestinal tract. These molecules play an important role in digestion, host defense and lubrication. The secretion of pancreatic proteins ensures the availability of the correct mix of proteins when needed. This review describes model systems available for the study of the econobiology of secretory granule content. The secretory pancreatic molecules are stored in large dense-core secretory granules that may undergo either constitutive or evoked secretion, and constitute the granule inventory of the cell. It is proposed that the Golgi complex functions as a distribution center for secretory proteins in pancreatic acinar cells, packing the newly formed secretory molecules into maturing secretory granules, also known functionally as condensing vacuoles. Mathematical modelling brings forward a process underlying granule inventory maintenance at various physiological states of condensation and aggregation by homotypic fusion. These models suggest unique but simple mechanisms accountable for inventory buildup and size, as well as for the distribution of secretory molecules into different secretory pathways in pancreatic acinar cells.

  4. Restricted diffusion in a model acinar labyrinth by NMR: Theoretical and numerical results

    NASA Astrophysics Data System (ADS)

    Grebenkov, D. S.; Guillot, G.; Sapoval, B.

    2007-01-01

    A branched geometrical structure of the mammal lungs is known to be crucial for rapid access of oxygen to blood. But an important pulmonary disease like emphysema results in partial destruction of the alveolar tissue and enlargement of the distal airspaces, which may reduce the total oxygen transfer. This effect has been intensively studied during the last decade by MRI of hyperpolarized gases like helium-3. The relation between geometry and signal attenuation remained obscure due to a lack of realistic geometrical model of the acinar morphology. In this paper, we use Monte Carlo simulations of restricted diffusion in a realistic model acinus to compute the signal attenuation in a diffusion-weighted NMR experiment. We demonstrate that this technique should be sensitive to destruction of the branched structure: partial removal of the interalveolar tissue creates loops in the tree-like acinar architecture that enhance diffusive motion and the consequent signal attenuation. The role of the local geometry and related practical applications are discussed.

  5. Valproic Acid Limits Pancreatic Recovery after Pancreatitis by Inhibiting Histone Deacetylases and Preventing Acinar Redifferentiation Programs

    PubMed Central

    Eisses, John F.; Criscimanna, Angela; Dionise, Zachary R.; Orabi, Abrahim I.; Javed, Tanveer A.; Sarwar, Sheharyar; Jin, Shunqian; Zhou, Lili; Singh, Sucha; Poddar, Minakshi; Davis, Amy W.; Tosun, Akif Burak; Ozolek, John A.; Lowe, Mark E.; Monga, Satdarshan P.; Rohde, Gustavo K.; Esni, Farzad; Husain, Sohail Z.

    2016-01-01

    The mechanisms by which drugs induce pancreatitis are unknown. A definite cause of pancreatitis is due to the antiepileptic drug valproic acid (VPA). On the basis of three crucial observations—that VPA inhibits histone deacetylases (HDACs), HDACs mediate pancreas development, and aspects of pancreas development are recapitulated during recovery of the pancreas after injury—we hypothesized that VPA does not cause injury on its own, but it predisposes patients to pancreatitis by inhibiting HDACs and provoking an imbalance in pancreatic recovery. In an experimental model of pancreatic injury, we found that VPA delayed recovery of the pancreas and reduced acinar cell proliferation. In addition, pancreatic expression of class I HDACs (which are the primary VPA targets) increased in the midphase of pancreatic recovery. VPA administration inhibited pancreatic HDAC activity and led to the persistence of acinar-to-ductal metaplastic complexes, with prolonged Sox9 expression and sustained β-catenin nuclear activation, findings that characterize a delay in regenerative reprogramming. These effects were not observed with valpromide, an analog of VPA that lacks HDAC inhibition. This is the first report, to our knowledge, that VPA shifts the balance toward pancreatic injury and pancreatitis through HDAC inhibition. The work also identifies a new paradigm for therapies that could exploit epigenetic reprogramming to enhance pancreatic recovery and disorders of pancreatic injury. PMID:26476347

  6. Salivary gland acinar cells regenerate functional glandular structures in modified hydrogels

    NASA Astrophysics Data System (ADS)

    Pradhan, Swati

    Xerostomia, a condition resulting from irradiation of the head and neck, affects over 40,000 cancer patients each year in the United States. Direct radiation damage of the acinar cells that secrete fluid and protein results in salivary gland hypofunction. Present medical management for xerostomia for patients treated for upper respiratory cancer is largely ineffective. Patients who have survived their terminal diagnosis are often left with a diminished quality of life and are unable to enjoy the simple pleasures of eating and drinking. This project aims to ultimately reduce human suffering by developing a functional implantable artificial salivary gland. The goal was to create an extracellular matrix (ECM) modified hyaluronic acid (HA) based hydrogel culture system that allows for the growth and differentiation of salivary acinar cells into functional acini-like structures capable of secreting large amounts of protein and fluid unidirectionally and to ultimately engineer a functional artificial salivary gland that can be implanted into an animal model. A tissue collection protocol was established and salivary gland tissue was obtained from patients undergoing head and neck surgery. The tissue specimen was assessed by histology and immunohistochemistry to establish the phenotype of normal salivary gland cells including the native basement membranes. Hematoxylin and eosin staining confirmed normal glandular tissue structures including intercalated ducts, striated ducts and acini. alpha-Amylase and periodic acid schiff stain, used for structures with a high proportion of carbohydrate macromolecules, preferentially stained acinar cells in the tissue. Intercalated and striated duct structures were identified using cytokeratins 19 and 7 staining. Myoepithelial cells positive for cytokeratin 14 were found wrapped around the serous and mucous acini. Tight junction components including ZO-1 and E-cadherin were present between both ductal and acinar cells. Ductal and acinar

  7. [Two cases of anesthesia mumps in the upper parotid gland after general anesthesia in the lateral position].

    PubMed

    Adachi, Yushi; Suzuki, Katsumi; Itagaki, Taiga; Obata, Yukako; Doi, Matsuyuki; Sato, Shigehito

    2008-09-01

    We describe two cases of acute transient swelling of the upper side of parotid glands of the patients after general anesthesia in the lateral position. The serum amylase levels in the patients were not increased and the enlargement of the parotid gland was diagnosed as anesthesia mumps. Previous reports suggested that mechanical compression might produce the swelling of the secreting organ, but our patients showed temporal parotid enlargement in the upper free side. Although, pre-medication with atropine might become a cause of parotid gland swelling, we anesthetized these patients without anti-cholinergic drugs. Procedures of oro-tracheal intubation and stimuli of endotracheal tube may induce impairment of the normal flow of saliva and lead to enlargement of the parotid gland.

  8. Giant pleomorphic adenoma of the parotid gland: an unusual case presentation and literature review.

    PubMed

    Tarsitano, A; Pizzigallo, A; Giorgini, F; Marchetti, C

    2015-10-01

    Pleomorphic adenoma is the most common type of all salivary gland tumours. Although uncommon, cases of giant pleomorphic adenomas have been described in the medical literature, the majority involving the parotid gland. This paper describes an unusual case of a giant adenoma arising in the parotid gland. The patient underwent surgical resection of the giant tumour, which was one of the largest pleomorphic adenoma reported in recent literature. This case has prompted us to evaluate the behaviour of those benign tumours, which suggested that aesthetic and social morbidity is sufficient to justify, when possible, early tumour excision, despite the relatively low risk of malignant transformation. Management of this unusual tumour is discussed, and the literature on giant parotid tumours is reviewed.

  9. Primary clear cell carcinoma of parotid gland: Case report and review of literature

    PubMed Central

    Rodríguez, Marta Saldaña; Reija, Maria Fe García; Rodilla, Irene González

    2013-01-01

    Clear cell carcinoma (CCC) is a rare low-grade carcinoma that represents only 1% to 2% of all salivary glands tumors. The finding of a clear cell tumor in a parotid gland involves the necessity of differential diagnosis between primary clear cell parotid tumors and metastases, mainly from kidney. The biological behavior is not very aggressive and development, which is very slow, is usually asymptomatic and indeed, the tumor often reaches considerable dimensions before being diagnosed. The treatment of choice is the surgical excision. There are rare cases of local recurrence and distant metastases. The aim of this article is to report a primary CCC in the parotid gland that microscopically closely resembled a metastatic CCC of renal origin, making microscopic differentiation difficult. PMID:23798840

  10. Primary clear cell carcinoma of parotid gland: Case report and review of literature.

    PubMed

    Rodríguez, Marta Saldaña; Reija, Maria Fe García; Rodilla, Irene González

    2013-01-01

    Clear cell carcinoma (CCC) is a rare low-grade carcinoma that represents only 1% to 2% of all salivary glands tumors. The finding of a clear cell tumor in a parotid gland involves the necessity of differential diagnosis between primary clear cell parotid tumors and metastases, mainly from kidney. The biological behavior is not very aggressive and development, which is very slow, is usually asymptomatic and indeed, the tumor often reaches considerable dimensions before being diagnosed. The treatment of choice is the surgical excision. There are rare cases of local recurrence and distant metastases. The aim of this article is to report a primary CCC in the parotid gland that microscopically closely resembled a metastatic CCC of renal origin, making microscopic differentiation difficult.

  11. Sonoelastography – A Useful Adjunct for Parotid Gland Ultrasound Assessment in Patients Suffering from Chronic Inflammation

    PubMed Central

    Wierzbicka, Małgorzata; Kałużny, Jarosław; Ruchała, Marek; Stajgis, Marek; Kopeć, Tomasz; Szyfter, Witold

    2014-01-01

    Background Shear wave elastography (SWE) is widely used in breast, liver, prostate and thyroid evaluations. Elastography provides additional information if used to assess parotid gland pathology. We assessed parotid glands by means of SWE to compare the parenchyma properties in different types of inflammation. Material/Methods Prospective analysis included 78 consecutive patients with parotid gland pathology: sialolithiasis (33), Stensen’s duct stenosis (15), chronic inflammation (10), and primary Sjögren syndrome (pSS) (20) treated at the Department of Otolaryngology, Head and Neck Surgery of PUMS. The primary predictor variable was type of parotid pathology, and secondary predictor variables were patient age and the duration and intensity of complaints. Ultrasound pictures were compared with elastography values of parotid parenchyma. Results Mean elasticity values for pSS (111 Kilopascals (kPa), Stensen’s duct stenosis (63 kPa), sialolithiasis (82 kPa), and chronic inflammation (77 kPa) were significantly higher than the mean value for healthy patients (24 kPa). Elasticity increased proportionally to the intensity of complaints: mild (51 kPa), moderate (78 kPa), and strong (90 kPa). Increased elasticity did not correspond with ultrasonographic pictures. In pSS the parenchyma was almost twice as stiff as in chronic inflammation (p=0.02), although subjective complaints were mostly mild or moderate, and the ultrasonographic picture did not present features of fibrosis. Conclusions Sonoelastography, by improving routine ultrasonographic assessment, might be a useful tool for parotid evaluations during the course of chronic inflammation. An extraordinarily high degree of stiffness was revealed in pSS despite lack of fibrosis by ultrasonography and moderate subjective complaints, suggesting that sonoelastography could be a valuable diagnostic tool. PMID:25398237

  12. Volume effects and region-dependent radiosensitivity of the parotid gland

    SciTech Connect

    Konings, Antonius W.T. . E-mail: a.w.t.konings@med.rug.nl; Cotteleer, Femmy; Faber, Hette; Luijk, Peter van; Meertens, Harm; Coppes, Rob P.

    2005-07-15

    Purpose: To detect volume effects and possible regional differences in radiosensitivity of the rat parotid gland. Methods and Materials: Parotid glands of male albino Wistar rats were locally X-irradiated, with collimators with conformal radiation portals used to supply 100% volume and 50% cranial/caudal partial volumes. High-resolution magnetic resonance imaging was used to provide the outlines of the parotid glands. Single doses of up to 40 Gy were applied, and the effects on saliva secretion, measured with the aid of miniaturized Lashley cups, were followed up to 365 days after the irradiation. Results: Under conditions of equal mean absorbed doses and small variations in dose distribution, a pertinent volume effect was observed for late but not for early radiation damage. The late effects were different for the cranial part as compared with the caudal part of the parotid gland. The reduction in flow rate was much more severe after irradiation in the cranial part. After a single dose of 30 Gy, the reductions in flow rates were approximately 65% and 25% for the cranial and caudal parts, respectively. At that dose, no saliva flow was observed after irradiation of 100% of the gland. Conclusion: From the rat model studies presented, it is concluded that late radiation damage after partial irradiation of parotid glands shows region-dependent volume effects. This finding is expected to be relevant to the radiosensitivity of human salivary glands, and it implies that the predictive power of the mean dose concept in radiotherapeutic practice is limited. The finding of region-dependent late radiation damage also challenges the basic assumptions of most current normal tissue complication probability models for parotid gland function.

  13. A modified device for long term sampling of parotid saliva in various experimental conditions.

    PubMed

    Takayanagi, A; Nomura, T; Yamanaka, S; Takaesu, Y

    1995-05-01

    A parotid cup has been widely used as an intraoral device for the collection of parotid saliva. However, in long duration sampling, the cup tends to disconnect under circumstances such as mastication, sleep or physical exercise. We have designed a modified device of parotid cup for saliva collection to overcome these unfavorable conditions. The parotid cup was modified by fixing it to the bite-plate appliance which was adjusted individually to the occlusal plane in order to avoid disconnection of the cup under varying conditions. Using this device, we could measure salivary flow rate during mastication, sleep or physical exercise. Additional advantages of this device are that it is easy to make with acrylic resin and is inexpensive. The preliminary study using this device showed that flow rates of unstimulated parotid saliva varied from 0.06 +/- 0.04 ml/min. to 0.16 +/- 0.10 ml/min. (mean +/- s.d) from 7 a.m. to 12 p.m. in 7 subjects. In five subjects, the flow rate of parotid saliva during meal (lunch) was much higher than that of resting on a chair, playing table tennis, or sleeping at night for 6-8 hours. This might be considered due to the stimuli of the meal content. Flow rates of saliva were also examined with various stimuli. The results showed that salty pickled plum > sour lemon juice > 10% ascorbic acid > sweet milky candy > 1% ascorbic acid. These data suggest that our modified device is useful for various experiments in salivary research.

  14. Epiplakin deficiency aggravates murine caerulein-induced acute pancreatitis and favors the formation of acinar keratin granules.

    PubMed

    Wögenstein, Karl L; Szabo, Sandra; Lunova, Mariia; Wiche, Gerhard; Haybaeck, Johannes; Strnad, Pavel; Boor, Peter; Wagner, Martin; Fuchs, Peter

    2014-01-01

    Epiplakin, a member of the plakin protein family, is exclusively expressed in epithelial tissues and was shown to bind to keratins. Epiplakin-deficient (EPPK-/-) mice showed no obvious spontaneous phenotype, however, EPPK-/- keratinocytes displayed faster keratin network breakdown in response to stress. The role of epiplakin in pancreas, a tissue with abundant keratin expression, was not yet known. We analyzed epiplakin's expression in healthy and inflamed pancreatic tissue and compared wild-type and EPPK-/- mice during caerulein-induced acute pancreatitis. We found that epiplakin was expressed primarily in ductal cells of the pancreas and colocalized with apicolateral keratin bundles in murine pancreatic acinar cells. Epiplakin's diffuse subcellular localization in keratin filament-free acini of K8-deficient mice indicated that its filament-associated localization in acinar cells completely depends on its binding partner keratin. During acute pancreatitis, epiplakin was upregulated in acinar cells and its redistribution closely paralleled keratin reorganization. EPPK-/- mice suffered from aggravated pancreatitis but showed no obvious regeneration phenotype. At the most severe stage of the disease, EPPK-/- acinar cells displayed more keratin aggregates than those of wild-type mice. Our data propose epiplakin to be a protective protein during acute pancreatitis, and that its loss causes impaired disease-associated keratin reorganization.

  15. Variations in the expression and distribution pattern of AQP5 in acinar cells of patients with sialadenosis.

    PubMed

    Teymoortash, Afshin; Wiegand, Susanne; Borkeloh, Martin; Bette, Michael; Ramaswamy, Annette; Steinbach-Hundt, Silke; Neff, Andreas; Werner, Jochen A; Mandic, Robert

    2012-01-01

    Previously, we pointed out on a possible role of aquaporin 5 (AQP5) in the development of sialadenosis. The goal of the present study was to further assess the association of AQP5 in the development of this salivary gland disease. The acinar diameter and mean surface area appeared elevated in sialadenosis tissues, which is a typical observation in this disease. AQP5 expression was evaluated by immunohistochemistry using tissue samples derived from salivary glands of patients with confirmed sialadenosis either as a primary diagnosis or as a secondary diagnosis within the framework of other salivary gland diseases. Normal salivary gland tissue served as a control. In sialadenosis tissues, the AQP5 signal at the apical plasma membrane of acinar cells frequently appeared stronger compared with that in normal salivary glands. In addition, the distribution of AQP5 at the apical region seemed to differ between normal and sialadenosis tissues, where AQP5 frequently was diffusely distributed near or at the apical plasma membrane of the acinar cells in contrast to normal controls where the AQP5 signal was strictly confined to the apical plasma membrane. These observations suggest that sialadenosis is associated with a different AQP5 expression and distribution pattern in salivary acinar cells.

  16. The relation between apoptosis of acinar cells and nitric oxide during acute rejection of pancreas transplantation in rats.

    PubMed

    Xiaoguang, Ni; Zhong, Liu; Hailong, Chen; Ping, Zhao; Xiaofeng, Bai; Fenglin, Guan

    2003-01-01

    Apoptosis is an important mechanism of immune-mediated graft damage. Nitric oxide (NO) generated by inducible NO synthase (iNOS) has been demonstrated to induce apoptosis. This study investigated whether apoptosis occurs during pancreas allograft rejection and examined the relationship of apoptosis of acinar cells and NO. The rats were divided into three groups: untreated isograft group, untreated allograft group and aminoguanidine (AG)-treated group. The pancreatic grafts were harvested on the post-transplantation day 3, 5 and 7 and were used to detect the histopathological rejection grade, the expression of iNOS and the apoptotic index (AI) of the graft. iNOS presented faint positive in the acinar cells of untreated isografts and did not change greatly after transplantation (P>0.05), the level of iNOS in the untreated allografts increased progressively (P<0.01) and at the same time point was significantly higher than that of untreated isograft group and AG-treated group (P<0.01). The transferase-mediated dUTP nick end labeling showed that the apoptotic cells were mainly acinar cells. A significant correlation between AI and iNOS was noted (P<0.01, r=0.611). Therefore, NO-mediated apoptosis of acinar cells plays an important role in acute rejection of pancreas transplantation, AG can mitigate the damage of pancreas allografts.

  17. Sulforaphane Protects Pancreatic Acinar Cell Injury by Modulating Nrf2-Mediated Oxidative Stress and NLRP3 Inflammatory Pathway

    PubMed Central

    Dong, Zhaojun; Shang, Haixiao; Chen, Yong Q.; Pan, Li-Long

    2016-01-01

    Acute pancreatitis (AP) is characterized by early activation of intra-acinar proteases followed by acinar cell death and inflammation. Cellular oxidative stress is a key mechanism underlying these pathological events. Sulforaphane (SFN) is a natural organosulfur antioxidant with undescribed effects on AP. Here we investigated modulatory effects of SFN on cellular oxidation and inflammation in AP. AP was induced by cerulean hyperstimulation in BALB/c mice. Treatment group received a single dose of 5 mg/kg SFN for 3 consecutive days before AP. We found that SFN administration attenuated pancreatic injury as evidenced by serum amylase, pancreatic edema, and myeloperoxidase, as well as by histological examination. SFN administration reverted AP-associated dysregulation of oxidative stress markers including pancreatic malondialdehyde and redox enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). In acinar cells, SFN treatment upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and Nrf2-regulated redox genes including quinoneoxidoreductase-1, heme oxidase-1, SOD1, and GPx1. In addition, SFN selectively suppressed cerulein-induced activation of the nucleotide-binding domain leucine-rich repeat containing family, pyrin domain-containing 3 (NLRP3) inflammasome, in parallel with reduced nuclear factor- (NF-) κB activation and modulated NF-κB-responsive cytokine expression. Together, our data suggested that SFN modulates Nrf2-mediated oxidative stress and NLRP3/NF-κB inflammatory pathways in acinar cells, thereby protecting against AP. PMID:27847555

  18. Parotid Gland Sparing With Helical Tomotherapy in Head-and-Neck Cancer

    SciTech Connect

    Voordeckers, Mia; Farrag, Ashraf; Everaert, Hendrik; Tournel, Koen; Storme, Guy; Verellen, Dirk; De Ridder, Mark

    2012-10-01

    Purpose: This study evaluated the ability of helical tomotherapy to spare the function of the parotid glands in patients with head-and-neck cancer by analyzing dose-volume histograms, salivary gland scintigraphy, and quality of life assessment. Methods and Materials: Data from 76 consecutive patients treated with helical tomotherapy (Hi-Art Tomotherapy) at University Hospital Brussel were analyzed. During planning, priority was given to planning target volume (PTV) coverage: {>=}95% of the dose must be delivered to {>=}95% of the PTV. Elective nodal regions received 54 Gy (1.8 Gy/fraction). A dose of 70.5 Gy (2.35 Gy/fraction) was prescribed to the primary tumor and pathologic lymph nodes (simultaneous integrated boost scheme). Objective scoring of salivary excretion was performed by salivary gland scintigraphy. Subjective scoring of salivary gland function was evaluated by the European Organization for Research and Treatment of Cancer quality of life questionnaires Quality of Life Questionnaire-C30 (QLQ-C30) and Quality of Life Questionnaire-Head and Neck 35 (H and N35). Results: Analysis of dose-volume histograms (DVHs) showed excellent coverage of the PTV. The volume of PTV receiving 95% of the prescribed dose (V95%) was 99.4 (range, 96.3-99.9). DVH analysis of parotid gland showed a median value of the mean parotid dose of 32.1 Gy (range, 17.5-70.3 Gy). The median parotid volume receiving a dose <26 Gy was 51.2%. Quality of life evaluation demonstrated an initial deterioration of almost all scales and items in QLQ-C30 and QLQ-H and N35. Most items improved in time, and some reached baseline values 18 months after treatment. Conclusion: DVH analysis, scintigraphic evaluation of parotid function, and quality of life assessment of our patient group showed that helical tomotherapy makes it possible to preserve parotid gland function without compromising disease control. We recommend mean parotid doses of <34 Gy and doses <26 Gy to a maximum 47% of the parotid

  19. Wegener's granulomatosis: parotid involvement and associated pancreatitis with C.T. findings.

    PubMed

    Stuckey, S L; Smart, P J

    1992-11-01

    Parotid enlargement is an uncommon physical sign and even less commonly the reason for referral for computerised tomography (CT) as the aetiology is usually self-evident. In cases referred for CT examination Wegener's granulomatosis should be considered, particularly if the pathology appears bilateral. This diagnosis may be confirmed by biopsy and/or supported by Anti-Neutrophil Cytoplasmic Antibody (ANCA) assay. A case of Wegener's granulomatosis with parotid gland involvement and temporally related pancreatitis with pseudocyst formation is reported. This is the second reported case of possible pancreatic involvement in Wegeners granulomatosis and approximately the tenth reported case of salivary gland involvement.

  20. Influence of altered CSF solute composition on parotid salivary secretion in goats.

    PubMed

    Olsson, K

    1976-06-01

    Infusions of hypertonic NaCl solution into the CSF of the lateral cerebral ventricle of the goat caused a marked reduction in parotid salivary flow concomitant with a rise in salivary [Na+]. Corresponding infusions of iso- or hypertonic glucose and glycerol solutions affected salivary secretion in the opposite direction. The possibility is discussed that a periventricular sodium-sensitive mechanism, which is of importance in the central control of fluid balance, also may participate in the regulation of parotid secretion in the goat. This interpretation of the results is to some extent obscured by the observation of a high incidence of intermittent rumination during the intraventricular infusions of glucose and glycerol solution.

  1. A fibrous histiocytoma of intermediate malignancy arisen from the parotid gland.

    PubMed

    Khalkhali, Kazem; Azizi, Mohammad-Reza; Atighechi, Saeid

    2007-01-01

    The light microscopic and immunohistochemical characteristics of a case of fibrous histiocytoma of intermediate malignancy arising from the parotid gland are presented. This neoplasm is rare in this site and must be distinguished from other spindle cell tumors of the parotid gland, particularly those of epithelial and myoepithelial origins. Histologic characteristics similar to those displayed by dermatofibroma and dermatofibrosarcoma protuberans help to differentiate this tumor from other spindle cell tumors. The absence of cytochemical epithelial markers is useful for establishing the diagnosis. This tumor appears to have arisen from mesenchymal elements within the gland.

  2. Respiratory flow phenomena and gravitational deposition in a three-dimensional space-filling model of the pulmonary acinar tree.

    PubMed

    Sznitman, Josué; Heimsch, Thomas; Wildhaber, Johannes H; Tsuda, Akira; Rösgen, Thomas

    2009-03-01

    The inhalation of micron-sized aerosols into the lung's acinar region may be recognized as a possible health risk or a therapeutic tool. In an effort to develop a deeper understanding of the mechanisms responsible for acinar deposition, we have numerically simulated the transport of nondiffusing fine inhaled particles (1 mum and 3 microm in diameter) in two acinar models of varying complexity: (i) a simple alveolated duct and (ii) a space-filling asymmetrical acinar branching tree following the description of lung structure by Fung (1988, "A Model of the Lung Structure and Its Validation," J. Appl. Physiol., 64, pp. 2132-2141). Detailed particle trajectories and deposition efficiencies, as well as acinar flow structures, were investigated under different orientations of gravity, for tidal breathing motion in an average human adult. Trajectories and deposition efficiencies inside the alveolated duct are strongly related to gravity orientation. While the motion of larger particles (3 microm) is relatively insensitive to convective flows compared with the role of gravitational sedimentation, finer 1 microm aerosols may exhibit, in contrast, complex kinematics influenced by the coupling between (i) flow reversal due to oscillatory breathing, (ii) local alveolar flow structure, and (iii) streamline crossing due to gravity. These combined mechanisms may lead to twisting and undulating trajectories in the alveolus over multiple breathing cycles. The extension of our study to a space-filling acinar tree was well suited to investigate the influence of bulk kinematic interaction on aerosol transport between ductal and alveolar flows. We found the existence of intricate trajectories of fine 1 microm aerosols spanning over the entire acinar airway network, which cannot be captured by simple alveolar models. In contrast, heavier 3 microm aerosols yield trajectories characteristic of gravitational sedimentation, analogous to those observed in the simple alveolated duct. For both

  3. Effect of glucagon on digestive enzyme synthesis, transport and secretion in mouse pancreatic acinar cells.

    PubMed Central

    Singh, M

    1980-01-01

    1. Effect of glucagon on amylase secretion and lactic dehydrogenase (LDH) release from functionally intact dissociated pancreatic acinar cells and acini was studied. 2. In dissociated rat pancreatic acinar cells, the rate of amylase secretion was increased by 70% with bethanechol (maximally effective concentration, 10(-4) M) and 125% with A23187 (10(-5) M), but the response to cholecystokinin-pancreozymin (CCK-PZ) was inconsistent. In dissociated cells from mouse pancreas, the increases amounted to 78% with bethanechol (10(-4) M), 134% with A23187 (10(-5) M) and 82% with CCK-PZ (maximally effective concentration, 0 . 01 u. ml.-1). Glucagon in concentrations ranging from 10(-7) to 10(-4) M increased amylase secretion by 3, 26, 67 and 80%, whereas secretin (10(-8)--10(-5) M) increased amylase secretion by 8, 39, 88 and 138%. LDH release was increased with A23187 in concentrations greater than 10(-6) M. 3. CCK-PZ, bethanechol and A23187 used in maximal concentrations potentiated the effect of a submaximal dose of glucagon whereas secretin did not have an additive or a potentiating effect. 4. Pancreatic acini were approximately 3 times more responsive to secretagogues than cells. The dose--response curves to bethanechol, glucagon and CCK-PZ for increase in amylase secretion were similar. LDH release was not increased by these agents. Cytochalasin B (5 microgram ml.-1) which is known to disrupt the integrity of luminal membrane inhibited the amylase secretion stimulated by glucagon, bethanechol and CCK-PZ. 5. Glucagon inhibited incorporation of a mixture of fifteen 14C-labelled amino acids (algal profile, Schwarz Mann) into perchloric acid precipitable proteins in dissociated mouse pancreatic acini within 30 min. 6. In 'pulse-chase' experiments, glucagon decreased the specific activity of zymogen granules isolated by differential centrifugation, from pancreatic lobules (120 min) and increased the specific activity of radiolabelled proteins in the medium (60 and 120 min

  4. Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca2+ oscillations in mouse pancreatic acinar cells

    PubMed Central

    Huang, Zebing; Wang, Haiyan; Wang, Jingke; Zhao, Mengqin; Sun, Nana; Sun, Fangfang; Shen, Jianxin; Zhang, Haiying; Xia, Kunkun; Chen, Dejie; Gao, Ming; Hammer, Ronald P.; Liu, Qingrong; Xi, Zhengxiong; Fan, Xuegong; Wu, Jie

    2016-01-01

    Emerging evidence demonstrates that the blockade of intracellular Ca2+ signals may protect pancreatic acinar cells against Ca2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB2Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca2+ oscillations and L-arginine-induced enhancement of Ca2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis. PMID:27432473

  5. Encapsulation of primary salivary gland cells in enzymatically degradable poly(ethylene glycol) hydrogels promotes acinar cell characteristics.

    PubMed

    Shubin, Andrew D; Felong, Timothy J; Schutrum, Brittany E; Joe, Debria S L; Ovitt, Catherine E; Benoit, Danielle S W

    2017-03-01

    Radiation therapy for head and neck cancers leads to permanent xerostomia due to the loss of secretory acinar cells in the salivary glands. Regenerative treatments utilizing primary submandibular gland (SMG) cells show modest improvements in salivary secretory function, but there is limited evidence of salivary gland regeneration. We have recently shown that poly(ethylene glycol) (PEG) hydrogels can support the survival and proliferation of SMG cells as multicellular spheres in vitro. To further develop this approach for cell-based salivary gland regeneration, we have investigated how different modes of PEG hydrogel degradation affect the proliferation, cell-specific gene expression, and epithelial morphology within encapsulated salivary gland spheres. Comparison of non-degradable, hydrolytically-degradable, matrix metalloproteinase (MMP)-degradable, and mixed mode-degradable hydrogels showed that hydrogel degradation by any mechanism is required for significant proliferation of encapsulated cells. The expression of acinar phenotypic markers Aqp5 and Nkcc1 was increased in hydrogels that are MMP-degradable compared with other hydrogel compositions. However, expression of secretory acinar proteins Mist1 and Pip was not maintained to the same extent as phenotypic markers, suggesting changes in cell function upon encapsulation. Nevertheless, MMP- and mixed mode-degradability promoted organization of polarized cell types forming tight junctions and expression of the basement membrane proteins laminin and collagen IV within encapsulated SMG spheres. This work demonstrates that cellularly remodeled hydrogels can promote proliferation and gland-like organization by encapsulated salivary gland cells as well as maintenance of acinar cell characteristics required for regenerative approaches. Investigation is required to identify approaches to further enhance acinar secretory properties.

  6. Determination of parotid urea secretion in sheep by means of ultrasonic flow probes and a multifactorial regression analysis.

    PubMed

    Cirio, A; Méot, F; Delignette-Muller, M L; Boivin, R

    2000-02-01

    For determination of the dynamics of parotid urea secretion in conscious sheep, a previously standardized transit time ultrasonic flow metering system was used to measure bilateral parotid flow. Six ewes fed for ad libitum consumption were prepared under halothane anesthesia with ultrasonic probes around both parotid ducts; these ducts were also cannulated orally. After probe encapsulation (8 d), parotid flows were recorded during 24 h, and samples of saliva and blood for urea determination were obtained hourly. Jaw movements were recorded by means of a submandibular balloon to monitor feeding behavior. Urea concentration in parotid saliva was 60 to 74% of that in plasma (a positive linear correlation existed) and was poorly influenced by the parotid flow. The amount of urea secreted with parotid saliva was directly related to the salivation rate. To calculate the urea secretion in parotid saliva, a multiple linear regression model was developed from computer-calculated parotid flows over 1-min periods and plasma urea concentration. The model was accurate because the plot of calculated vs measured values was not significantly different from the line of identity. The daily parotid urea N varied from .35 to 1.02 g among ewes. The higher urea secretion rate found during rumination and eating (1.32+/-.42 and .98 +/-.33 mg/min, respectively) vs. during rest (.60+/-.39 mg/ min, P<.05) was due to higher salivation rates (5.17 +/-1.46, 3.56+/-.90, and 2.04+/-.52 mL/min, respectively, P<.05) rather than to changes in saliva urea concentrations (saliva:plasma urea ratio = .65+/-.04, .67+/-.04, and .68+/-.03, respectively). Of the daily parotid urea output, 40.8% was secreted during rest. The contribution of parotid urea N to the ruminal N pool was relatively small (1.2 to 3.7% of the N intake, which was 23.0 to 33.6 g/d). These techniques allowed direct and precise measurements of parotid urea secretion without disturbing the animal or altering the physiological regulation

  7. Polyethylenimine-mediated expression of transgenes in the acinar cells of rats salivary glands in vivo

    PubMed Central

    Sramkova, Monika; Parente, Laura; Wigand, Timothy; Aye, Myo-Pale'; Shitara, Akiko; Weigert, Roberto

    2015-01-01

    Non viral-mediated transfection of plasmid DNA provides a fast and reliable way to express various transgenes in selected cell populations in live animals. Here, we show an improvement of a previously published method that is based on injecting plasmid DNA into the ductal system of the salivary glands in live rats. Specifically, using complexes between plasmid DNA and polyethyleneimine (PEI) we show that the expression of the transgenes is directed selectively to the salivary acinar cells. PEI does not affect the ability of cells to undergo regulated exocytosis, which was one of the main drawbacks of the previous methods. Moreover PEI does not affect the proper localization and targeting of transfected proteins, as shown for the apical plasma membrane water channel aquaporin 5 (AQP5). Overall, this approach, coupled with the use of intravital microscopy, permits to conduct localization and functional studies under physiological conditions, in a rapid, reliable, and affordable fashion. PMID:25621283

  8. Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms.

    PubMed

    Srinivasan, Padmanabhan; Kapadia, Rubina; Biswas, Arundhati; Said, Hamid M

    2014-11-01

    Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5'-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na(+) dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms.

  9. FK506 induces biphasic Ca2+ release from microsomal vesicles of rat pancreatic acinar cells.

    PubMed

    Ozawa, Terutaka

    2006-07-01

    The effect of the immunosuppressant drug FK506 on microsomal Ca2+ release was investigated in rat pancreatic acinar cells. When FK506 (0.1-200 microM) was added to the microsomal vesicles at a steady state of ATP-dependent 45Ca2+ uptake, FK506 caused a dose-dependent and a biphasic release of 45Ca2+. Almost 10% of total 45Ca2+ uptake was released at FK506 concentrations up to 10 microM (Km=0.47 microM), and 60% of total 45Ca2+ uptake was released at FK506 concentrations over 10 microM (Km=55 microM). Preincubation of the vesicles with cyclic ADP-ribose (cADPR, 0.5 microM) increased the FK506 (< or =10 microM)-induced 45Ca2+ release (Ozawa T, Biochim Biophys Acta 1693: 159-166, 2004). Preincubation with heparin (200 microg/ml) resulted in significant inhibition of the FK506 (30 microM)-induced 45Ca2+ release. Subsequent addition of inositol 1,4,5-trisphosphate (IP3, 5 microM) after FK506 (100 microM)-induced 45Ca2+ release did not cause any release of 45Ca2+. These results indicate that two types of FK506-induced Ca2+ release mechanism operate in the endoplasmic reticulum of rat pancreatic acinar cells: a high-affinity mechanism of Ca2+ release, which involves activation of the ryanodine receptor, and a low-affinity mechanism of Ca2+ release, which involves activation of the IP3 receptor.

  10. The Acinar Cage: Basement Membranes Determine Molecule Exchange and Mechanical Stability of Human Breast Cell Acini

    PubMed Central

    Gaiko-Shcherbak, Aljona; Fabris, Gloria; Dreissen, Georg; Merkel, Rudolf; Hoffmann, Bernd; Noetzel, Erik

    2015-01-01

    The biophysical properties of the basement membrane that surrounds human breast glands are poorly understood, but are thought to be decisive for normal organ function and malignancy. Here, we characterize the breast gland basement membrane with a focus on molecule permeation and mechanical stability, both crucial for organ function. We used well-established and nature-mimicking MCF10A acini as 3D cell model for human breast glands, with ether low- or highly-developed basement membrane scaffolds. Semi-quantitative dextran tracer (3 to 40 kDa) experiments allowed us to investigate the basement membrane scaffold as a molecule diffusion barrier in human breast acini in vitro. We demonstrated that molecule permeation correlated positively with macromolecule size and intriguingly also with basement membrane development state, revealing a pore size of at least 9 nm. Notably, an intact collagen IV mesh proved to be essential for this permeation function. Furthermore, we performed ultra-sensitive atomic force microscopy to quantify the response of native breast acini and of decellularized basement membrane shells against mechanical indentation. We found a clear correlation between increasing acinar force resistance and basement membrane formation stage. Most important native acini with highly-developed basement membranes as well as cell-free basement membrane shells could both withstand physiologically relevant loads (≤ 20 nN) without loss of structural integrity. In contrast, low-developed basement membranes were significantly softer and more fragile. In conclusion, our study emphasizes the key role of the basement membrane as conductor of acinar molecule influx and mechanical stability of human breast glands, which are fundamental for normal organ function. PMID:26674091

  11. The Acinar Cage: Basement Membranes Determine Molecule Exchange and Mechanical Stability of Human Breast Cell Acini.

    PubMed

    Gaiko-Shcherbak, Aljona; Fabris, Gloria; Dreissen, Georg; Merkel, Rudolf; Hoffmann, Bernd; Noetzel, Erik

    2015-01-01

    The biophysical properties of the basement membrane that surrounds human breast glands are poorly understood, but are thought to be decisive for normal organ function and malignancy. Here, we characterize the breast gland basement membrane with a focus on molecule permeation and mechanical stability, both crucial for organ function. We used well-established and nature-mimicking MCF10A acini as 3D cell model for human breast glands, with ether low- or highly-developed basement membrane scaffolds. Semi-quantitative dextran tracer (3 to 40 kDa) experiments allowed us to investigate the basement membrane scaffold as a molecule diffusion barrier in human breast acini in vitro. We demonstrated that molecule permeation correlated positively with macromolecule size and intriguingly also with basement membrane development state, revealing a pore size of at least 9 nm. Notably, an intact collagen IV mesh proved to be essential for this permeation function. Furthermore, we performed ultra-sensitive atomic force microscopy to quantify the response of native breast acini and of decellularized basement membrane shells against mechanical indentation. We found a clear correlation between increasing acinar force resistance and basement membrane formation stage. Most important native acini with highly-developed basement membranes as well as cell-free basement membrane shells could both withstand physiologically relevant loads (≤ 20 nN) without loss of structural integrity. In contrast, low-developed basement membranes were significantly softer and more fragile. In conclusion, our study emphasizes the key role of the basement membrane as conductor of acinar molecule influx and mechanical stability of human breast glands, which are fundamental for normal organ function.

  12. Rhein Induces a Necrosis-Apoptosis Switch in Pancreatic Acinar Cells

    PubMed Central

    Zhao, Xianlin; Li, Juan; Zhu, Shifeng; Liu, Yiling; Zhao, Jianlei; Wan, Meihua; Tang, Wenfu

    2014-01-01

    Objectives. The Chinese herbal medicine Da-Cheng-Qi decoction can regulate a necrosis-apoptosis switch in injured pancreatic acinar cells. This study investigated the effects of rhein, a component of this medicine, on a necrosis-apoptosis switch in pancreatic rat AR42J cells. Methods. Cerulein-treated AR42J cells were used. After pretreatment with 479, 119.8, or 29.9 μg/L rhein, cells were cocultured with rhein and cerulein (10−8 M) for 4, 8, or 16 h. Apoptosis and necrosis were examined using annexin V and propidium iodide costaining. Mitochondria-dependent apoptosis-associated proteins were examined using enzyme-linked immunosorbent assays and western blotting. Results. Few cells died in untreated samples. The number was significantly higher in 16-h-cerulein-treated samples and treatment with 479 μg/L rhein most effectively increased the apoptotic-to-necrotic cell ratio (P < 0.05). In cerulein-treated cells, rhein increased the concentrations of p53, cytochrome C, and caspase-3, and increased the Bax/Bcl-2 ratio in a time- and dose-dependent manner, with the maximum effect in cells treated with 479 μg/L rhein for 16 h (P < 0.05). Conclusions. Rhein induces the necrosis-apoptosis switch in injured pancreatic acinar cells in a time- and dose-dependent manner. Mitochondria-dependent apoptosis signaling pathways might play an important role in this effect. PMID:24959186

  13. Ethanol exerts dual effects on calcium homeostasis in CCK-8-stimulated mouse pancreatic acinar cells

    PubMed Central

    Fernández-Sánchez, Marcela; del Castillo-Vaquero, Angel; Salido, Ginés M; González, Antonio

    2009-01-01

    Background A significant percentage of patients with pancreatitis often presents a history of excessive alcohol consumption. Nevertheless, the patho-physiological effect of ethanol on pancreatitis remains poorly understood. In the present study, we have investigated the early effects of acute ethanol exposure on CCK-8-evoked Ca2+ signals in mouse pancreatic acinar cells. Changes in [Ca2+]i and ROS production were analyzed employing fluorescence techniques after loading cells with fura-2 or CM-H2DCFDA, respectively. Results Ethanol, in the concentration range from 1 to 50 mM, evoked an oscillatory pattern in [Ca2+]i. In addition, ethanol evoked reactive oxygen species generation (ROS) production. Stimulation of cells with 1 nM or 20 pM CCK-8, respectively led to a transient change and oscillations in [Ca2+]i. In the presence of ethanol a transformation of 20 pM CCK-8-evoked physiological oscillations into a single transient increase in [Ca2+]i in the majority of cells was observed. Whereas, in response to 1 nM CCK-8, the total Ca2+ mobilization was significantly increased by ethanol pre-treatment. Preincubation of cells with 1 mM 4-MP, an inhibitor of alcohol dehydrogenase, or 10 μM of the antioxidant cinnamtannin B-1, reverted the effect of ethanol on total Ca2+ mobilization evoked by 1 nM CCK-8. Cinnamtannin B-1 blocked ethanol-evoked ROS production. Conclusion ethanol may lead, either directly or through ROS generation, to an over stimulation of pancreatic acinar cells in response to CCK-8, resulting in a higher Ca2+ mobilization compared to normal conditions. The actions of ethanol on CCK-8-stimulation of cells create a situation potentially leading to Ca2+ overload, which is a common pathological precursor that mediates pancreatitis. PMID:19878551

  14. Altered coupling of muscarinic acetylcholine receptors in pancreatic acinar carcinoma of rat

    SciTech Connect

    Chien, J.L.; Warren, J.R.

    1986-03-05

    The structure and function of muscarinic acetylcholine receptors (mAChR) in acinar carcinoma cells have been compared to mAChR in normal pancreatic acinar cells. Similar 80 kD proteins identified by SDS-PAGE of tumor and normal mAChR affinity-labeled with the muscarinic antagonist /sup 3/H-propylbenzilyl-choline mustards, and identical binding of the antagonist N-methylscopolamine to tumor and normal cells (K/sub D/approx.4x10/sup -10/ M), indicate conservation of mAChR proteins in carcinoma cells. Carcinoma mAChR display homogeneous binding of the agonists carbamylcholine (CCh), K/sub D/approx.3x10/sup -5/ M, and oxotremorine (Oxo), K/sub D/approx.x10/sup -6/ M, whereas normal cells display heterogeneous binding, with a minor component of high affinity interactions for CCh, K/sub D/approx.3x10/sup -6/ M, and Oxo, K/sub D/approx.2x/sup -17/ M, and a major component of low affinity interactions for CCh, K/sub D/approx.1x10/sup -4/ M, and Oxo, K/sub D/approx.2x10/sup -5/ M. Both carcinoma and normal cells exhibit concentration-dependent CCh-stimulated increase in cytosolic free Ca/sup 2 +/, as measured by intracellular Quin 2 fluorescence and /sup 45/Ca/sup 2 +/ efflux. However, carcinoma cells demonstrate 50% maximal stimulation of intracellular Ca/sup 2 +/ release at a CCh concentration (EC/sub 50/approx.6x10/sup -7/ M) one log below that observed for normal cells. The authors propose an altered coupling of mAChR to intracellular Ca/sup 2 +/ homeostasis in carcinoma cells, which is manifest as a single activated receptor state for agonist binding, and increased sensitivity to muscarinic receptor stimulation of Ca/sup 2 +/ release.

  15. Interaction of bombesin and litorin with specific membrane receptors on pancreatic acinar cells

    PubMed Central

    Jensen, R. T.; Moody, T.; Pert, C.; Rivier, J. E.; Gardner, J. D.

    1978-01-01

    We have prepared 125I-labeled [Tyr4]bombesin and have examined the kinetics, stoichiometry, and chemical specificity with which the labeled peptide binds to dispersed acini from guinea pig pancreas. Binding of 125I-labeled [Tyr4]-bombesin was saturable, temperature-dependent, and reversible and reflected interaction of the labeled peptide with a single class of binding sites on the plasma membrane of pancreatic acinar cells. Each acinar cell possessed approximately 5000 binding sites, and binding of the tracer to these sites could be inhibited by [Tyr4]bombesin [concentration for half-maximal effect (Kd), 2 nM], bombesin (Kd, 4 nM), or litorin (Kd, 40 nM) but not by eledoisin, physalemin, somatostatin, carbachol, atropine, secretin, vasocative intestinal peptide, neurotensin, or bovine pancreatic polypeptide. At high concentrations (>0.1 μM), cholecystokinin and caerulein each caused a small (15-20%) reduction in binding of lableled [Tyr4]bombesin. With bombesin, litorin, and [Tyr4]bombesin, there was a close correlation between the relative potency for inhibition of binding of labeled [Tyr4]bombesin and that for stimulation of amylase secretion. For a given peptide, however, a 10-fold higher concentration was required for half-maximal inhibition of binding than for half-maximal stimulation of amylase secretion, calcium outflux, or cyclic GMP accumulation. These results indicate that dispersed acini from guinea pig pancreas possess a single class of receptors that interact with [Tyr4]bombesin, bombesin, and litorin and that occupation of 25% of these receptors will cause a maximal biological response. PMID:216015

  16. Radioprotective effects of pyrroloquinoline quinone on parotid glands in C57BL/6J mice

    PubMed Central

    Huang, Yuanqing; Chen, Ning; Miao, Dengshun

    2016-01-01

    The aim of the present study was to investigate whether pyrroloquinoline quinine (PQQ) serve a radioprotective role in parotid gland damage induced by total body irradiation (TBI) in C57BL/6J mice. A total of 15 female 8-week-old C57BL/6J mice were randomly assigned into three treatment groups: i) Untreated control (no irradiation); ii) 4 gray (Gy) X-ray irradiation; iii) 4 Gy X-ray irradiation with additional dietary PQQ (4 mg PQQ/kg in normal diet). Each group included five mice. After 4 weeks, all animals were collected for evaluating the phenotype, body weight, pathological and biochemical parameters. The results indicated that PQQ had biological effects on total body phenotype. PQQ could partially rescue TBI-induced damage to parotid glands. In addition, PQQ served radioprotective effects on parotid glands via multiple mechanisms, such as promoting proliferation, inhibiting apoptosis and senescence, upregulating antioxidant ability, scavenging reactive oxygen species and reducing DNA damage. The results of the present study demonstrate that PQQ serves a radioprotective role in parotid gland damage induced by TBI, possibly via inhibiting oxidative stress and participating in DNA damage repair. The study provides experimental and theoretical knowledge for the development of radioprotective clinical drugs. PMID:28105098

  17. The suitability of common metrics for assessing parotid and larynx autosegmentation accuracy.

    PubMed

    Beasley, William J; McWilliam, Alan; Aitkenhead, Adam; Mackay, Ranald I; Rowbottom, Carl G

    2016-03-08

    Contouring structures in the head and neck is time-consuming, and automatic seg-mentation is an important part of an adaptive radiotherapy workflow. Geometric accuracy of automatic segmentation algorithms has been widely reported, but there is no consensus as to which metrics provide clinically meaningful results. This study investigated whether geometric accuracy (as quantified by several commonly used metrics) was associated with dosimetric differences for the parotid and larynx, comparing automatically generated contours against manually drawn ground truth contours. This enabled the suitability of different commonly used metrics to be assessed for measuring automatic segmentation accuracy of the parotid and larynx. Parotid and larynx structures for 10 head and neck patients were outlined by five clinicians to create ground truth structures. An automatic segmentation algorithm was used to create automatically generated normal structures, which were then used to create volumetric-modulated arc therapy plans. The mean doses to the automatically generated structures were compared with those of the corresponding ground truth structures, and the relative difference in mean dose was calculated for each structure. It was found that this difference did not correlate with the geometric accuracy provided by several metrics, notably the Dice similarity coefficient, which is a commonly used measure of spatial overlap. Surface-based metrics provided stronger correlation and are, therefore, more suitable for assessing automatic seg-mentation of the parotid and larynx.

  18. Effects of methotrexate on rat parotid and submandibular glands and their secretions

    SciTech Connect

    McBride, R.K.

    1986-01-01

    Experimental animals were injected intraperitoneally with methotrexate for 3 days. Parotid and submandibular main ducts were cannulated and saliva flow was evoked by either intravenous infusion of acetylcholine or an intravenous injection of benthanechol. Methotrexate was found to reduce significantly mean food consumption, body weight, and parotid gland wet weights. Experimental animal salivary total gland DNA levels were not different, but total parotid gland RNA, protein, amylase and water content, and submandibular gland RNA were significantly lower compared to control. Acetylcholine, but not bethanechol, evoked parotid protein and amylase outputs and submandibular protein output from experimental animals were significantly higher than the control groups'. The increased outputs were apparently linked to ..beta..-adrenergic receptor activation, since hexamethonium or propranolol eliminated the significant increases while phenoxybenzamine did not. Plasma catecholamine levels were significantly higher in the methotrexate treated animals and probably played a role in the salivary gland ..beta..-adrenergic activation. Methotrexate treatment significantly increased the submandibular gland ..beta..-adrenergic receptor concentration as determined by (/sup 3/H)-dihydroalprenolol receptor binding assays. Muscarinic receptor concentrations determined with (/sup 3/H)-quinuclidninyl benzilate were not changed.

  19. Comparison of Complications in Parotid Surgery With Harmonic Scalpel Versus Cold Instruments.

    PubMed

    Yang, Xiaoyong; Yu, Yang; Li, Dapeng; Dong, Li

    2017-02-22

    Complications following parotid surgery with harmonic scalpel versus cold instruments were seldom discussed. The authors retrospectively analyzed the medical record of 94 patients who received parotid surgery at Tianjin National Clinical Research Center for Cancer between January 2012 and October 2015, and compared the complications in patients operated with either Harmonic FCS9 (HF) or traditional cold instruments (CI). The mean operative time was 65.1 minutes in HF group versus 88.9 minutes for CI group. Intraoperative blood loss was 35 mL in HF group versus 55 mL in CI group. The mean drainage time was 3.7 days in HF group compared with 4.9 days in CI group. The mean total drainage volume was 62 mL in HF group versus 89 mL in CI group. The occurrence of Frey syndrome showed no difference in these 2 groups. Thus, the use of the HF in the surgical treatment of parotid disease is safe and confers advantages over conventional methods of parotid dissection.

  20. Comparative pharmacokinetics of sulfamethazine in plasma and parotid saliva of sheep.

    PubMed

    Pulido, E; Meot, F; Sumano, H; Boivin, R

    1998-04-01

    Salivary output in sheep is large enough to be considered a physiologic body fluid compartment. The hypothesis for this work was that pharmacokinetics of sulfamethazine in saliva was similar to that in plasma. A reliable technique was developed to measure parotid salivary output. Mean output of saliva was 3.18 +/- 1.04 L from a single parotid gland per day with a mean flow of 2.21 +/- 0.43 mL/min. Using concentrations of sulfamethazine in parotid saliva made it possible to calculate the total passage of sulfamethazine to parotid saliva, which was calculated to be 3.5% of the total dose. Pharmacokinetic variables obtained for sulfamethazine in plasma and in saliva were closely related (AUC 1408 micrograms.h/mL and AUC 1484 micrograms.h/mL; Vdarea 0.434 L/kg and Vdarea 0.374 L/kg; t 1/2 beta 4.30 h and 3.46 h, respectively) and no substantial differences were observed. The convenience of using salivary concentrations of sulfamethazine for drug monitoring is discussed.

  1. Parotid Gland Function After Radiotherapy: The Combined Michigan and Utrecht Experience

    SciTech Connect

    Dijkema, Tim; Raaijmakers, Cornelis P.J.; Ten Haken, Randall K.; Roesink, Judith M.; Braam, Petra M.; Houweling, Anette C.; Moerland, Marinus A.; Eisbruch, Avraham; Terhaard, Chris H.J.

    2010-10-01

    Purpose: To analyze the combined and updated results from the University of Michigan and University Medical Center Utrecht on normal tissue complication probability (NTCP) of the parotid gland 1 year after radiotherapy (RT) for head-and-neck (HN) cancer. Patients and Methods: A total of 222 prospectively analyzed patients with various HN malignancies were treated with conventional and intensity-modulated RT. Stimulated individual parotid gland flow rates were measured before RT and 1 year after RT using Lashley cups at both centers. A flow ratio <25% of pretreatment was defined as a complication. The data were fitted to the Lyman-Kutcher-Burman model. Results: A total of 384 parotid glands (Michigan: 157; Utrecht: 227 glands) was available for analysis 1 year after RT. Combined NTCP analysis based on mean dose resulted in a TD{sub 50} (uniform dose leading to 50% complication probability) of 39.9 Gy and m (steepness of the curve) of 0.40. The resulting NTCP curve had good qualitative agreement with the combined clinical data. Mean doses of 25-30 Gy were associated with 17-26% NTCP. Conclusions: A definite NTCP curve for parotid gland function 1 year after RT is presented, based on mean dose. No threshold dose was observed, and TD{sub 50} was equal to 40 Gy.

  2. Possible involvement of parotid beta-adrenergic receptors in the etiology of sialadenosis.

    PubMed

    Chilla, R; Witzemann, V; Opaitz, M; Arglebe, C

    1981-01-01

    The concentration of beta-adrenergic receptors was determined in rat and human parotid glands, in normal tissue as well as after sympathetic denervation of the rat, and in human sialadenosis. Receptor levels were clearly elevated after denervation of the rat and in sialadenosis. The possible implications of these findings for the etiology of human sialadenosis are discussed.

  3. Skull Base Involvement by Acinic Cell Carcinoma of the Parotid Gland

    PubMed Central

    Breen, Joseph T.; Carlson, Matthew L.; Link, Michael J.; Moore, Eric J.; Neff, Brian A.; Driscoll, Colin L.W.

    2012-01-01

    Objective Describe the clinical course and outcomes of patients with primary acinic cell carcinoma (ACC) of the parotid gland with skull base invasion or metastasis. Design Retrospective case series (1995–2011) at a single institution. Results Ten patients met study criteria. Mean and median time from initial diagnosis of parotid ACC to development of skull base disease were 14.6 and 10.2 years, respectively. Two patients demonstrated skull base disease on initial presentation. Those who pursued further treatment after developing disease at the skull base underwent surgery (4/7), stereotactic radiosurgery (4/7), or external beam radiation (3/7). The 10-year Kaplan-Meier estimated overall survival after initial diagnosis of parotid ACC was 80%. Once skull base invasion occurred, 2-year estimated overall survival was 50%. Conclusion Although primary ACC of the parotid generally caries an excellent prognosis, tumor control with cranial base disease is difficult and the majority of patients present with late aggressive recurrences. Our observations underscore the importance of long-term follow-up in this patient group. PMID:24294553

  4. Facial Paralysis Secondary to Extensive Perineural Spread of Adenocarcinoma of the Parotid Gland Identified by PET/CT.

    PubMed

    Achong, Dwight M; Zloty, Martin

    2016-06-01

    Brain MRI in an 82-year-old man with presumed Bell's palsy revealed a clinically unsuspected right parotid gland mass but no other acute findings. Biopsy revealed poorly differentiated adenocarcinoma. Staging F-FDG PET/CT revealed an FDG-avid parotid mass, abnormal FDG uptake along the course of the facial nerve from mass to skull base, and multiple FDG-avid right level II neck lymph nodes and hepatic metastases. The PET/CT findings and prolonged clinical course suggest that diffuse perineural spread of tumor from a smoldering parotid neoplasm, and not idiopathic Bell's palsy, was responsible for the patient's facial paralysis.

  5. Polymer coated liposomes for dental drug delivery--interactions with parotid saliva and dental enamel.

    PubMed

    Nguyen, S; Hiorth, M; Rykke, M; Smistad, G

    2013-09-27

    The interactions between pectin coated liposomes and parotid saliva and dental enamel were studied to investigate their potential to mimic the protective biofilm formed naturally on tooth surfaces. Different pectin coated liposomes with respect to pectin type (LM-, HM- and AM-pectin) and concentration (0.05% and 0.2%) were prepared. Interactions between the pectin coated liposomes and parotid saliva were studied by turbidimetry and imaging by atomic force microscopy. The liposomes were adsorbed to hydroxyapatite (HA) and human dental enamel using phosphate buffer and parotid saliva as adsorption media. A continuous flow was imposed on the enamel surfaces for various time intervals to examine their retention on the dental enamel. The results were compared to uncoated, charged liposomes. No aggregation tendencies for the pectin coated liposomes and parotid saliva were revealed. This makes them promising as drug delivery systems to be used in the oral cavity. In phosphate buffer the adsorption to HA of pectin coated liposomes was significantly lower than the negative liposomes. The difference diminished in parotid saliva. Positive liposomes adsorbed better to the dental enamel than the pectin coated liposomes. However, when subjected to flow for 1h, no significant differences in the retention levels on the enamel were found between the formulations. For all formulations, more than 40% of the liposomes still remained on the enamel surfaces. At time point 20 min the retention of HM-pectin coated and positive liposomes were significantly higher. It was concluded that pectin coated liposomes can adsorb to HA as well as to the dental enamel. Their ability to retain on the enamel surfaces promotes the concept of using them as protective structures for the teeth.

  6. The Cutaneous Rabbit Revisited

    ERIC Educational Resources Information Center

    Flach, Rudiger; Haggard, Patrick

    2006-01-01

    In the cutaneous rabbit effect (CRE), a tactile event (so-called attractee tap) is mislocalized toward an adjacent attractor tap. The effect depends on the time interval between the taps. The authors delivered sequences of taps to the forearm and asked participants to report the location of one of the taps. The authors replicated the original CRE…

  7. Autoantibody Production in Rabbits

    PubMed Central

    Asherson, G. L.; Dumonde, D. C.

    1963-01-01

    The sera of rabbits injected with rat liver, kidney, heart, muscle, spleen and brain in Freund's complete adjuvant fixed complement with rabbit tissue. This complement-fixing activity was attributed to autoantibodies which were able to fix complement in vitro with the tissue of the rabbit in which they occurred. Absorption, gel diffusion and antibody and antigen titrations indicated that some of the anti-liver, anti-kidney, anti-heart, anti-muscle and anti-brain sera contained organ-specific autoantibody. The sera also contained autoantibody reacting with widely distributed antigen(s), which was relatively labile at 65°. The anti-kidney and anti-brain sera reacted with distinct antigens which were extracted from rabbit kidney and brain with a mixture of chloroform and methanol. The natural autoantibody of Kidd and Friedewald was usually labile at 65° and behaved like a macroglobulin on sucrose gradient centrifugation. Sera taken 1 week after immunization with rat tissue contained heat-labile macroglobulin antibody. However, sera taken 1 month after immunization also contained small molecular weight antibody which was stable at 65°. PMID:13965166

  8. The role of alpha 6 beta 1 integrin and EGF in normal and malignant acinar morphogenesis of human prostatic epithelial cells.

    PubMed

    Bello-DeOcampo, D; Kleinman, H K; Webber, M M

    2001-09-01

    Complex multiple interactions between cells and extracellular matrix occur during acinar morphogenesis involving integrin receptors and growth factors. Changes in these interactions occur during carcinogenesis as cells progress from a normal to a malignant, invasive phenotype. We have developed human prostatic epithelial cell lines of the same lineage, which represent multiple steps in carcinogenesis, similar to prostatic intraepithelial neoplasia and subsequent tumor progression. The non-tumorigenic, RWPE-1 and the tumorigenic WPE1-NB27 and WPE1-NB26 cell lines were used to examine their ability to undergo acinar morphogenesis in a 3-D cell culture model and its relationship to invasion, integrin expression and EGF presence. An inverse relationship between the degree of acinar formation and invasive ability was observed. The non-tumorigenic, non-invasive RWPE-1 and the low tumorigenic, low invasive, WPE1-NB27 cells show high and decreased acinar forming ability, respectively, while the more invasive WPE1-NB26 cells show a loss of acinar formation. While RWPE-1 acini show basal expression of alpha 6 beta 1 integrin, which correlates with their ability to polarize and form acini, WPE1-NB27 cells lack alpha 6 but show basal, but weaker expression of beta 1 integrin. WPE1-NB26 cells show loss alpha 6 and abnormal, diffused beta 1 integrin expression. A dose-dependent decrease in acinar formation was observed in RWPE-1 cells when cell proliferation was induced by EGF. Anti-functional antibody to EGF caused an increase in acinar formation in RWPE-1 cells. These results suggest that malignant cells lose the ability to undergo acinar morphogenesis and that the degree of this loss appears to be related to invasive ability, EGF levels and alterations in laminin-specific integrin expression. This model system mimics different steps in prostate carcinogenesis and has applications in the secondary and tertiary prevention of prostate cancer.

  9. Autoantibody production in rabbits

    PubMed Central

    Asherson, G. L.; Holborow, E. J.

    1966-01-01

    Rabbits received two injections of dead bacteria in Freund's complete adjuvant. One month later the sera of the rabbits were examined for autoantibodies against gut by indirect immunofluorescence using the rabbit's own stomach, ileum and colon taken at post mortem. Autoantibodies against colon were found in three out of seven rabbits injected with one particular strain of Escherichia coli O64 and in a few animals injected with other E. coli, Salmonella arizona, Proteus mirabilis, Klebsiella pneumoniae and Streptococcus faecalis. The antigen, with which the autoantibodies reacted, behaved like mucus and was detected in the colon and sometimes in the ileum and the stomach. Three patterns of staining were observed: (a) staining of the superficial mucosa of the colon with sparing of the deep glands; (b) staining of scattered groups of glands in the deepest part of the colon with sparing of the superficial glands (this pattern of staining was associated with staining of the superficial mucosa of the body of the stomach); and (c) staining of both the superficial and deep glands of the colon. None of the sera tested reacted with the bronchial or salivary glands. Polysaccharide preparations of the colon, but not the stomach, inhibited the reaction of the autoantibodies with colon in the sera tested. The amount of antigen needed to inhibit the basal staining was much greater than that needed to inhibit the superficial staining. It was concluded that rabbits may produce autoantibodies to colon and in some cases to ileum and stomach following the injection of certain dead bacteria in Freund's complete adjuvant. ImagesFIGS. 1-2FIG. 3FIG. 4FIG. 5FIG. 6 PMID:4956607

  10. Predictors of Pathologic Outcome of Focal FDG Uptake in the Parotid Gland Identified on Whole Body FDG PET Imaging

    PubMed Central

    Mabray, Marc C.; Behr, Spencer C.; Naeger, David M.; Flavell, Robert R.; Glastonbury, Christine M.

    2015-01-01

    Purpose To test whether patient's primary malignancy type and presence of FDG-avid cervical lymph node(s) are predictors of pathologic outcome of incidental focal FDG-avid parotid lesions. Basic Procedures Retrospective cohort study of pathologically proven incidental cases. Main Findings Focal parotid FDG uptake in the setting of head and neck cancer/melanoma(OR=24.6,p<0.01), lymphoma(OR=7.2,p=0.02), or FDG-avid cervical lymph node(s)(OR=3.6,p=0.07) has a higher odds of representing metastases. No malignant primary parotid tumors were incidentally discovered. Principal Conclusions In patients with head and neck cancer/melanoma, lymphoma, or FDG-avid cervical lymph node(s) there was a higher odds that focal parotid FDG uptake was a metastasis. PMID:26324219

  11. TNF-α inhibits aquaporin 5 expression in human salivary gland acinar cells via suppression of histone H4 acetylation.

    PubMed

    Yamamura, Yoshiko; Motegi, Katsumi; Kani, Kouichi; Takano, Hideyuki; Momota, Yukihiro; Aota, Keiko; Yamanoi, Tomoko; Azuma, Masayuki

    2012-08-01

    Sjögren's syndrome is a systemic autoimmune disease characterized by reductions in salivary and lacrimal secretions. The mechanisms underlying these reductions remain unclear. We have previously shown that TNF-α plays an important role in the destruction of acinar structures. Here we examined TNF-α's function in the expression of aquaporin (AQP) 5 in human salivary gland acinar cells. Immortalized human salivary gland acinar (NS-SV-AC) cells were treated with TNF-α, and then the expression levels of AQP5 mRNA and protein were analysed. In addition, the mechanisms underlying the reduction of AQP5 expression by TNF-α treatment were investigated. TNF-α-treatment of NS-SV-AC cells significantly suppressed the expression levels of AQP5 mRNA and protein, and reduced the net fluid secretion rate. We examined the expression and activation levels of DNA methyltransferases (Dnmts) in NS-SV-AC cells treated with TNF-α. However, no significant changes were observed in the expression or activation levels of Dnmt1, Dnmt3a or Dnmt3b. Although we also investigated the role of NF-κB activity in the TNF-α-induced suppression of AQP5 expression in NS-SV-AC cells, we detected similar TNF-α suppression of AQP5 expression in non-transfected cells and in a super-repressor form of IκBα cDNA-transfected cell clones. However, interestingly, chromatin immunoprecipitation analysis demonstrated a remarkable decrease in levels of acetylated histone H4 associated with the AQP5 gene promoter after treatment with TNF-α in NS-SV-AC cells. Therefore, our results may indicate that TNF-α inhibition of AQP5 expression in human salivary gland acinar cells is due to the epigenetic mechanism by suppression of acetylation of histone H4.

  12. Label retaining cells (LRCs) with myoepithelial characteristic from the proximal acinar region define stem cells in the sweat gland.

    PubMed

    Leung, Yvonne; Kandyba, Eve; Chen, Yi-Bu; Ruffins, Seth; Kobielak, Krzysztof

    2013-01-01

    Slow cycling is a common feature shared among several stem cells (SCs) identified in adult tissues including hair follicle and cornea. Recently, existence of unipotent SCs in basal and lumenal layers of sweat gland (SG) has been described and label retaining cells (LRCs) have also been localized in SGs; however, whether these LRCs possess SCs characteristic has not been investigated further. Here, we used a H2BGFP LRCs system for in vivo detection of infrequently dividing cells. This system allowed us to specifically localize and isolate SCs with label-retention and myoepithelial characteristics restricted to the SG proximal acinar region. Using an alternative genetic approach, we demonstrated that SG LRCs expressed keratin 15 (K15) in the acinar region and lineage tracing determined that K15 labeled cells contributed long term to the SG structure but not to epidermal homeostasis. Surprisingly, wound healing experiments did not activate proximal acinar SG cells to participate in epidermal healing. Instead, predominantly non-LRCs in the SG duct actively divided, whereas the majority of SG LRCs remained quiescent. However, when we further challenged the system under more favorable isolated wound healing conditions, we were able to trigger normally quiescent acinar LRCs to trans-differentiate into the epidermis and adopt its long term fate. In addition, dissociated SG cells were able to regenerate SGs and, surprisingly, hair follicles demonstrating their in vivo plasticity. By determining the gene expression profile of isolated SG LRCs and non-LRCs in vivo, we identified several Bone Morphogenetic Protein (BMP) pathway genes to be up-regulated and confirmed a functional requirement for BMP receptor 1A (BMPR1A)-mediated signaling in SG formation. Our data highlight the existence of SG stem cells (SGSCs) and their primary importance in SG homeostasis. It also emphasizes SGSCs as an alternative source of cells in wound healing and their plasticity for regenerating

  13. Metabotropic glutamate receptor 1 disrupts mammary acinar architecture and initiates malignant transformation of mammary epithelial cells

    PubMed Central

    Teh, Jessica L. F.; Shah, Raj; La Cava, Stephanie; Dolfi, Sonia C.; Mehta, Madhura S.; Kongara, Sameera; Price, Sandy; Ganesan, Shridar; Reuhl, Kenneth R.; Hirshfield, Kim M.

    2016-01-01

    Metabotropic glutamate receptor 1 (mGluR1/Grm1) is a member of the G-protein-coupled receptor superfamily, which was once thought to only participate in synaptic transmission and neuronal excitability, but has more recently been implicated in non-neuronal tissue functions. We previously described the oncogenic properties of Grm1 in cultured melanocytes in vitro and in spontaneous melanoma development with 100 % penetrance in vivo. Aberrant mGluR1 expression was detected in 60–80 % of human melanoma cell lines and biopsy samples. As most human cancers are of epithelial origin, we utilized immortalized mouse mammary epithelial cells (iMMECs) as a model system to study the transformative properties of Grm1. We introduced Grm1 into iMMECs and isolated several stable mGluR1-expressing clones. Phenotypic alterations in mammary acinar architecture were assessed using three-dimensional morphogenesis assays. We found that mGluR1-expressing iMMECs exhibited delayed lumen formation in association with decreased central acinar cell death, disrupted cell polarity, and a dramatic increase in the activation of the mitogen-activated protein kinase pathway. Orthotopic implantation of mGluR1-expressing iMMEC clones into mammary fat pads of immunodeficient nude mice resulted in mammary tumor formation in vivo. Persistent mGluR1 expression was required for the maintenance of the tumorigenic phenotypes in vitro and in vivo, as demonstrated by an inducible Grm1-silencing RNA system. Furthermore, mGluR1 was found be expressed in human breast cancer cell lines and breast tumor biopsies. Elevated levels of extracellular glutamate were observed in mGluR1-expressing breast cancer cell lines and concurrent treatment of MCF7 xenografts with glutamate release inhibitor, riluzole, and an AKT inhibitor led to suppression of tumor progression. Our results are likely relevant to human breast cancer, highlighting a putative role of mGluR1 in the pathophysiology of breast cancer and the potential

  14. Bilateral painful parotid lumps and a lump in the groin: An uncommon presentation of common Kikuchi's disease

    PubMed Central

    Mirgh, Sumeet Prakash; Satiya, Jinendra; Sorabjee, Jehangir Soli

    2016-01-01

    Kikuchi-Fujimoto disease (KFD) is an under-recognized disease most commonly presenting with cervical lymphadenopathy, fever, and cytopenias in young females. Bilateral parotid enlargement is usually caused by infections (e.g., mumps) and autoimmune conditions (e.g., Sjogren syndrome). Parotid enlargement, inguinal lymphadenopathy, and pyrexia of unknown origin are uncommon presenting features of KFD and should be suspected in the appropriate setting. PMID:27843864

  15. Apoptotic Mechanisms of Peroxisome Proliferator–Activated Receptor-γ Activation in Acinar Cells During Acute Pancreatitis

    PubMed Central

    Xu, Ping; Lou, Xiao-Li; Chen, Cheng

    2016-01-01

    Objective The objective of this study was to determine the mechanism by which activation of peroxisome proliferator–activated receptor-γ promotes apoptosis of acinar cells in pancreatitis. Methods AR42j cells pretreated with the peroxisome proliferator–activated receptor-γ agonist pioglitazone were activated by cerulein as an in vitro model of acute pancreatitis. Inflammatory cytokines and amylase were detected by enzyme-linked immunosorbent assay. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis was measured by flow cytometry and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling staining. Activity of caspases was determined. Bax and Bcl-2 levels were assayed by Western blot. Results Cytokines, amylase, and cellular proliferation decreased in pioglitazone-pretreated cells. Pioglitazone increased the activity of caspases 3, 8, and 9 in cerulein-activated AR42j cells as well as in the pancreas of rats 3 hours after induction of severe acute pancreatitis. Acinar cell apoptosis was induced by reducing the mitochondrial membrane potential in the pioglitazone group. Pioglitazone increased expression of proapoptotic Bax proteins and decreased antiapoptotic Bcl-2 in cerulein-induced AR42j cells and decreased Bcl-2 levels in pancreatic tissue of severe acute pancreatitis rats 1 and 3 hours after induction. Conclusion Pioglitazone may promote apoptosis of acinar cells through both intrinsic and extrinsic apoptotic pathways in acute pancreatitis. PMID:26495791

  16. Relationship between parotid amylase secretion and osmolality in the gastric contents of rats fed a pelleted or liquid diet.

    PubMed

    Kurahashi, M; Inomata, K

    1999-12-01

    The relationship between parotid amylase secretion and the osmolality in the gastric contents of rats fed a pelleted or liquid diet was investigated. In sham-operated rats fed a pelleted diet, amylase activity in the parotid glands decreased, amylase activity in the plasma increased, and there was strong amylase activity in the gastric contents. As a result, both reducing sugar concentration and osmolality in the gastric contents increased. In parotid duct-ligated rats, the feeding of a pelleted diet affected neither parotid nor plasma amylase activity and there was little amylase activity in the gastric contents; this resulted in decreased starch digestion. The amylase activity in the gastric contents of rats fed a liquid diet was lower than that of rats fed the pelleted diet. Both the reducing sugar concentration and osmolality in the gastric contents of rats fed the liquid diet were lower than those of rats fed the pelleted diet. However, both the reducing sugar concentration and osmolality in the gastric contents of rats fed the liquid diet were higher than those in the liquid diet itself. A small quantity of parotid amylase seems to effectively digest a large part of the starch in the stomaches of rats fed the liquid diet. These findings suggest that amylase secreted from parotid glands increases osmolality in the gastric contents via the production of reducing sugars from starch in rats when fed either pelleted or liquid diets.

  17. The accuracy of fine-needle aspiration cytology for diagnosis of parotid gland masses: a clinicopathological study of 114 patients

    PubMed Central

    GUDMUNDSSON, Jens Kristjan; AJAN, Aida; ABTAHI, Jahan

    2016-01-01

    ABSTRACT Objective Fine-needle aspiration cytology is a valuable method for preoperative assessment of head and neck tumors. However, its accuracy in detection of salivary gland masses is controversial compared with other methods. The aim of this work was to evaluate the effectiveness and accuracy of fine-needle aspiration cytology (FNAC) in the diagnosis of parotid gland masses. Material and Methods Over a 10-year period, 126 parotid gland masses were resected. Retrospective chart reviews of 114 patients were performed. The results of FNAC and final histological diagnosis were compared and the accuracy of FNAC was determined. Results Final histological evaluation revealed 11 malignant tumors and 103 benign lesions. Pleomorphic adenoma was the most common neoplasm (63%), followed by Warthin’s tumor (17.5%). The sensitivity of FNAC in detecting malignant tumors was 73% and the specificity was 97%. Positive predictive value (PPV) was 73% and negative predictive value (NPV) was 97%. The overall accuracy of FNAC in detecting parotid masses was 95%. False-negative diagnosis was found in mucoepidermoid carcinoma, acinic cell carcinoma, and epithelial-myoepithelial carcinoma whereas there was false-positive diagnosis in cases of pleomorphic adenoma and normal parotid gland tissue. Conclusion FNAC is a reliable minimally invasive diagnostic method with a high sensitivity in diagnosis of lesions in parotid glands. The sensitivity of detection of malignant tumors in parotid glands was low due to the biopsy technique used, and depended on tumor location. Postoperative complications decreased after superficial parotidectomy. PMID:28076460

  18. From rabbit antibody repertoires to rabbit monoclonal antibodies

    PubMed Central

    Weber, Justus; Peng, Haiyong; Rader, Christoph

    2017-01-01

    In this review, we explain why and how rabbit monoclonal antibodies have become outstanding reagents for laboratory research and increasingly for diagnostic and therapeutic applications. Starting with the unique ontogeny of rabbit B cells that affords highly distinctive antibody repertoires rich in in vivo pruned binders of high diversity, affinity and specificity, we describe the generation of rabbit monoclonal antibodies by hybridoma technology, phage display and alternative methods, along with an account of successful humanization strategies. PMID:28336958

  19. Rabbits killing birds revisited.

    PubMed

    Zhang, Jimin; Fan, Meng; Kuang, Yang

    2006-09-01

    We formulate and study a three-species population model consisting of an endemic prey (bird), an alien prey (rabbit) and an alien predator (cat). Our model overcomes several model construction problems in existing models. Moreover, our model generates richer, more reasonable and realistic dynamics. We explore the possible control strategies to save or restore the bird by controlling or eliminating the rabbit or the cat when the bird is endangered. We confirm the existence of the hyperpredation phenomenon, which is a big potential threat to most endemic prey. Specifically, we show that, in an endemic prey-alien prey-alien predator system, eradication of introduced predators such as the cat alone is not always the best solution to protect endemic insular prey since predator control may fail to protect the indigenous prey when the control of the introduced prey is not carried out simultaneously.

  20. Aerosol bolus dispersion in acinar airways--influence of gravity and airway asymmetry.

    PubMed

    Ma, Baoshun; Darquenne, Chantal

    2012-08-01

    The aerosol bolus technique can be used to estimate the degree of convective mixing in the lung; however, contributions of different lung compartments to measured dispersion cannot be differentiated unambiguously. To estimate dispersion in the distal lung, we studied the effect of gravity and airway asymmetry on the dispersion of 1 μm-diameter particle boluses in three-dimensional computational models of the lung periphery, ranging from a single alveolar sac to four-generation (g4) structures of bifurcating airways that deformed homogeneously during breathing. Boluses were introduced at the beginning of a 2-s inhalation, immediately followed by a 3-s exhalation. Dispersion was estimated by the half-width of the exhaled bolus. Dispersion was significantly affected by the spatial orientation of the models in normal gravity and was less in zero gravity than in normal gravity. Dispersion was strongly correlated with model volume in both normal and zero gravity. Predicted pulmonary dispersion based on a symmetric g4 acinar model was 391 ml and 238 ml under normal and zero gravity, respectively. These results accounted for a significant amount of dispersion measured experimentally. In zero gravity, predicted dispersion in a highly asymmetric model accounted for ∼20% of that obtained in a symmetric model with comparable volume and number of alveolated branches, whereas normal gravity dispersions were comparable in both models. These results suggest that gravitational sedimentation and not geometrical asymmetry is the dominant factor in aerosol dispersion in the lung periphery.

  1. Pancreatic panniculitis associated with acinar cell carcinoma of the pancreas: a case report.

    PubMed

    Zheng, Zhen Jiang; Gong, Jun; Xiang, Guang Ming; Mai, Gang; Liu, Xu Bao

    2011-05-01

    Pancreatic panniculitis is a rare type of disorder associated with pancreatic diseases. We describe here a case of 54-year-old man who was admitted to the Department of Dermatology with the diagnosis of erythema nodosum. The patient presented with a 9-month history of painful erythematous nodules on the extremities, joint pain and swelling, and weight loss. A highly elevated level of pancreatic lipase was found on the laboratory examinations. The biopsy specimens from the skin lesions showed subcutaneous fat necrosis. Abdominal computed tomography (CT) revealed a large mass with central necrosis in the body and tail of the pancreas. Distal pancreatectomy, splenectomy and partial transverse colectomy were successfully performed on day 17 of the hospitalization. The histopathologic findings supported the diagnosis of acinar cell carcinoma of the pancreas (ACCP). Postoperatively, the level of serum lipase returned to normal, and the skin lesions and joint manifestations gradually regressed. However, the swelling did not significantly resolve in the left knee. In view of the non-specific clinical presentation of this disease, clinicians should be alert and have a high index of suspicion for pancreatic panniculitis.

  2. Pancreatic ducts as an important route of tumor extension for acinar cell carcinoma of the pancreas.

    PubMed

    Ban, Daisuke; Shimada, Kazuaki; Sekine, Shigeki; Sakamoto, Yoshihiro; Kosuge, Tomoo; Kanai, Yae; Hiraoka, Nobuyoshi

    2010-07-01

    Acinar cell carcinoma (ACC) of the pancreas is very rare, which usually grows expansively. Recently, a variant of ACC with predominant growth in the pancreatic ducts has been proposed, and is speculated to have potentially less aggressive behavior. The aim of this study was to investigate how the pancreatic duct system is related to the growth and extension of ACC. We reviewed the detailed gross and histologic features of 13 cases of ACC, of which 7 (54%) showed intraductal polypoid growth (IPG) of the tumor in the large pancreatic ducts with a mean IPG length of 24.8 mm. Tumors with IPG were found to spread characteristically along the pancreatic ducts as extending polypoid projections, filling the ducts and destroying the duct walls, although tumors did not tend to extend beyond the pancreatic parenchyma. Comparison of the clinicopathologic characteristics showed that ACC with IPG had less infiltrative features including lymphatic, venous, and neural invasion, formation of tumor thrombus in the portal vein, nodal metastasis, and invasion beyond the pancreas to the surrounding organs; death in only 1 case (14%) of ACC with IPG was the result of ACC itself. In contrast, ACC without IPG frequently showed more infiltrative growth, and was the cause of death in 50% of patients with this type of tumor. Intraductal dissemination of ACC in pancreatic ducts was proven in 1 case of ACC with IPG. These findings suggest that a significant proportion of ACC shows IPG, which is potentially linked to less aggressive clinicopathologic characteristics.

  3. Mixed acinar-neuroendocrine-ductal carcinoma of the pancreas: a tale of three lineages.

    PubMed

    Anderson, Mark J; Kwong, Christina A; Atieh, Mohammed; Pappas, Sam G

    2016-06-02

    Most pancreatic cancers arise from a single cell type, although mixed pancreatic carcinomas represent a rare exception. The rarity of these aggressive malignancies and the limitations of fine-needle aspiration (FNA) pose significant barriers to diagnosis and appropriate management. We report a case of a 54-year-old man presenting with abdominal pain, jaundice and a hypodense lesion within the uncinate process on CT. FNA suggested poorly differentiated adenocarcinoma, which was subsequently resected via pancreaticoduodenectomy. Pathological analysis yielded diagnosis of invasive mixed acinar-neuroendocrine-ductal pancreatic carcinoma. Given the rare and deadly nature of these tumours, clinicians must be aware of their pathophysiology and do practice with a high degree of clinical suspicion, when appropriate. Surgical resection and thorough pathological analysis with immunohistochemical staining and electron microscopy remain the standards of care for mixed pancreatic tumours without gross evidence of metastasis. Diligent characterisation of the presentation and histological findings associated with these neoplasms should continue in order to promote optimal diagnostic and therapeutic strategies.

  4. [Protein malnutrition and response of pancreatic acinar cells to stimulation by cholecystokinin].

    PubMed

    Prost, J; Belleville, J

    1988-01-01

    Pancreatic lobules were isolated from 2 groups of male Wistar rats after 23 days of diet. A control group (C) fed on a 20% protein diet (16% gluten + 4% casein) and an experimental group (E) on a 5% protein diet (4% gluten + 1% casein). After isolation, lobules were preincubated 10 min with 10 muCi [3H]-leucine, washed, then incubate within Krebs Ringer bicarbonate Hepes. Basal secretion, then stimulated secretion (50 pM of cholecystokinin (CCK] of radioactive and non-radioactive protein and amylase outputs were measured. During basal secretion, in (E) group, lobules secreted more proteins than (C) one, the same outputs of amylase and radioactive protein were observed in both groups. The stimulated secretion by CCK increased the outputs of non-radioactive protein and amylase of lobules (T) (2-3 fold), but was without effect on lobule (E) outputs. Therefore, a low-protein diet involved a decrease of CCK sensibility on acinar cells, this fact might be mediated by a decreasing number and/or affinity of their CCK receptors.

  5. A quantitative assessment of volumetric and anatomic changes of the parotid gland during intensity-modulated radiotherapy for head and neck cancer using serial computed tomography

    SciTech Connect

    Ajani, Abdallah A.; Qureshi, Muhammad M.; Kovalchuk, Nataliya; Orlina, Lawrence; Sakai, Osamu; Truong, Minh Tam

    2013-10-01

    To evaluate the change in volume and movement of the parotid gland measured by serial contrast-enhanced computed tomography scans in patients with head and neck cancer treated with parotid-sparing intensity-modulated radiotherapy (IMRT). A prospective study was performed on 13 patients with head and neck cancer undergoing dose-painted IMRT to 69.96 Gy in 33 fractions. Serial computed tomography scans were performed at baseline, weeks 2, 4, and 6 of radiotherapy (RT), and at 6 weeks post-RT. The parotid volume was contoured at each scan, and the movement of the medial and lateral borders was measured. The patient's body weight was recorded at each corresponding week during RT. Regression analyses were performed to ascertain the rate of change during treatment as a percent change per fraction in parotid volume and distance relative to baseline. The mean parotid volume decreased by 37.3% from baseline to week 6 of RT. The overall rate of change in parotid volume during RT was−1.30% per fraction (−1.67% and−0.91% per fraction in≥31 Gy and<31 Gy mean planned parotid dose groups, respectively, p = 0.0004). The movement of parotid borders was greater in the≥31 Gy mean parotid dose group compared with the<31 Gy group (0.22% per fraction and 0.14% per fraction for the lateral border and 0.19% per fraction and 0.06% per fraction for the medial border, respectively). The median change in body weight was−7.4% (range, 0.75% to−17.5%) during RT. A positive correlation was noted between change in body weight and parotid volume during the course of RT (Spearman correlation coefficient, r = 0.66, p<0.01). Head and neck IMRT results in a volume loss of the parotid gland, which is related to the planned parotid dose, and the patient's weight loss during RT.

  6. [Possible relation between viruses and oromaxillofacial tumors. V. Demonstration of hemagglutination-inhibiting anti-BK virus antibodies in patients with tumors of the parotid gland].

    PubMed

    Stoian, M; Zaharia, O; Suru, M; Constantinescu, E; Goldstein, I; Nastac, E

    1987-01-01

    Anti-BK-virus hemagglutination inhibiting antibodies were revealed in 81.8% of the patients with parotid gland tumors. Results of the investigations conducted on oromaxillofacial tumors including the parotid gland ones are discussed from the point of view of the presence of viral antigens (herpes-, SV40 and BK-viruses) and of specific antibodies. Possible implication of the papova viruses in the etiopathogenesis of the parotid gland tumors in humans are also discussed.

  7. Rabbit renotropic system

    SciTech Connect

    Areas, J.; Yun, G.C.; Rahmat, J.; Gersten, D.; Goel, R.; Preuss, H.G.

    1988-04-01

    Elevated levels of a specific renal growth factor, renotropin, have been associated with spontaneous hypertension. To examine this association more closely, we have undertaken the development of a better assay system to characterize and purify renotropin. Sera from rabbits prior to operation (control) and at a specified time after unilateral nephrectomy (uni) were examined for renotropic activity. Comparing the effects of uni to control sera in the same rabbit, significant stimulation of 3H-thymidine incorporation into the DNA of primary rabbit kidney cultures incubated in D-valine medium to eliminate fibroblast growth was noted: at 3 days postoperatively 73% (n = 13), at 7 days 103% (n = 39), at 10 days 130% (n = 31), at 21 days 101% (n = 24), at 42 days 89% (n = 13). All values were at least P less than 0.01. The stimulatory properties were dose-dependent but reached a plateau at high serum concentrations. Comparing CPM/mg protein in uni/control in different concentrations of sera 7 days postoperatively, uni versus control were 67/44 at 5% v/v, 139/72 at 10% v/v, 261/161 at 20% v/v, and 243/136 at 40% v/v. The renotropic effect of uni sera remained after dialysis in incubation medium and after sera were heated in boiling water for 5 minutes. Renal extracts obtained from growing kidneys 7 days postnephrectomy augmented renotropic activity. Atrial natriuretic factor, ouabain, PGF2 alpha, PGE1, and cAMP did not possess renotropic activity. We conclude that the primary rabbit kidney culture assay for renotropin is highly sensitive and will be an important tool to comprehend the role of renotropin in the pathogenesis of hypertension.

  8. Basal cell adenoma of the parotid gland. Case report and review of the literature.

    PubMed

    González-García, Raúl; Nam-Cha, Syong H; Muñoz-Guerra, Mario F; Gamallo-Amat, C

    2006-03-01

    Basal cell adenoma of the salivary glands is an uncommon type of monomorphous adenoma. Its most frequent location is the parotid gland. It usually appears as a firm and mobile slow-growing mass. Histologically, isomorphic cells in nests and interlaced trabecules with a prominent basal membrane are observed. It is also characterized by the presence of a slack and hyaline stroma and the absence of myxoid or condroid stroma. In contrast to pleomorphic adenoma, it tends to be multiple and its recurrence rate after surgical excision is high. Due to prognostic implications, differential diagnosis with basal cell adenocarcinoma, adenoid cystic carcinoma and basaloid squamous cell carcinoma is mandatory. We describe a case of basal cell adenoma of the parotid gland. We also review the literature and discuss the diagnosis and management of this rare entity.

  9. Relapsed Acinic Cell Carcinoma of the Parotid Gland With Diffuse Distant Metastasis

    PubMed Central

    Khelfa, Yousef; Mansour, Munthir; Abdel-Aziz, Yousef; Raufi, Ali; Denning, Krista; Lebowicz, Yehuda

    2016-01-01

    Acinic cell carcinoma (ACC) is an uncommon salivary gland neoplasm that generally displays an indolent growth pattern. Most cases arise in the major glands, particularly the parotid. However, it can arise from minor salivary glands in the oral cavity and aero-digestive tract. Although ACC is generally a low-grade malignant tumor, poorly differentiated and high-grade transformed variants exhibit a propensity for late recurrence and metastasis. There are no adequate clinical trials that define the optimal approach to patients with metastatic salivary gland tumors due to its rarity. Systemic therapy is reserved for cases where local therapy, such as radiation or metastasectomy, is not appropriate. Nevertheless, there is insufficient data in the literature regarding the chemotherapy of choice for metastatic ACC. In this article, we report a case of metastatic ACC of the right parotid gland that progressed on carboplatin and paclitaxel after partial response followed by doxorubicin and is currently on checkpoint inhibitor treatment. PMID:27847831

  10. Predicting facial nerve invasion by parotid gland carcinoma and outcome of facial reanimation.

    PubMed

    Preis, M; Soudry, E; Bachar, G; Shufel, H; Feinmesser, R; Shpitzer, T

    2010-01-01

    We sought to define risk factors for facial nerve involvement in parotid gland carcinoma and assess the outcome of facial nerve reanimation. Medical records were reviewed of 66 patients who underwent surgery for parotid carcinoma in 2000–2007 at a tertiary hospital. Patient and tumor characteristics were compared between patients with and without facial nerve involvement and were analyzed on their influence on functional outcome following reanimation. Facial nerve involvement was verified intraoperatively in 24 patients, of whom 16 underwent reanimation during ablative surgery. Deep lobe invasion was significantly associated with intraoperative finding of facial nerve involvement. Tumors larger than 4 cm and salivary duct carcinoma had an obvious trend for facial nerve involvement. House-Brackmann score at 12 months was 3-4 in most patients. Deep lobe involvement and large tumor size may identify patients at risk of facial nerve involvement. Reanimation is associated with good functional outcome regardless of patient's age.

  11. Multi-atlas-based Segmentation of the Parotid Glands of MR Images in Patients Following Head-and-neck Cancer Radiotherapy

    PubMed Central

    Cheng, Guanghui; Yang, Xiaofeng; Wu, Ning; Xu, Zhijian; Zhao, Hongfu; Wang, Yuefeng; Liu, Tian

    2015-01-01

    Xerostomia (dry mouth), resulting from radiation damage to the parotid glands, is one of the most common and distressing side effects of head-and-neck cancer radiotherapy. Recent MRI studies have demonstrated that the volume reduction of parotid glands is an important indicator for radiation damage and xerostomia. In the clinic, parotid-volume evaluation is exclusively based on physicians’ manual contours. However, manual contouring is time-consuming and prone to inter-observer and intra-observer variability. Here, we report a fully automated multi-atlas-based registration method for parotid-gland delineation in 3D head-and-neck MR images. The multi-atlas segmentation utilizes a hybrid deformable image registration to map the target subject to multiple patients’ images, applies the transformation to the corresponding segmented parotid glands, and subsequently uses the multiple patient-specific pairs (head-and-neck MR image and transformed parotid-gland mask) to train support vector machine (SVM) to reach consensus to segment the parotid gland of the target subject. This segmentation algorithm was tested with head-and-neck MRIs of 5 patients following radiotherapy for the nasopharyngeal cancer. The average parotid-gland volume overlapped 85% between the automatic segmentations and the physicians’ manual contours. In conclusion, we have demonstrated the feasibility of an automatic multi-atlas based segmentation algorithm to segment parotid glands in head-and-neck MR images. PMID:25914491

  12. Traumatic diseases of parotid gland and sequalae. Review of literature and case reports.

    PubMed

    Akinbami, B O

    2009-06-01

    Parotid gland injuries are accompanied by a large number of sequelae. The aim of this paper is to highlight the importance of thorough management of these parotid glandinjuries especially at initial presentation in order to minimize the complications that accompany these injuries. A review of the aetiology and management of the existing cases of parotid gland injuries obtained from published journals and internet search as well as a report of two cases managed in our centre is presented in this paper. A total of about 70 cases in the previous literatures were reviewed of which assault was responsible for almost 90% of the cases. Sialoceles and fistulae were the main sequelae of these injuries. More than half of the cases (54%) were managed by conservative methods. Surgical drainage was done in about 44% cases; where the Stenson's ducts were accessible, primary repair was done. Excision of the gland was done in very few cases. The two cases managed in our centre were due to assault from broken bottles and road traffic accident respectively and both were managed by conservative methods. The first patient was a case of sialocele following the injury, which resolved within 3 weeks after the cyst formation with reduction in food intake, aspirations and external surgical drainage; while the second patient was a case of persistent fistula which healed after about 5 weeks following the trauma. Follow-up of both patients for about 3 months revealed no further leakage or accumulation of saliva. Management of these injuries involves a thorough understanding of the structure and function of the parotid gland and closely related tissues.

  13. [Immunoglobulin and electrolyte levels in sialadenosis of the parotid (author's transl)].

    PubMed

    Proescher, H J

    1975-03-01

    A comparison of 15 patients with sialadenosis of the parotid gland and 15 control patients was made of their levels of immunoglobulins A, G and M, sodium, potassium, calcium, chloride, albumin, inorganic phosphate, cholesterin, uric acid and creatinin. Those patients with sialadenosis, in comparison with the control group and the findings in other reports, show reduced immunoglobulin A and increased potassium in the parotic secretion. The disturbance of function of the acinic cell is discussed.

  14. Association between microtubules and Golgi vesicles isolated from rat parotid glands.

    PubMed

    Coffe, G; Raymond, M N

    1990-01-01

    We report an isolation procedure of trans-Golgi vesicles (GVs) from rat parotid glands. Various organelle markers were used, particularly galactosyl transferase as a trans-Golgi marker, to test the purity of the GV fraction. A quantitative in vitro binding assay between microtubules and GVs is described. The vesicles were incubated with taxol-induced microtubules, layered between 50% and 43% sucrose cushions and subjected to centrifugation. Unlike free microtubules which were sedimented, the GV-bound microtubules co-migrated upward with GVs. Quantification of these bound microtubules was carried out by densitometric scanning of Coomassie blue-stained gels. The association between microtubules and GVs followed a saturation curve, with a plateau value of 20 micrograms of microtubule protein bound to 500 micrograms of GV fraction. The half-saturation of the GV sites was obtained with a microtubule concentration of 20 micrograms/ml. Electron microscopy of negatively stained re-floated material showed numerous microtubule-vesicle complexes. Coating of microtubules with an excess of brain microtubule-associated proteins (MAPs) abolished binding. In the absence of exogenous microtubules, we showed that the GV fraction was already interacting with a class of endogenous rat parotid microtubules. This class of colcemid and cold-stable microtubules represents 10-20% of the total tubulin content of the parotid cell.

  15. Acinic Cell Carcinoma of the Parotid Gland with Four Morphological Features

    PubMed Central

    Rosero, David S; Alvarez, Ramiro; Gambó, Paula; Alastuey, María; Valero, Alberto; Torrecilla, Nerea; Roche, A. Belén; Simón, Sara

    2016-01-01

    Acinic cell carcinoma arising in salivary glands is a rare tumor, accounting for 2% to 5% of the primary neoplasms of the parotid gland. When these tumors are well-differentiated, the neoplasia has innocuous aspect, due to the similarity to normal parotid tissue. This makes the diagnosis difficult. Initially the malignancy of this tumor was uncertain; however, recent studies have declared it as malignant. The female / male ratio is 3:2. The nodule usually presents as solitary and well defined shape. Several authors have used different terms to describe histomorphological patterns of these tumors. Four descriptive categories (solid, microcystic, papillary-cystic and follicular) are useful for pathologists. Here we report a case of a 49 yr old man with a left parotid nodule of 5 cm. Parotidectomy was performed at the Hospital Universitario Miguel Servet, in Zaragoza (Spain). The microscopy showed a tumor with acinic semblance, having the four morphologic patterns previously described. The morphological and immunohistochemical study was consistent with the diagnosis of acinic cell carcinoma. PMID:27499783

  16. Large cell neuroendocrine carcinoma of the parotid gland: case report and literature review.

    PubMed

    Casas, Pablo; Bernáldez, Ricardo; Patrón, Mercedes; López-Ferrer, Pilar; García-Cabezas, Miguel A

    2005-03-01

    A 74-year-old male presented with a large polinodular mass in the neck. Fine needle aspiration cytology (FNAC) showed an undifferentiated large cell carcinoma. Computed tomography (CT) showed a large parotid mass with multiple satelite nodules. The remaining radiological studies were normal. Radical parotidectomy was performed. The tumor was a large cell carcinoma with neuroendocrine features and positive immunostain for neuroendocrine markers. The patient received postoperative radiotherapy and was free of tumor eight months later. Only four cases of large cell neuroendocrine carcinoma (LCNEC) of the salivary gland have been communicated. All of them have involved the parotid gland. This tumor presents in elderly patients as a large infiltrating parotid mass. Fine needle aspiration cytology serves to recognize the carcinoma, but it fails in recognizing the neuroendocrine features of the tumor. The histopathological features of this tumor are the same as in other organs. Chromogranin and synaptophysin are useful immunohistochemical markers. A primary location of the tumor in another organ, specially the lung, should be ruled out. Surgery is the main treatment modality and can be complemented with postoperative radiotherapy. The prognosis seems to be poor. More studies are needed to better define the therapeutical alternatives and prognostic factors of these rare tumors.

  17. Local Rhomboid Flap Reconstruction for Skin Defects After Excising Large Parotid Gland Tumors.

    PubMed

    Hung, Min-Hui; Liao, Chun-Ta; Kang, Chung-Jan; Huang, Shiang-Fu

    2017-01-01

    Most parotid tumors grow slowly, and sometimes these patients do not request surgical treatment until the tumors become large and affect their appearance. The surgical treatment of these large tumors is usually accompanied by large skin defects after excision, and it is challenging for surgeons to close the defect primarily. This report describes the case of a 68-year-old man with a left parotid gland tumor (largest dimension, 110 mm) and the case of a 79-year-old man with a left parotid gland tumor measuring approximately 77 mm that had existed for decades. These patients underwent facial nerve dissection and parotidectomy with skin sacrifice. The large skin defects after the parotidectomy were successfully reconstructed with local rhomboid flaps. No facial palsy, wound disruption, flap edge loss, or major complications occurred after the surgeries. Except for the scars, the color of the cheek flap was not apparent from the periphery. In conclusion, local rhomboid flap reconstruction is a rapid and practical technique for reconstructing medium to large skin defects in the cheek and upper neck regions after tumor excisions. The flap was reliable in blood supply and cosmetic outcome.

  18. Both IgA subclasses are reduced in parotid saliva from patients with AIDS.

    PubMed Central

    Müller, F; Frøland, S S; Hvatum, M; Radl, J; Brandtzaeg, P

    1991-01-01

    Secretory IgA (SIgA), the isotypes IgA1 and IgA2, and IgM were measured by ELISA in stimulated parotid saliva from patients with AIDS (n = 16), subjects with asymptomatic HIV infection (n = 28), and HIV-seronegative healthy controls (n = 19). SIgA was significantly reduced in the AIDS group (10.4 micrograms/ml) compared with the asymptomatic HIV-infected subjects (17.1 micrograms/ml) and the controls (23.0 micrograms/ml). This decrease comprised both IgA1 and IgA2 to a similar extent on a relative basis. The SIgA decrease in AIDS patients was in striking contrast to their serum IgA level, which was significantly increased (6.9 g/l) compared with the asymptomatic HIV-infected subjects (2.9 g/l) as well as the controls (2.8 g/l). Low parotid output of SIgA in patients with HIV infection was associated with low numbers of CD4+ lymphocytes in peripheral blood as well as the presence of oral infections. The parotid output of IgM was similar in all groups. A low level of SIgA in the external secretions of patients with AIDS may well contribute to their frequent mucosal infections of opportunistic microorganisms. PMID:1899629

  19. Type I receptors in parotid, colon, and pituitary are aldosterone selective in vivo

    SciTech Connect

    Sheppard, K.; Funder, J.W. )

    1987-10-01

    Previous in vivo studies have demonstrated that type I receptors in the rat kidney are aldosterone selective, whereas those in the hippocampus do not appear to discriminate between aldosterone and corticosterone. The authors have injected mature rats with ({sup 3}H)aldosterone or ({sup 3}H)corticosterone plus 100-fold excess of RU 28362, with or without unlabeled aldosterone or corticosterone, and compared type I receptor occupancy in two classic mineralocorticoid target tissues (parotid and colon) and in the pituitary. Mature rats were killed 10-180 min after tracer administration; ({sup 3}H)aldosterone was well taken up and retained in all tissues, whereas ({sup 3}H)corticosterone was significantly retained only in the pituitary 10 min after tracer administration. To assess a possible role for corticosterone-binding globulin (CBG) in conferring aldosterone specificity on type I receptors, 10-day-old rats (with very low levels of CBG) were similarly injected. In the colon and parotid, ({sup 3}H)aldosterone binding was at least an order of magnitude higher than that of corticosterone; in the pituitary aldosterone binding was approximately three times that of corticosterone. They interpret these data as evidence that in the parotid and colon type I receptors are aldosterone selective by a non-CBG-requiring mechanism, whereas in the pituitary there appear to be both aldosterone-selective and nonselective type I sites.

  20. Parotid gland solitary fibrous tumor with mandibular bone destruction and aggressive behavior

    PubMed Central

    González-Otero, Teresa; Castro-Calvo, Alejandro; Ruiz-Bravo, Elena; Burgueño, Miguel

    2014-01-01

    Introduction: Solitary fibrous tumor is associated with serosal surfaces. Location in the salivary glands is extremely unusual. Extrathoracic tumors have an excellent prognosis associated with their benign clinical behavior. We report an aggressive and recurrent case of this tumor. We review the clinical presentation, inmunohistochemical profiles and therapeutic approaches. Case Report: A 73-years-old woman presented a mass in her right parotid gland. She had a past history of right superficial parotidectomy due to a neurilemoma. FNAB and magnetic resonance were non-specific. After a tumor resection, microscopic findings were spindled tumor cells with reactivity to CD34, bcl-2 and CD99 and the tumor was diagnosed as Solitary Fibrous Tumor. The patient suffered two recurrences and the tumor had a histological aggressive behavior and a destruction of the cortical bone of the mandible adjacent to the mass. A marginal mandibulectomy with an alveolar inferior nerve lateralization was performed. Conclusions: Solitary fibrous tumor is a very rare tumor. Usually, they are benign, but occasionally they can be aggressive. Complete resection is the most important prognostic factor and no evidence supports the efficacy of any therapy different to surgery. Due to the unknown prognosis and to the small number of cases reported, a long-term follow-up is guaranteed. Key words:Solitary fibrous tumor, parotid mass, parotid gland, salivary gland, rare tumors. PMID:25136435

  1. Multiple clear-cell sarcomas of small intestine with parotid gland metastasis: A case report

    PubMed Central

    Su, Hao; Liu, Wen-Sheng; Ren, Wen-Hao; Wang, Peng; Shi, Lei; Zhou, Hai-Tao

    2017-01-01

    Clear-cell sarcoma is a rare, malignant soft tissue tumor that displays melanocytic differentiation with a distinct molecular profile. It is rarely localized in the gastrointestinal tract. Herein we reported a case of multiple synchronous clear-cell sarcomas of the gastrointestinal tract with parotid gland metastasis. A 51-year-old male patient presented with a growing painless mass under the right ear. A preoperative positron emission tomography/computed tomography showed multiple intestinal masses and a mass in the right parotid with increased glucose uptake, and he underwent operative treatment with resection of three tumors in the jejunum and ileum and then received a right parotidectomy. Postoperative pathological examination showed that cells in the intestinal tumor were consistent with clear-cell sarcoma of the gastrointestinal tract, and the malignant cells in the parotid gland were similar to the intestinal tumor. Immunohistochemical studies revealed positive expression of HMB-45, Melan-A, and S-100. EWSR1 gene fusion transcripts were undetectable by fluorescence in situ hybridization.

  2. Regulated phosphorylation of secretory granule membrane proteins of the rat parotid gland

    SciTech Connect

    Marino, C.R.; Castle, J.D.; Gorelick, F.S. )

    1990-07-01

    An antiserum raised against purified rat parotid secretory granule membrane proteins has been used to identify organelle-specific protein phosphorylation events following stimulation of intact cells from the rat parotid gland. After lobules were prelabeled with ({sup 32}P)orthophosphate and exposed to secretagogues, phosphoproteins were immunoprecipitated with the granule membrane protein antiserum, separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and visualized by autoradiography. Parallel studies of stimulated amylase release were performed. Isoproterenol treatment of parotid lobules resulted in an increase in the phosphate content of immunoprecipitable 60- and 72-kDa proteins that correlated with amylase release in a time-dependent manner. Forskolin addition mimicked these effects, but only the isoproterenol effects were reversed by propranolol treatment. To confirm the specificity of the antiserum to the secretory granule membrane fraction, subcellular isolation techniques were employed following in situ phosphorylation. The 60- and 72-kDa phosphoproteins were immunoprecipitated from both a particulate fraction and a purified secretory granule fraction. Furthermore, the extraction properties of both species suggest that they are integral membrane proteins. These findings support the possibility that stimulus-regulated secretion may involve phosphorylation of integral membrane proteins of the exocrine secretory granule.

  3. Leiomyosarcoma Ex Pleomorphic Adenoma of the Parotid Gland: A Case Report and Literature Review

    PubMed Central

    Liu, Jingxuan; Marzouk, Mark

    2016-01-01

    There is only one previously reported incident in the English literature of sarcoma ex pleomorphic adenoma of the parotid and there are only 8 cases of primary parotid leiomyosarcoma. In our case, a 79-year-old female patient presented to our care with left preauricular pain, swelling, and facial weakness. After CT imaging, she underwent left total parotidectomy. A spindle cell lesion was identified intraoperatively and the facial nerve was sacrificed. Subsequent analysis of the lesion yielded a diagnosis of leiomyosarcoma ex pleomorphic adenoma. After 30 fractions of radiation therapy, scans were negative for tumor. However, 18 months after first experiencing symptoms, she was found to have metastases to the brainstem and lung. When diagnosing sarcoma ex pleomorphic adenoma of the parotid gland, it is important to perform thorough immunohistochemical staining and exclude a previous history of sarcoma or other sources of metastases. Complete resection is critical due to the tumor's local aggressiveness and metastatic potential. Although these tumors are not very responsive to chemotherapy or radiation, adjuvant treatment is commonly used when margins are unclear. PMID:27672466

  4. An unusual case of spleen metastasis from carcinoma ex pleomorphic adenoma of the parotid gland.

    PubMed

    Rossi, Luigi; Giordani, Erika; Fontana, Antonella; Di Cristofano, Claudio; Cavallaro, Giuseppe; Bagni, Oreste; Filippi, Luca; Bianchi, Loredana; Rinaldi, Giulia; Congedi, Francesca Perrone; Papa, Anselmo; Caruso, Davide; Verrico, Monica; Silecchia, Gianfranco; Tomao, Silverio

    2014-01-23

    Carcinoma ex pleomorphic adenoma is a rare tumor arising from the salivary glands that spreads through direct extension, through the lymphatic vessels, and, rarely, hematogenously. When distant metastases have been found, they have been reported mainly in the lung. We present an unusual case of carcinoma ex pleomorphic adenoma of the parotid gland with splenic metastases. The patient presented with a primary carcinoma ex pleomorphic adenoma of the parotid gland and he underwent a total parotidectomy with laterocervical lymphadenectomy ipsilateral and adjuvant radiation therapy to the right parotid area. One year later, the patient showed an ipsilateral supraclavicular lymph node recurrence, treated with surgery and radiation therapy. Two more years later, the patient developed lung and splenic lesions, detected through CT and PET. He underwent splenectomy and pathologic assessment of the specimen showed metastatic carcinoma ex pleomorphic adenoma. To our knowledge, there is no reported case of a carcinoma ex pleomorphic adenoma metastasizing to the spleen. Patients treated for carcinoma ex pleomorphic adenoma should be investigated for distant metastases with a long-term follow-up examination for local and distant metastases and new splenic lesions in these patients should be investigated.

  5. Acquired von Willebrand's disease associated with epithelial myoepithelial carcinoma of the parotid salivary gland

    PubMed Central

    Chilvers, Geoffrey Spencer; Porter, Graham

    2014-01-01

    This is the first case report of a patient with acquired von Willebrand's disease (AvWD) secondary to epithelial myoepithelial carcinoma (EMC) of the parotid salivary gland. This patient presented to haematology following an abnormal bleeding episode with von Willebrand factor Ristocetin cofactor (VWF:RCo) <5% and VWF:Ag 13%. He was diagnosed with AvWD. At the same time he was found to have a left parotid lump which was excised following a multidisciplinary team meeting. This was histologically reported as an EMC. Following excision, unusually this patient's AvWD did not resolve. Extensive investigation looking for other causes of the AvWD did not reveal any other potential cause; therefore, due to the similar timing of onset of both pathologies it is felt that the AvWD in this case is secondary to the EMC. This case report highlights the presentation, investigation and management of AvWD and parotid lumps as well as discussing proposed pathophysiological mechanisms for AvWD. PMID:25096657

  6. Assessment of absorbed dose to thyroid, parotid and ovaries in patients undergoing Gamma Knife radiosurgery

    NASA Astrophysics Data System (ADS)

    Hasanzadeh, H.; Sharafi, A.; Allah Verdi, M.; Nikoofar, A.

    2006-09-01

    Stereotactic radiosurgery was originally introduced by Lars Leksell in 1951. This treatment refers to the noninvasive destruction of an intracranial target localized stereotactically. The purpose of this study was to identify the dose delivered to the parotid, ovaries, testis and thyroid glands during the Gamma Knife radiosurgery procedure. A three-dimensional, anthropomorphic phantom was developed using natural human bone, paraffin and sodium chloride as the equivalent tissue. The phantom consisted of a thorax, head and neck and hip. In the natural places of the thyroid, parotid (bilateral sides) and ovaries (midline), some cavities were made to place TLDs. Three TLDs were inserted in a batch with 1 cm space between the TLDs and each batch was inserted into a single cavity. The final depth of TLDs was 3 cm from the surface for parotid and thyroid and was 15 cm for the ovaries. Similar batches were placed superficially on the phantom. The phantom was gamma irradiated using a Leksell model C Gamma Knife unit. Subsequently, the same batches were placed superficially over the thyroid, parotid, testis and ovaries in 30 patients (15 men and 15 women) who were undergoing radiosurgery treatment for brain tumours. The mean dosage for treating these patients was 14.48 ± 3.06 Gy (10.5-24 Gy) to a mean tumour volume of 12.30 ± 9.66 cc (0.27-42.4 cc) in the 50% isodose curve. There was no significant difference between the superficial and deep batches in the phantom studies (P-value < 0.05). The mean delivered doses to the parotid, thyroid, ovaries and testis in human subjects were 21.6 ± 15.1 cGy, 9.15 ± 3.89 cGy, 0.47 ± 0.3 cGy and 0.53 ± 0.31 cGy, respectively. The data can be used in making decisions for special clinical situations such as treating pregnant patients or young patients with benign lesions who need radiosurgery for eradication of brain tumours.

  7. Assessment of absorbed dose to thyroid, parotid and ovaries in patients undergoing Gamma Knife radiosurgery.

    PubMed

    Hasanzadeh, H; Sharafi, A; Allah Verdi, M; Nikoofar, A

    2006-09-07

    Stereotactic radiosurgery was originally introduced by Lars Leksell in 1951. This treatment refers to the noninvasive destruction of an intracranial target localized stereotactically. The purpose of this study was to identify the dose delivered to the parotid, ovaries, testis and thyroid glands during the Gamma Knife radiosurgery procedure. A three-dimensional, anthropomorphic phantom was developed using natural human bone, paraffin and sodium chloride as the equivalent tissue. The phantom consisted of a thorax, head and neck and hip. In the natural places of the thyroid, parotid (bilateral sides) and ovaries (midline), some cavities were made to place TLDs. Three TLDs were inserted in a batch with 1 cm space between the TLDs and each batch was inserted into a single cavity. The final depth of TLDs was 3 cm from the surface for parotid and thyroid and was 15 cm for the ovaries. Similar batches were placed superficially on the phantom. The phantom was gamma irradiated using a Leksell model C Gamma Knife unit. Subsequently, the same batches were placed superficially over the thyroid, parotid, testis and ovaries in 30 patients (15 men and 15 women) who were undergoing radiosurgery treatment for brain tumours. The mean dosage for treating these patients was 14.48 +/- 3.06 Gy (10.5-24 Gy) to a mean tumour volume of 12.30 +/- 9.66 cc (0.27-42.4 cc) in the 50% isodose curve. There was no significant difference between the superficial and deep batches in the phantom studies (P-value < 0.05). The mean delivered doses to the parotid, thyroid, ovaries and testis in human subjects were 21.6 +/- 15.1 cGy, 9.15 +/- 3.89 cGy, 0.47 +/- 0.3 cGy and 0.53 +/- 0.31 cGy, respectively. The data can be used in making decisions for special clinical situations such as treating pregnant patients or young patients with benign lesions who need radiosurgery for eradication of brain tumours.

  8. Alcohol oxidizing enzymes and ethanol-induced cytotoxicity in rat pancreatic acinar AR42J cells.

    PubMed

    Bhopale, Kamlesh K; Falzon, Miriam; Ansari, G A S; Kaphalia, Bhupendra S

    2014-04-01

    Alcoholic chronic pancreatitis (ACP) is a serious inflammatory disease causing significant morbidity and mortality. Due to lack of a suitable animal model, the underlying mechanism of ACP is poorly understood. Chronic alcohol abuse inhibits alcohol dehydrogenase (ADH) and facilitates nonoxidative metabolism of ethanol to fatty acid ethyl esters (FAEEs) in the pancreas frequently damaged during chronic ethanol abuse. Earlier, we reported a concentration-dependent formation of FAEEs and cytotoxicity in ethanol-treated rat pancreatic tumor (AR42J) cells, which express high FAEE synthase activity as compared to ADH and cytochrome P450 2E1. Therefore, the present study was undertaken to investigate the role of various ethanol oxidizing enzymes in ethanol-induced pancreatic acinar cell injury. Confluent AR42J cells were pre-treated with inhibitors of ADH class I and II [4-methylpyrazole (MP)] or class I, II, and III [1,10-phenanthroline (PT)], cytochrome P450 2E1 (trans-1,2-dichloroethylene) or catalase (sodium azide) followed by incubation with 800 mg% ethanol at 37°C for 6 h. Ethanol metabolism, cell viability, cytotoxicity (apoptosis and necrosis), cell proliferation status, and formation of FAEEs in AR42J cells were measured. The cell viability and cell proliferation rate were significantly reduced in cells pretreated with 1,10-PT + ethanol followed by those with 4-MP + ethanol. In situ formation of FAEEs was twofold greater in cells incubated with 1,10-PT + ethanol and ∼1.5-fold in those treated with 4-MP + ethanol vs. respective controls. However, cells treated with inhibitors of cytochrome P450 2E1 or catalase in combination of ethanol showed no significant changes either for FAEE formation, cell death or proliferation rate. Therefore, an impaired ADH class I-III catalyzed oxidation of ethanol appears to be a key contributing factor in ethanol-induced pancreatic injury via formation of nonoxidative metabolites of ethanol.

  9. Ca²⁺ signaling and regulation of fluid secretion in salivary gland acinar cells.

    PubMed

    Ambudkar, Indu S

    2014-06-01

    Neurotransmitter stimulation of plasma membrane receptors stimulates salivary gland fluid secretion via a complex process that is determined by coordinated temporal and spatial regulation of several Ca(2+) signaling processes as well as ion flux systems. Studies over the past four decades have demonstrated that Ca(2+) is a critical factor in the control of salivary gland function. Importantly, critical components of this process have now been identified, including plasma membrane receptors, calcium channels, and regulatory proteins. The key event in activation of fluid secretion is an increase in intracellular [Ca(2+)] ([Ca(2+)]i) triggered by IP3-induced release of Ca(2+) from ER via the IP3R. This increase regulates the ion fluxes required to drive vectorial fluid secretion. IP3Rs determine the site of initiation and the pattern of [Ca(2+)]i signal in the cell. However, Ca(2+) entry into the cell is required to sustain the elevation of [Ca(2+)]i and fluid secretion. This Ca(2+) influx pathway, store-operated calcium influx pathway (SOCE), has been studied in great detail and the regulatory mechanisms as well as key molecular components have now been identified. Orai1, TRPC1, and STIM1 are critical components of SOCE and among these, Ca(2+) entry via TRPC1 is a major determinant of fluid secretion. The receptor-evoked Ca(2+) signal in salivary gland acinar cells is unique in that it starts at the apical pole and then rapidly increases across the cell. The basis for the polarized Ca(2+) signal can be ascribed to the polarized arrangement of the Ca(2+) channels, transporters, and signaling proteins. Distinct localization of these proteins in the cell suggests compartmentalization of Ca(2+) signals during regulation of fluid secretion. This chapter will discuss new concepts and findings regarding the polarization and control of Ca(2+) signals in the regulation of fluid secretion.

  10. Atp2c2 Is Transcribed From a Unique Transcriptional Start Site in Mouse Pancreatic Acinar Cells.

    PubMed

    Fenech, Melissa A; Sullivan, Caitlin M; Ferreira, Lucimar T; Mehmood, Rashid; MacDonald, William A; Stathopulos, Peter B; Pin, Christopher L

    2016-12-01

    Proper regulation of cytosolic Ca(2+) is critical for pancreatic acinar cell function. Disruptions in normal Ca(2+) concentrations affect numerous cellular functions and are associated with pancreatitis. Membrane pumps and channels regulate cytosolic Ca(2+) homeostasis by promoting rapid Ca(2+) movement. Determining how expression of Ca(2+) modulators is regulated and the cellular alterations that occur upon changes in expression can provide insight into initiating events of pancreatitis. The goal of this study was to delineate the gene structure and regulation of a novel pancreas-specific isoform for Secretory Pathway Ca(2+) ATPase 2 (termed SPCA2C), which is encoded from the Atp2c2 gene. Using Next Generation Sequencing of RNA (RNA-seq), chromatin immunoprecipitation for epigenetic modifications and promoter-reporter assays, a novel transcriptional start site was identified that promotes expression of a transcript containing the last four exons of the Atp2c2 gene (Atp2c2c). This region was enriched for epigenetic marks and pancreatic transcription factors that promote gene activation. Promoter activity for regions upstream of the ATG codon in Atp2c2's 24th exon was observed in vitro but not in in vivo. Translation from this ATG encodes a protein aligned with the carboxy terminal of SPCA2. Functional analysis in HEK 293A cells indicates a unique role for SPCA2C in increasing cytosolic Ca(2+) . RNA analysis indicates that the decreased Atp2c2c expression observed early in experimental pancreatitis reflects a global molecular response of acinar cells to reduce cytosolic Ca(2+) levels. Combined, these results suggest SPCA2C affects Ca(2+) homeostasis in pancreatic acinar cells in a unique fashion relative to other Ca(2+) ATPases. J. Cell. Physiol. 231: 2768-2778, 2016. © 2016 Wiley Periodicals, Inc.

  11. Recurrence in Region of Spared Parotid Gland After Definitive Intensity-Modulated Radiotherapy for Head and Neck Cancer

    SciTech Connect

    Cannon, Donald M.; Lee, Nancy Y.

    2008-03-01

    Purpose: To discuss the implications of three examples of periparotid recurrence after definitive intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC). Methods and Materials: We present 3 patients with HNC who underwent definitive IMRT with concurrent chemotherapy and later had treatment failure in or near a spared parotid gland. Two patients had bilateral multilevel nodal disease, and all had Level II nodal disease ipsilateral to the site of recurrence. The patients were treated using dose-painting IMRT with a dose of 70 Gy to the gross tumor volume and 59.4 Gy or 54 Gy to the high-risk or low-risk clinical tumor volume, respectively. The parotid glands were spared bilaterally. The patients had not undergone any surgical treatment for HNC before radiotherapy. Results: All patients had treatment failure in the region of a spared parotid gland. Failure in the 2 patients with bilateral multilevel nodal involvement occurred in the periparotid lymph nodes. The third patient developed a dermal metastasis near the tail of a spared parotid gland. On pretreatment imaging, the 2 patients with nodal failure had small nonspecific periparotid nodules that showed no hypermetabolic activity on positron emission tomography. Conclusion: For HNC patients receiving definitive IMRT, nonspecific positron emission tomography-negative periparotid nodules on pretreatment imaging should raise the index of suspicion for subclinical disease in the presence of multilevel or Level II nodal metastases. Additional evaluation of such nodules might be indicated before sparing the ipsilateral parotid gland.

  12. Inhibitory effects of sho-seiryu-to on acetylcholine-induced responses in nasal gland acinar cells.

    PubMed

    Ikeda, K; Wu, D Z; Ishigaki, M; Sunose, H; Takasaka, T

    1994-01-01

    Sho-seiryu-to, a traditional Japanese herbal medicine, has been used extensively in the treatment of allergic rhinitis. The effects of Sho-seiryu-to on electrical responses induced by acetylcholine in dissociated nasal gland acinar cells were investigated using patch-clamp and microfluorimetric imaging techniques. The application of Sho-seiryu-to inhibited both K+ and Cl- currents augmented by acetylcholine. The elevation of intracellular Ca2+ and Na+ concentrations induced by acetylcholine was also inhibited by Sho-seriyu-to. These findings suggest that Sho-seiryu-to attenuated the secretion of water and electrolytes from the nasal glands through an anti-cholinergic effect.

  13. Carbachol activates a K+ channel of very small conductance in the basolateral membrane of rat pancreatic acinar cells.

    PubMed

    Köttgen, M; Hoefer, A; Kim, S J; Beschorner, U; Schreiber, R; Hug, M J; Greger, R

    1999-10-01

    Secretion of Cl- requires the presence of a K+ conductance to hyperpolarize the cell, and to provide the driving force for Cl- exit via luminal Cl- channels. In the exocrine pancreas Cl- secretion is mediated by an increase in cytosolic Ca2+ ([Ca2+]i). Two types of Ca2+-activated K+ channels could be shown in pancreatic acinar cells of different species. However, there are no data on Ca2+-activated K+ channels in rat pancreatic acini. Here we examine the basolateral K+ conductance of freshly isolated rat pancreatic acinar cells in cell-attached and cell-excised patch-clamp experiments. Addition of carbachol (CCH, 1 micromol/l) to the bath led to the activation of very small conductance K+ channels in cell-attached patches (n=27), producing a noisy macroscopic outward current. The respective outward conductance increased significantly by a factor of 2.1+/-0.1 (n=27). Noise analysis revealed a Lorentzian noise component with a corner frequency (f(c)) of 30.3+/-3.5 Hz (n=19), consistent with channel activity in these patches. The estimated single-channel conductance was 1.5+/-0.4 pS (n=19). In cell-excised patches (inside out) from cells previously stimulated with CCH, channel activity was only observed in the presence of K+ in the bath solution. Under these conditions f(c) was 47.6+/-11.9 Hz (estimated single-channel conductance 1.1+/-0.2 pS, n=20). The current/voltage relationship of the noise showed weak inward rectification and the reversal potential shifted towards E(K+) when Na+ in the bath was replaced by K+. Channel activity in cell-excised patches was slightly reduced by 10 mmol/l Ba2+ (23.6+/-2.1% of the total outward current) and was completely absent when K+ in the bath was replaced by Na+. Reduction of the [Ca2+]i from 1 mmol/l to 1 micromol/l in cell-excised experiments decreased the current by 52.3+/-12.3% (n=5). Expression of K(v)LQT1, one of the possible candidates for a small-conductance K+ channel in rat pancreatic acinar cells, was shown by reverse

  14. An Experimental Study on Botulinum Toxin Type A for the Treatment of Excessive Secretion after Submandibular Gland Transplantation in Rabbits

    PubMed Central

    Lin, Bo; Wang, Kan

    2016-01-01

    Objectives. To investigate whether botulinum toxin type A (BTXA) could control excessive secretion after submandibular gland (SMG) transplantation in rabbits and its possible mechanisms. Methods. A new SMG transplantation model was established in rabbit. 30 successfully constructed models were randomly assigned to five groups including control group and four experimental groups. Secretion outputs were used to analyze the effect of BTXA injection on excessive secretion. Hematoxylin and eosin (HE) staining, transmission electron microscopy (TEM), Western blot, and immunofluorescence were performed to analyze its possible mechanisms. Results. After BTXA injection, a significant decrease of excessive secretion after SMG transplantation was found in 2 and 4 weeks groups, but no significant effect on 12 and 24 weeks groups. HE and TEM results showed that BTXA led to morphological and ultrastructural changes of acinar cells of transplanted SMG. Western blot results suggested that BTXA decreased the aquaporin-5 (AQP5) protein expression after BTXA injection for 2 and 4 weeks. Immunofluorescence results showed that AQP5 protein was mainly expressed in the cytoplasm after BTXA injection for 2 and 4 weeks, which might indicate that BTXA promoted AQP5 expression from the cell membrane to cytoplasm. Conclusion. BTXA could effectively control excessive secretion after SMG transplantation in rabbits. PMID:27840738

  15. [Possible relation between viruses and oromaxillofacial tumors. III. Demonstration of the SV40 antigen and anti-SV40 antibodies in patients with tumors of the parotid gland].

    PubMed

    Stoian, M; Zaharia, O; Suru, M; Goldstein, I; Nastac, E

    1987-01-01

    SV40 antigen was detected in 7 of 13 malignant tumors developed in the head and neck region. Specific complement fixing antibodies were found in all the patients with the SV40 antigen present in the parotid gland tumoral cells. Incidence of the anti-SV40 complement fixing antibodies in parotid gland tumor bearing patients was of 69.6%.

  16. Reversal of diabetes in rats using GLP-1-expressing adult pancreatic duct-like precursor cells transformed from acinar to ductal cells.

    PubMed

    Lee, Jieun; Wen, Jing; Park, Jeong Youp; Kim, Sun-A; Lee, Eun Jig; Song, Si Young

    2009-09-01

    Pancreatic injury induces replacement of exocrine acinar cells with ductal cells. These ductal cells have the potential to regenerate the pancreas, but their origin still remains unknown. It has been reported that adult pancreatic acinar cells have the potential to transdifferentiate to ductal progenitor cells. In this regards, we established novel adult pancreatic duct-like progenitor cell lines YGIC4 and YGIC5 and assessed the usefulness of these ductal progenitors in the cell therapy of diabetic rats. Acinar cells were cultured from pancreata of male Sprague Dawley rats and gradually attained ductal cell characteristics, such as expression of CK19 and CFTR with a concomitant down-regulation of amylase expression over time, suggesting transdifferentiation from acinar to ductal cells. During cell culture, the expression of Pdx-1, c-Kit, and vimentin peaked and then decreased, suggesting that transdifferentiation recapitulated embryogenesis. Overexpression of pancreas development regulatory genes and CK19, as well as the ability to differentiate into insulin-producing cells, suggests that the YGIC5 cells had characteristics of pancreatic progenitor cells. Finally, YGIC5 cells coexpressing Green fluorescent protein (GFP) and glucagon-like peptide (GLP)-1 under the activation of a zinc-inducible metallothionein promoter were intravenously infused to STZ-induced diabetic rats. Hyperglycemia was ameliorated with elevation of plasma insulin, and GFP-positive donor cells were colocalized in the acinar and islet areas of recipient pancreata following zinc treatment. In conclusion, after establishing pancreatic progenitor cell lines YGIC4 and YGIC5 under the concept of acinar to ductal transdifferentiation in vitro, we demonstrate how these adult pancreatic stem/progenitor cells can be used to regulate adult pancreatic differentiation toward developing therapy for pancreatic disease such as diabetes mellitus.

  17. Automated Segmentation of the Parotid Gland Based on Atlas Registration and Machine Learning: A Longitudinal MRI Study in Head-and-Neck Radiation Therapy

    SciTech Connect

    Yang, Xiaofeng; Wu, Ning; Cheng, Guanghui; Zhou, Zhengyang; Yu, David S.; Beitler, Jonathan J.; Curran, Walter J.; Liu, Tian

    2014-12-01

    Purpose: To develop an automated magnetic resonance imaging (MRI) parotid segmentation method to monitor radiation-induced parotid gland changes in patients after head and neck radiation therapy (RT). Methods and Materials: The proposed method combines the atlas registration method, which captures the global variation of anatomy, with a machine learning technology, which captures the local statistical features, to automatically segment the parotid glands from the MRIs. The segmentation method consists of 3 major steps. First, an atlas (pre-RT MRI and manually contoured parotid gland mask) is built for each patient. A hybrid deformable image registration is used to map the pre-RT MRI to the post-RT MRI, and the transformation is applied to the pre-RT parotid volume. Second, the kernel support vector machine (SVM) is trained with the subject-specific atlas pair consisting of multiple features (intensity, gradient, and others) from the aligned pre-RT MRI and the transformed parotid volume. Third, the well-trained kernel SVM is used to differentiate the parotid from surrounding tissues in the post-RT MRIs by statistically matching multiple texture features. A longitudinal study of 15 patients undergoing head and neck RT was conducted: baseline MRI was acquired prior to RT, and the post-RT MRIs were acquired at 3-, 6-, and 12-month follow-up examinations. The resulting segmentations were compared with the physicians' manual contours. Results: Successful parotid segmentation was achieved for all 15 patients (42 post-RT MRIs). The average percentage of volume differences between the automated segmentations and those of the physicians' manual contours were 7.98% for the left parotid and 8.12% for the right parotid. The average volume overlap was 91.1% ± 1.6% for the left parotid and 90.5% ± 2.4% for the right parotid. The parotid gland volume reduction at follow-up was 25% at 3 months, 27% at 6 months, and 16% at 12 months. Conclusions: We have validated our

  18. Automated Segmentation of the Parotid Gland Based on Atlas Registration and Machine Learning: A Longitudinal MRI Study in Head-and-Neck Radiation Therapy

    PubMed Central

    Yang, Xiaofeng; Wu, Ning; Cheng, Guanghui; Zhou, Zhengyang; Yu, David S.; Beitler, Jonathan J.; Curran, Walter J.; Liu, Tian

    2015-01-01

    Purpose To develop an automated magnetic resonance imaging (MRI) parotid segmentation method to monitor radiation-induced parotid gland changes in patients after head and neck radiation therapy (RT). Methods and Materials The proposed method combines the atlas registration method, which captures the global variation of anatomy, with a machine learning technology, which captures the local statistical features, to automatically segment the parotid glands from the MRIs. The segmentation method consists of 3 major steps. First, an atlas (pre-RT MRI and manually contoured parotid gland mask) is built for each patient. A hybrid deformable image registration is used to map the pre-RT MRI to the post-RT MRI, and the transformation is applied to the pre-RT parotid volume. Second, the kernel support vector machine (SVM) is trained with the subject-specific atlas pair consisting of multiple features (intensity, gradient, and others) from the aligned pre-RT MRI and the transformed parotid volume. Third, the well-trained kernel SVM is used to differentiate the parotid from surrounding tissues in the post-RT MRIs by statistically matching multiple texture features. A longitudinal study of 15 patients undergoing head and neck RT was conducted: baseline MRI was acquired prior to RT, and the post-RT MRIs were acquired at 3-, 6-, and 12-month follow-up examinations. The resulting segmentations were compared with the physicians' manual contours. Results Successful parotid segmentation was achieved for all 15 patients (42 post-RT MRIs). The average percentage of volume differences between the automated segmentations and those of the physicians' manual contours were 7.98% for the left parotid and 8.12% for the right parotid. The average volume overlap was 91.1% ± 1.6% for the left parotid and 90.5% ± 2.4% for the right parotid. The parotid gland volume reduction at follow-up was 25% at 3 months, 27% at 6 months, and 16% at 12 months. Conclusions We have validated our automated

  19. Immunolocalisation of cartilage-derived retinoic acid-sensitive protein in pleomorphic adenoma of the parotid salivary gland.

    PubMed

    Devlin, H; Sloan, P

    2001-02-01

    Pleomorphic adenoma of the parotid salivary glands often contains chondroid elements and may exhibit cartilaginous and osseous differentiation, although the latter is extremely rare. Twenty-nine pleomorphic adenomas (PAs) of the parotid gland were examined immunohistochemically for the distribution of cartilage-derived retinoic acid-sensitive protein (CD-RAP), a recently described marker of chondrocytes, which may be important in the morphogenesis and development of the salivary gland. In the normal parotid gland, the ductal cells expressed CD-RAP, but not the myoepithelial cells. In the pleomorphic salivary adenomas, the duct-like cells, but not the myoepithelial cells, expressed CD-RAP. Since many authorities consider myoepithelial cells to be the source of the chondroid matrix, it is surprising that these cells do not express the chondrocytic marker, CD-RAP. Putative neoplastic myoepithelium in the pleomorphic adenoma and some cells in the myxochondroid areas expressed S-100 and calponin.

  20. A meta-analysis of the efficacy and safety of managing parotid and submandibular sialoliths using sialendoscopy assisted surgery

    PubMed Central

    Jadu, Fatima M.; Jan, Ahmed M.

    2014-01-01

    Objectives: To review the available techniques and procedures for management of parotid and submandibular sialoliths with special emphasis on the efficacy and safety of the most commonly used combination of techniques; namely, sialendoscopy with conservative surgical removal of the stone. Methods: A systematic search of the English literature using MEDLINE, EMBASE, and the Cochrane library databases were conducted at the Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia. Articles between the years 2004 and 2013 were selected on the basis of preset inclusion criteria. Then, they were reviewed against a checklist to assess the evidence of efficacy of therapy or prevention and analyzed for pertinent data. Results: Eleven articles met the inclusion criteria and were reviewed and analyzed. The success rate of sialendoscopy combined with minor surgical removal of parotid and submandibular sialoliths ranges from 69-100%. Conclusion: Sialendoscopy combined with a minor surgical extraction of parotid and submandibular sialoliths is safe and efficacious. PMID:25316462

  1. Oculoscopy in Rabbits and Rodents.

    PubMed

    Jekl, Vladimir; Hauptman, Karel; Knotek, Zdenek

    2015-09-01

    Ophthalmic diseases are common in rabbits and rodents. Fast and definitive diagnosis is imperative for successful treatment of ocular diseases. Ophthalmic examination in rabbits and rodents can be challenging. Oculoscopy offers great magnification for the examination of the ocular structures in such animals, including the evaluation of cornea, anterior eye chamber, limbus, iris, lens, and retina. To date, oculoscopy has been described only sporadically and/or under experimental conditions. This article describes the oculoscopy technique, normal and abnormal ocular findings, and the most common eye disorders diagnosed with the aid of endoscopy in rabbits and rodents.

  2. LOXL2 induces aberrant acinar morphogenesis via ErbB2 signaling

    PubMed Central

    2013-01-01

    Introduction Lysyl oxidase-like 2 (LOXL2) is a matrix-remodeling enzyme that has been shown to play a key role in invasion and metastasis of breast carcinoma cells. However, very little is known about its role in normal tissue homeostasis. Here, we investigated the effects of LOXL2 expression in normal mammary epithelial cells to gain insight into how LOXL2 mediates cancer progression. Methods LOXL2 was expressed in MCF10A normal human mammary epithelial cells. The 3D acinar morphogenesis of these cells was assessed, as well as the ability of the cells to form branching structures on extracellular matrix (ECM)-coated surfaces. Transwell-invasion assays were used to assess the invasive properties of the cells. Clinically relevant inhibitors of ErbB2, lapatinib and Herceptin (traztuzumab), were used to investigate the role of ErbB2 signaling in this model. A retrospective study on a previously published breast cancer patient dataset was carried out by using Disease Specific Genomic Analysis (DSGA) to investigate the correlation of LOXL2 mRNA expression level with metastasis and survival of ErbB2-positive breast cancer patients. Results Fluorescence staining of the acini revealed increased proliferation, decreased apoptosis, and disrupted polarity, leading to abnormal lumen formation in response to LOXL2 expression in MCF10A cells. When plated onto ECM, the LOXL2-expressing cells formed branching structures and displayed increased invasion. We noted that LOXL2 induced ErbB2 activation through reactive oxygen species (ROS) production, and ErbB2 inhibition by using Herceptin or lapatinib abrogated the effects of LOXL2 on MCF10A cells. Finally, we found LOXL2 expression to be correlated with decreased overall survival and metastasis-free survival in breast cancer patients with ErbB2-positive tumors. Conclusions These findings suggest that LOXL2 expression in normal epithelial cells can induce abnormal changes that resemble oncogenic transformation and cancer progression

  3. Calcium and pancreatic secretion-dynamics of subcellur calcium pools in resting and stimulated acinar cells.

    PubMed Central

    Clemente, F; Meldolesi, J

    1975-01-01

    1 Pulse-chase experiments were carried out on pancreatic tissue lobules incubated in vitro, with 45Ca as the tracer, in order to shed some light on the functional significance of the calcium pools associated with the various cell organelles of the acinar cell, especially in relation to stimulus-secretion coupling. 2 The kinetics of tracer uptake and release which were observed in the intact lobules suggest the existence of a number of intracellular pools, whose rate of exchange is slower than that across teh plasmalemma. 3 The various subcellular fractions accumulate the tracer in different amounts: some (rough microsomes and postmicrosomal supernatant) showed little radioactivity and some (smooth microsomes and zymogen granule membranes) were heavily labelled; mitochondria and zymogen granules showed intermediate values. 4 The fractions are heterogeneous also in relation to the time course of uptake and release of the tracer: in rough and smooth microsomes and, especially, in the postmicrosomal supernatant both rates were fast; zymogen granules and zymogen granule membranes showed slow rates of uptake and little release during chase; intermediate rates were found in mitochondria. 5 In agreement with previous findings we observed that in 45Ca preloaded lobules, stimulation of secretion (brought about by the secretagogue polypeptide caerulein) results in an increase of the tracer release which seems to be due primarily to the rise of the intracellular concentration of free Ca2+ and to the consequent increase of the transmembrane Ca2+ efflux. Among the cell fractions isolated from stimulated lobules only the mitochondria exhibited a significantly lower 45Ca level relative to the unstimulated controls. 6 It is concluded that, of the organelle-bound calcium pools, that associated with the mitochondria might be involved in the regulation of the calcium-dependent functions, including stimulus-secretion coupling; the calcium associated with the zymogen granule content

  4. Large Cohort Dose-Volume Response Analysis of Parotid Gland Function After Radiotherapy: Intensity-Modulated Versus Conventional Radiotherapy

    SciTech Connect

    Dijkema, Tim Terhaard, Chris H.J.; Roesink, Judith M.; Braam, Petra M.; Gils, Carla H. van; Moerland, Marinus A.; Raaijmakers, Cornelis P.J.

    2008-11-15

    Purpose: To compare parotid gland dose-volume response relationships in a large cohort of patients treated with intensity-modulated (IMRT) and conventional radiotherapy (CRT). Methods and materials: A total of 221 patients (64 treated with IMRT, 157 with CRT) with various head-and-neck malignancies were prospectively evaluated. The distribution of tumor subsites in both groups was unbalanced. Stimulated parotid flow rates were measured before and 6 weeks, 6 months, and 1 year after radiotherapy. Parotid gland dose-volume histograms were derived from computed tomography-based treatment planning. The normal tissue complication probability (NTCP) model proposed by Lyman was fit to the data. A complication was defined as stimulated parotid flow ratio <25% of the pretreatment flow rate. The relative risk of complications was determined for IMRT vs. CRT and adjusted for the mean parotid gland dose using Poisson regression modeling. Results: One year after radiotherapy, NTCP curves for IMRT and CRT were comparable with a TD{sub 50} (uniform dose leading to a 50% complication probability) of 38 and 40 Gy, respectively. Until 6 months after RT, corrected for mean dose, different complication probabilities existed for IMRT vs. CRT. The relative risk of a complication for IMRT vs. CRT after 6 weeks was 1.42 (95% CI 1.21-1.67), after 6 months 1.41 (95% CI; 1.12-1.77), and at 1 year 1.21 (95% CI 0.87-1.68), after correcting for mean dose. Conclusions: One year after radiotherapy, no difference existed in the mean dose-based NTCP curves for IMRT and CRT. Early after radiotherapy (up to 6 months) mean dose based (Lyman) models failed to fully describe the effects of radiotherapy on the parotid glands.

  5. Parotid Gland Dose in Intensity-Modulated Radiotherapy for Head and Neck Cancer: Is What You Plan What You Get?

    SciTech Connect

    O'Daniel, Jennifer C.; Garden, Adam S.; Schwartz, David L.; Wang He; Ang, Kian K.; Ahamad, Anesa; Rosenthal, David I.; Morrison, William H.; Asper, Joshua A.; Zhang Lifei; Tung Shihming; Mohan, Radhe; Dong Lei

    2007-11-15

    Purpose: To quantify the differences between planned and delivered parotid gland and target doses, and to assess the benefits of daily bone alignment for head and neck cancer patients treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: Eleven head and neck cancer patients received two CT scans per week with an in-room CT scanner over the course of their radiotherapy. The clinical IMRT plans, designed with 3-mm to 4-mm planning margins, were recalculated on the repeat CT images. The plans were aligned using the actual treatment isocenter marked with radiopaque markers (BB) and bone alignment to the cervical vertebrae to simulate image-guided setup. In-house deformable image registration software was used to map daily dose distributions to the original treatment plan and to calculate a cumulative delivered dose distribution for each patient. Results: Using conventional BB alignment led to increases in the parotid gland mean dose above the planned dose by 5 to 7 Gy in 45% of the patients (median, 3.0 Gy ipsilateral, p = 0.026; median, 1.0 Gy contralateral, p = 0.016). Use of bone alignment led to reductions relative to BB alignment in 91% of patients (median, 2 Gy; range, 0.3-8.3 Gy; 15 of 22 parotids improved). However, the parotid dose from bone alignment was still greater than planned (median, 1.0 Gy, p = 0.007). Neither approach affected tumor dose coverage. Conclusions: With conventional BB alignment, the parotid gland mean dose was significantly increased above the planned mean dose. Using daily bone alignment reduced the parotid dose compared with BB alignment in almost all patients. A 3- to 4-mm planning margin was adequate for tumor dose coverage.

  6. Lycopene protects pancreatic acinar cells against severe acute pancreatitis by abating the oxidative stress through JNK pathway.

    PubMed

    Lv, J C; Wang, G; Pan, S H; Bai, X W; Sun, B

    2015-02-01

    This study investigated the anti-oxidative and anti-inflammatory effects of lycopene on severe acute pancreatitis (SAP) in both in vivo and in vitro models. Utilizing a rat model, we found that lycopene administration protected against SAP, as indicated by the decreased levels of serum amylase and C-reactive protein. Pathological changes were alleviated by pretreatment with lycopene. The serum levels of tumor necrosis factor-α, interleukin-6, macrophage inflammatory protein-1α, and monocyte chemotactic protein-1 were decreased by lycopene. The decreased reactive oxygen species (ROS) content in the pancreatic tissues of the lycopene-treated group were indirectly evaluated by measuring the levels of myeloperoxidase, lipid peroxidase, and superoxide dismutase. Lycopene protected acinar cells against necrosis and apoptosis by relieving the mitochondrial and endoplasmic stress caused by ROS which was shown in electron microscopy and immunohistochemistry staining of active nuclear factor-κB p65. The protective effect was also observed in a simulated SAP model in a rat acinar cell line. ROS and apoptotic staining were compared between groups. Lycopene exerts protective effects against SAP in rats that may be related to its anti-inflammatory property through inhibiting the expression of damage-associated molecular patterns, and anti-oxidative property which can thus maintain cellular homeostasis and prevent the phosphorylation of JNK pathway.

  7. Beneficial effect of the bioflavonoid quercetin on cholecystokinin-induced mitochondrial dysfunction in isolated rat pancreatic acinar cells.

    PubMed

    Weber, Heike; Jonas, Ludwig; Wakileh, Michael; Krüger, Burkhard

    2014-03-01

    The pathogenesis of acute pancreatitis (AP) is still poorly understood. Thus, a reliable pharmacological therapy is currently lacking. In recent years, an impairment of the energy metabolism of pancreatic acinar cells, caused by Ca(2+)-mediated depolarization of the inner mitochondrial membrane and a decreased ATP supply, has been implicated as an important pathological event. In this study, we investigated whether quercetin exerts protection against mitochondrial dysfunction. Following treatment with or without quercetin, rat pancreatic acinar cells were stimulated with supramaximal cholecystokinin-8 (CCK). CCK caused a decrease in the mitochondrial membrane potential (MMP) and ATP concentration, whereas the mitochondrial dehydrogenase activity was significantly increased. Quercetin treatment before CCK application exerted no protection on MMP but increased ATP to a normal level, leading to a continuous decrease in the dehydrogenase activity. The protective effect of quercetin on mitochondrial function was accompanied by a reduction in CCK-induced changes to the cell membrane. Concerning the molecular mechanism underlying the protective effect of quercetin, an increased AMP/ATP ratio suggests that the AMP-activated protein kinase system may be activated. In addition, quercetin strongly inhibited CCK-induced trypsin activity. The results indicate that the use of quercetin may be a therapeutic strategy for reducing the severity of AP.

  8. Parotid gland tumours in a West Indian population: Comparison to world trends

    PubMed Central

    RAMDASS, MICHAEL J.; MAHARAJ, KHEMANAND; MOOTEERAM, JUSTIN; DWARIKA, WENDELL; TILLUCKDHARRY, CLYDE; BARROW, SHAHEEBA

    2015-01-01

    The epidemiology of parotid gland tumours in Trinidad and Tobago and the wider Caribbean is currently unknown. Therefore, an analysis of the pathological records was conducted to determine the pattern of this disease in Trinidad and Tobago. A retrospective analysis was conducted on all parotid gland tumours and the demographic and histological data were analysed. Data from 60 cases were collected over a period of 8 years (October, 2003 to February, 2012), including 56 primary and 4 secondary tumours (1 basal cell carcinoma and 3 metastatic tumours). The patients included 31 men and 29 women, with a mean age of 48.7 years and an age range of 21–73 years (peak age, 51–60 years). The surgical interventions included 53 superficial parotidectomies, 6 radical parotidectomies and 1 biopsy. Of the 56 primary tumours, 41 were benign [34 pleomorphic adenomas and 7 Warthin's tumours (adenolymphomas)], accounting for 73.2% of the cases. The malignant lesions included 6 squamous cell carcinomas, 3 mucoepidermoid carcinomas, 2 acinic cell carcinomas, 2 adenoid cystic carcinomas, 1 anaplastic carcinoma and 1 papillary carcinoma, accounting for 26.8% of the total cases, without any age predominance. The pattern of disease distribution was similar to that indicated by worldwide data, with benign primary lesions accounting for ~80% of the cases (pleomorphic adenomas, 80% and Warthin's tumours, 20%). The most common carcinomas were mucoepidermoid and adenoid cystic types, as indicated by worldwide data; however, in our series, squamous cell carcinoma was the most common type, followed by mucoepidermoid, acinic cell and adenoid cystic carcinomas. The present study will hopefully provide useful information on parotid pathology in Trinidad and Tobago and encourage further research in this field. PMID:25469289

  9. Differential diagnosis of parotid gland tumours: which magnetic resonance findings should be taken in account?

    PubMed

    Tartaglione, T; Botto, A; Sciandra, M; Gaudino, S; Danieli, L; Parrilla, C; Paludetti, G; Colosimo, C

    2015-10-01

    Our aim was to define typical magnetic resonance (MRI) findings in malignant and benign parotid tumours. This study is based on retrospective evaluation of pre-surgical MRI of 94 patients with parotid gland tumours. Histology results were available for all tumours. There were 69 cases of benign (73%) and 25 cases of malignant (27%) tumours, including 44 pleomorphic adenomas, 18 Warthin's tumours, 7 various benign tumours, 6 squamous cell carcinomas, 3 carcinoma ex pleomorphic adenomas, 2 mucoepidermoid carcinomas, 1 adenoid cystic carcinoma and 13 various malignant tumours. The following MRI parameters were evaluated: shape, site, size, margins, signal intensity (SI) on T1w and T2w images, contrast enhancement, signal of cystic content, presence or absence of a capsule, perineural spread, extraglandular growth pattern and cervical adenopathy. Statistical analysis was performed to identify the MRI findings most suggestive of malignancy, and to define the most typical MRI pattern of the most common histologies. Ill-defined margins (p < 0.001), adenopathies (p < 0.001) and infiltrative grown pattern (p < 0.001) were significantly predictive of malignancy. Typical findings of pleomorphic adenoma included hyperintensity on T2w images (p = 0.02), strong contrast enhancement (p < 0.001) and lobulated shape (p = 0.04). Typical findings of Warthin's tumour included hyperintense components on T1w images (p < 0.001), location in the parotid inferior process (p < 0.001) and mild or incomplete contrast enhancement (p = 0.01). SI on T1w and T2w images and contrast enhancement enables differential diagnosis between pleomorphic adenoma and Warthin's tumour.

  10. Effect of fractionated radiotherapy on the parotid gland: an experimental study in Brazilian minipigs

    PubMed Central

    Stramandinoli-Zanicotti, Roberta Targa; Sassi, Laurindo Moacir; Schussel, Juliana Lucena; Torres, Maria Fernanda; Funchal, Melissa; Smaniotto, Gustavo Henrique; Dissenha, José Luis; Carvalho, Andre Lopes

    2013-01-01

    Summary Introduction: Radiotherapy (RT) of head and neck neoplasms often damages the salivary glands. Aim: To examine the pattern of morphologic changes resulting from RT of the head and neck region in minipig parotid glands in a clinical and experimental research setting. Methods: Twelve 18-month-old male Brazilian minipigs weighing 30–40 kg were selected. Eight minipigs were assigned to the experimental group (group 1) and 4 to the control group (group 2). The RT was performed under general anesthesia at Erasto Gaertner Hospital, Curitiba, Brazil, using an á/â ratio of 2.5. The minipigs from group 1 underwent 3 sessions of irradiation with Cobalt 60 of the head and neck, bilaterally, with 3 exposures of 8 Gy each at 7-day intervals for a total dose of 24 Gy. The animals were sacrificed 12 weeks post-RT. Results: The irradiated parotid glands displayed reductions in the size and number of acini as well as loss of secretory granules. The presence of fibrosis and loss of parenchyma relative to non-irradiated glands were observed, with an average reduction in volume of 54%. Conclusions: Our results demonstrate that this model for parotid gland damage resulting from an RT regimen appears to be useful for preclinical large animal studies of RT-induced damage and testing novel potential treatment options. Although recent advances in radiation therapy, such as intensity-modulated radiation therapy, have reduced the dose and limited the field of radiation, considerable salivary gland injury still occurs and can greatly impact the patient's quality of life after cancer treatment. PMID:25992008

  11. Urethral healing in rabbits.

    PubMed

    Scherz, H C; Kaplan, G W; Boychuk, D I; Landa, H M; Haghighi, P

    1992-08-01

    We studied urethral healing in New Zealand white rabbits by histological examination after insult (urethral catheter) or injury (urethrotomy) specifically for acute and chronic inflammation, fibrosis, fistulas, squamous metaplasia, foreign body giant cells and urethral dilatation. Urethral catheterization resulted in increased inflammation and fibrosis compared to noncatheterized animals. Skin closure techniques and materials resulted in an inflammatory response that may extend to and involve the urethra. Minor differences in suture size were not an important variable but the persistence of suture material may have a role in the degree of inflammation and the formation of foreign body giant cells. Transepithelial closure techniques drag epithelial cells into subcutaneous tissues and may predispose to fistula formation.

  12. A comparative study of salivary secretion by parotid and mandibular glands of anaesthetized Capra hircus: effect of pilocarpine.

    PubMed

    Castellano, C; Moreno, M; Raggi, L A; Martinez de Victoria, E; Mataix, F J

    1986-01-01

    A study was made of basal secretion and the effect of the infusion of pilocarpine on the flow and composition of saliva in the parotid and mandibular glands of the anaesthetized lactating goat. In the parotid gland there was a basal flow (1.6 +/- 0.29 microliter/min) which was not present in the mandibular gland. There is a statistically significant dose-effect relationship between pilocarpine and salivary flow in both glands. Salival composition and its variation with respect to the flow of saliva did not conform to either of the two glands to an exclusive monogastric or ruminant model.

  13. Atrophy of myoepithelial cells in parotid glands of diabetic mice; detection using skeletal muscle actin, a novel marker☆

    PubMed Central

    Nashida, Tomoko; Yoshie, Sumio; Haga-Tsujimura, Maiko; Imai, Akane; Shimomura, Hiromi

    2013-01-01

    In mouse parotid glands, we found expression of skeletal muscle actin (actin-α1) protein and mRNA. We isolated myoepithelial cells from the mouse parotid glands and investigated their actin-α1 expression because smooth muscle actin (actin-α2) has been used as a marker for myoepithelial cells. We used actin-α1 expression to identify pathological changes in diabetic non-obese diabetic (NOD; NOD/ShiJcl) mice—a mouse model for Sjögren's syndrome—and found myoepithelial cells to be decreased or atrophied in the diabetic state. PMID:23772384

  14. Management of an unusual case of iatrogenic parotid sialocele using an infant feeding tube: a novel approach

    PubMed Central

    Kulkarni, Ambadas; Chandrasala, Soumithran; Nimbeni, Basavaraj S; Pal Singh, Surendar; Golai, Shruti

    2014-01-01

    Injuries to the parotid duct and parenchyma resulting in swelling in the cheek region commonly present in maxillofacial practice. Sialocele is a discrete collection of saliva in a subcutaneous cavity that can be iatrogenic, idiopathic or the result of post-traumatic injuries to the duct or parenchyma, presenting as a salivary pseudocyst or retention cyst. We present an unusual case of parotid sialocele following surgery for sialolithiasis which presented with progressive painless swelling in the preauricular region of 9 months duration. Treatment included surgical exploration under local anaesthesia and draining the cavity by keeping the opening patent using an infant feeding tube. PMID:25331148

  15. Management of midcheek masses and tumors of the accessory parotid gland.

    PubMed

    De Riu, Giacomo; Meloni, Silvio M; Massarelli, Olindo; Tullio, Antonio

    2011-05-01

    Tumors of the lateral wall of the mouth have different origins and behaviors. These lesions often arise from salivary tissues, such as the accessory parotid gland, but tumors can also originate from the muscles, buccal fat pad, or other structures. Surgical approaches are limited in this region by the presence of the facial nerve and the Stensen's duct. In this article, we present 9 cases of midcheek masses that were operated on via extra- or intraoral approaches. We discuss the problems related to the diagnosis of such tumors, as well as the indications and rationales for different treatment approaches.

  16. Regional radiation dose susceptibility within the parotid gland: Effects on salivary loss and recovery

    SciTech Connect

    Clark, Haley Reinsberg, Stefan; Hovan, Allan; Thomas, Steven; Wu, Jonn

    2015-04-15

    Purpose: Xerostomia is one of the most likely late toxic effects of radiotherapy treatment in patients with head-and-neck cancers. Modern treatment techniques can incorporate knowledge of complication risk into treatment plans. To this end, the authors attempt to quantify the regional radiotherapy dose-dependence of salivary output loss and recovery in a prospective study. Methods: Salivary output was collected from patients undergoing radiotherapy treatment for head-and-neck cancers at the BC Cancer Agency between February 2008 and May 2013. Regional dose-dependence (i.e., dose susceptibility) of loss and recovery is quantified using nonparametric (Spearman’s rank correlation coefficients, local linear regression) and parametric (least-sum of squares, least-median of squares) techniques. Results: Salivary flow recovery was seen in 79 of 102 patients considered (p < 0.0001, Wilcoxon sign rank test). Output loss was strongly correlated with left- and right parotid combined dose φ = min (D{sub L},  45 Gy) + min (D{sub R},  45 Gy), and can be accurately predicted. Median early loss (three months) was 72% of baseline, while median overall loss (1 yr) was 56% of baseline. Fitting an exponential model to whole parotid yields dose sensitivities A{sub 3m} = 0.0604 Gy{sup −1} and A{sub 1y} = 0.0379 Gy{sup −1}. Recovery was not significantly associated with dose. Hints of lateral organ sub-segment dose–response dimorphism were observed. Conclusions: Sub-segmentation appears to predict neither loss nor recovery with any greater precision than whole parotid mean dose, though it is not any worse. Sparing the parotid to a combined dose φ of <50 Gy is recommended for a patient to keep ≈40% of baseline function and thus avoid severe xerostomia at 12 months post-treatment. It seems unlikely that a population’s mean recovery will exceed 20%–30% of baseline output at 1 yr after radiotherapy treatment using current (whole-organ based) clinical guidelines.

  17. Large lipid-rich mammary analogue secretory carcinoma of parotid gland: An unusual case.

    PubMed

    Joshi, Prashant; Mridha, Asit Ranjan; Singh, Shuchita; Kinra, Prateek; Ray, Ruma; Thakar, Alok

    2015-01-01

    Mammary analogue secretory carcinoma (MASC) of the salivary gland is a malignant tumor which bears morphologic, immunohistochemical and molecular features similar to those of mammary secretory carcinoma. The tumor is considered as a low-grade malignancy perhaps slightly more aggressive than acinic cell carcinoma. High-grade transformation with recurrences, regional nodal involvement, metastases, and cancer-related death has been reported in a few cases. We report an unusual case of large MASC of the parotid gland in a young patient without regional lymph node involvement. To the best of our knowledge till date such a large MASC of the salivary gland has not been reported in the English literature.

  18. Sialadenosis of the parotid gland: report of four cases diagnosed by fine-needle aspiration cytology.

    PubMed

    Ascoli, V; Albedi, F M; De Blasiis, R; Nardi, F

    1993-01-01

    Four patients presented with a history of recurrent bilateral swellings of parotid glands. Fine-needle aspiration (FNA) specimens showed highly cellular smears containing clusters of enlarged acini and numerous naked nuclei. A diagnosis consistent with sialadenosis was made considering the distinct morphologic appearance: micrometric measurements in all cases, in addition to histology and electron microscopy in two cases confirmed this hypothesis. A review of clinical histories revealed hormonal, nutritional and neurogenic disorders, which are known to be associated with sialadenosis. In the work-up of salivary gland swellings, it is important to recognize cytologically this underestimated entity, which does not necessarily require surgical treatment.

  19. Lateral facial cleft associated with accessory mandible having teeth, absent parotid gland and peripheral facial weakness.

    PubMed

    Ozçelik, D; Toplu, G; Türkseven, A; Senses, D A; Yiğit, B

    2014-07-01

    Transverse facial cleft is a very rare malformation. The Tessier no. 7 cleft is a lateral facial cleft which emanates from oral cavity and extends towards the tragus, involving both soft tissue and skeletal components. Here, we present a case having transverse facial cleft, accessory mandible having teeth, absent parotid gland and ipsilateral peripheral facial nerve weakness. After surgical repair of the cleft in 2-month of age, improvement of the facial nerve function was detected in 3-year of age. Resection of the accessory mandible was planned in 5-6 years of age.

  20. The cottontail rabbits of Virginia

    USGS Publications Warehouse

    Llewellyn, L.M.; Handley, C.O.

    1945-01-01

    Five races of cottontail rabbits belonging to three species occur in Virginia. One of them, the Mearns cottontail (Sylvilagus floridanus mearnsi), is reported here for the first time. It occurs in six southwestern counties of the state, while the eastern cottontail (S. f. mallurus) occurs in the remainder of the state with the exception of Smith and Fishermans islands off the eastern coast of Cape Charles, where it is replaced by Hitchens cottontail (S. f. hitchensi). The New England cottontail (S. transitionalis) is found on the higher mountain peaks, above 3000 feet, and the swamp rabbit (S. palustris) occurs in the Dismal Swamp region of southeastern Virginia.....The height of the breeding season for the eastern cottontail in Virginia is March and April, but breeding continues through the entire year except in December and January. The average litter size based on embryo counts was 4.7. The sex ratio of 234 specimens from all parts of the state, taken mostly in the December to February period, was 53 males to 47 females. That of a group of 145 rabbits live-trapped at Blacksburg during February and Marchwas 58 males to 42 females. The figures show that males are more active than females during the winter months, and therefore are more easily taken then....In transplanting cottontails from one section of the state to another, it is recommended that only cottontails of the same race as those originally present in the region being restocked be released there....Tularemia is not a common disease among rabbits in Virginia, but the rabbit ticks are often carriers of the disease and may transmit it to rabbits. Rabbit ticks are also found to be carriers of Rocky Mountain fever and American Q. fever. After the ticks drop off the rabbits to hibernate in the ground, which is likely to occur during mid-winter in Virginia, there is relatively little danger of humans contracting tularemia by contact with rabbits. Present laws in Virginia which prohibit rabbit hunting until the

  1. Notch1 is not required for acinar-to-ductal metaplasia in a model of Kras-induced pancreatic ductal adenocarcinoma.

    PubMed

    Avila, Jacqueline L; Troutman, Scott; Durham, Amy; Kissil, Joseph L

    2012-01-01

    Pancreatic ductal adenocarcinoma is believed to arise from precursor lesions termed pancreatic intraepithelial neoplasia (PanIN). Mouse models have demonstrated that targeted expression of activated K-ras to mature acinar cells in the pancreas induces the spontaneous development of PanIN lesions; implying acinar-to-ductal metaplasia (ADM) is a key event in this process. Recent studies suggest Notch signaling is a key regulator of ADM. To assess if Notch1 is required for K-ras driven ADM we employed both an in vivo mouse model and in vitro explant culture system, in which an oncogenic allele of K-ras is activated and Notch1 is deleted simultaneously in acinar cells. Our results demonstrate that oncogenic K-ras is sufficient to drive ADM both in vitro and in vivo but that loss of Notch1 has a minimal effect on this process. Interestingly, while loss of Notch1 in vivo does not affect the severity of PanIN lesions observed, the overall numbers of lesions were greater in mice with deleted Notch1. This suggests Notch1 deletion renders acinar cells more susceptible to formation of K-ras-induced PanINs.

  2. Massive acinar cell apoptosis with secondary necrosis, origin of ducts in atrophic lobules and failure to regenerate in cyanohydroxybutene pancreatopathy in rats

    PubMed Central

    Kelly, Lyndell; Reid, Lynne; Walker, Neal I

    1999-01-01

    Cyanohydroxybutene (CHB), a glycosinolate breakdown product, causes pancreatic injury when given to animals in large amounts. To determine the course of CHB-induced pancreatopathy, rats were given a single subcutaneous dose of CHB and the pancreas weighed and examined by light and electron microscopy and immunohistochemistry at intervals from 2 h to 28 days. The pancreatic lesion was unusual in that there was marked early oedema with limited inflammatory cell infiltration, rapid synchronous onset of acinar cell apoptosis and early advanced atrophy engendering only a limited regenerative response. Acinar cell apoptosis was atypical in that cell fragmentation was limited and phagocytosis delayed, resulting in extensive secondary necrosis. As ducts were unaffected by CHB, the crowded ducts making up the epithelial component of atrophic lobules could be clearly shown to derive from their condensation and proliferation, not the redifferentiation of pre-existing acinar cells, widely held to produce this lesion. Although the basis of CHB selectivity and toxicity for pancreatic acinar cells remains unknown, the potential therapeutic benefit of such an agent in patients with pancreatitis or pancreatic tumours warrants further investigation. PMID:10583631

  3. April 2002: 35-year-old healthy man with enlarging right parotid mass.

    PubMed

    Malcolm, Elsa K; Lopes, M Beatriz S

    2002-10-01

    The April 2002 Case of the Month (COM). 35-year-old healthy man developed a mass in the right parotid gland. A superifical parotidectomy was performed for a 4.5 x 1.5 x 1.5 cm mass involving the intraparotid facial nerve. Grossly the tumor was multinodular, smooth and yellow with normal surrounding salivary gland. Microscopically, the tumor showed expanding nodules composed of proliferating fibroblasts, Schwann cells, and perineural-like cells in a myxoid stroma. Normal peripheral nerve twigs were identified in the periphery of the tumor. There was no increased mitotic activity, cellularity or nuclear pleomorphism. S-100 immunohistochemical stain was positive. The tumor was diagnosed as a solitary plexiform neurofibroma. Plexiform neurofibromas in this area have been described in children with von Recklinghausen's disease or neurofibromatosis 1 (NF 1). Plexiform neurofibromas typically involve deep seated nerve trunks and is considered pathognomonic for NF 1. This unusual case represents a solitary variant of plexiform neurofibroma presenting as a parotid mass in an adult patient without a personal stigmata or family history of NF 1.

  4. ConA and UEA-I lectin histochemistry of parotid gland mucoepidermoid carcinoma.

    PubMed

    Sobral, Ana Paula V; Rego, Moacyr J B M; Cavalacanti, Carmelita L B; Carvalho, Luiz B; Beltrão, Eduardo I C

    2010-03-01

    Mucoepidermoid carcinoma (MEC) corresponds to 5-12% of all salivary gland tumours, and is classified as low, intermediate or high grade. Traditionally, immunohistochemistry was considered as the complementary tool for diagnosis of salivary gland neoplasia. Lectin histochemistry has also been increasingly used in recent years. In this work, lectins were used as histochemical markers for normal and transformed parotid glands. Biopsy specimens of 15 cases diagnosed as MEC (low, intermediate and high grade) of the parotid gland were trypsin- and methanol-H(2)O(2)-treated and incubated with horseradish peroxidase (HRP)-conjugated lectins, Concanavalin A (Con A-HRP) and Ulex europeus I (UEA-I-HRP). Con A stained the neoplasic cells of MEC (all grades). In high and intermediate cases, ductal cells were weakly stained by Con A. UEA-I weakly stained normal cells of the excretory duct and neoplasic cells in high grade. Neoplasic cells in intermediate grade were moderately stained and in low grade, the cell membrane was intensely stained with UEA-I. Stroma presented a direct relation between malignancy and staining intensity for UEA-I. The results indicated that lectin histochemistry distinguished the cell biology among histological grades of MEC.

  5. Development of the glandular epithelium of the bovine parotid gland during ontogenesis.

    PubMed

    Eisenbrückner, A; Fink, C; Kressin, M

    2003-06-01

    The development of the parotid gland was examined in 36 bovine embryos and foetuses with a crown-rump-length (CRL) from 28 up to 1000 mm by light, transmission electron microscopical and actin-immunohistochemical methods. The anlage of the parotid gland in an embryo with 28 mm CRL can be found at the lateral angle of the primitive oral cavity as a local thickening of the epithelium. During the second month, the differentiation of primary ducts and endbuds starts and a lumen develops in the primary ducts. At the end of the second month a lumen appears in the terminal endbuds. In the immature endpiece cells first secretory granules can be seen from a CRL of 240 mm. In the third month differentiation between intra- and inter-lobular ducts is possible. Immature myoepithelial cells present as a basal layer of flattened cells between the epithelial cells and the basement membrane at the end of the second month. During further development they increase in number, become more flattened and form long cellular processes. At the end of the fourth month isolated actin filament bundles are formed, which were also detected by an antibody against smooth muscle actin. The actin filaments condense continuously until they fill the cell processes completely at the end of foetal development.

  6. Quantitative Analysis of Age Specific Variation in the Abundance of Human Female Parotid Salivary Proteins

    PubMed Central

    Ambatipudi, Kiran S.; Lu, Bingwen; Hagen, Fred K; Melvin, James E.; Yates, John R.

    2010-01-01

    Summary Human saliva is a protein-rich, easily accessible source of potential local and systemic biomarkers to monitor changes that occur under pathological conditions; however little is known about the changes in abundance associated with normal aging. In this study, we performed a comprehensive proteomic profiling of pooled saliva collected from the parotid glands of healthy female subjects, divided into two age groups 1 and 2 (20–30 and 55–65 years old, respectively). Hydrophobic charge interaction chromatography was used to separate high from low abundant proteins prior to characterization of the parotid saliva using multidimensional protein identification technology (MudPIT). Collectively, 532 proteins were identified in the two age groups. Of these proteins, 266 were identified exclusively in one age group, while 266 proteins were common to both groups. The majority of the proteins identified in the two age groups belonged to the defense and immune response category. Of note, several defense related proteins (e.g. lysozyme, lactoferrin and histatin-1) were significantly more abundant in group 2 as determined by G-test. Selected representative mass spectrometric findings were validated by western blot analysis. Our study reports the first quantitative analysis of differentially regulated proteins in ductal saliva collected from young and older female subjects. This study supports the use of high-throughput proteomics as a robust discovery tool. Such results provide a foundation for future studies to identify specific salivary proteins which may be linked to age-related diseases specific to women. PMID:19764810

  7. Radioprotective effect of amifostine on parotid gland functioning is region dependent

    SciTech Connect

    Konings, Antonius W.T. . E-mail: a.w.t.konings@med.umcg.nl; Faber, Hette; Vissink, Arjan; Coppes, Rob P.

    2005-12-01

    Purpose: To investigation the protective ability of amifostine during partial irradiation of the rat parotid gland. Methods and Materials: Single-dose X-ray irradiation was performed by use of collimators with conformal radiation portals for either the 100% volume (15 Gy) or the 50% cranial/caudal partial parotid gland volumes (30 Gy). Amifostine was administered intraperitoneally at a dose of 250 mg per kg body weight, 25 minutes before irradiation. Saliva flow rates, gland weights, and the tissues of the individual lobes were investigated up to 1 year after treatment. Results: A clear protective effect of amifostine was found against loss of saliva flow, the altered appearance of gross morphology, loss of gland weight, and histopathologic changes for the 100% volume gland irradiations and for the 50% volume cranial irradiations but not for the 50% volume caudal irradiations. Conclusions: The protective ability of amifostine is strongly dependent on the irradiated glandular region and observed for later damage only. The major effect of the drug seems to be the prevention of volume effects caused by secondary damage that occurs in shielded parts of the gland. The results of the present study show that understanding of the anatomy and physiology of organs that are to be spared is necessary to ensure optimal preservation of function.

  8. ( sup 3 H)protein secretion in rat parotid gland: Substance P-. beta. -adrenergic synergism

    SciTech Connect

    Dreux, C.; Imhoff, V.; Rossignol, B. )

    1987-12-01

    In parotid fragment ({sup 3}H)protein, secretion induced by substance P was moderate, but strongly Ca dependent. However, secretion induced by isoproterenol was large and Ca independent. Potentiation of protein secretion was observed when substance P (SP) and isoproterenol (ISO) acted together. Addition of 10{sup {minus}8} M SP caused a shift to the left in the secretion dose-response curve caused by ISO, but did not enhance ISO-induced maximal response. The potentiating effect seems to be a postreceptor event, since it can be mimicked by forskolin (FK), known to induce directly cAMP accumulation, thus bypassing the {beta}-adrenergic receptor. The synergism described above was, therefore, investigated at the second messenger production level. Stimulation of parotid gland fragments by simultaneous addition of SP plus ISO or FK did not modify cAMP nor inositol trisphosphate (IP{sub 3}) accumulation induced independently by each secretagogue alone. The ionophore A23187 was also able to potentiate secretion induced by a {beta}-adrenergic agonist, this effect being totally abolished by external calcium omission, thus suggesting a role for external calcium in this potentiation phenomenon. These results suggest that the potentiation phenomenon observed is a postreceptor event that occurs at a step distal from the second messenger production.

  9. Surgical management of pleomorphic adenoma of parotid gland in elderly patients: role of morphological features.

    PubMed

    Guerra, Germano; Testa, Domenico; Montagnani, Stefania; Tafuri, Domenico; Salzano, Francesco Antonio; Rocca, Aldo; Amato, Bruno; Salzano, Giovanni; Dell'Aversana Orabona, Giovanni; Piombino, Pasquale; Motta, Gaetano

    2014-01-01

    The neoplasms of the salivary glands account for 2% of head and neck tumors and the most common form is the Pleomorphic adenoma (PA). Parotid gland is affected from 80% to 90% of cases. In elderly these tumors occur mostly in females. These benign tumors are composed of epithelial and myoepithelial cells that are arranged with various morphological patterns and subtypes. The classification of these tumors is also based on the amount and nature of the stroma. In literature there is an almost complete consensus that, in the major salivary glands, PAs are enclosed by a layer of fibrous tissue often called "capsule" but there is disagreement about the form, extension and thickness of this layer. The treatment is surgical and there are two main different surgical approaches: an enucleation (local dissection) or so-called subtotal superficial parotidectomy and lateral or superficial total parotidectomy. Histopathological characteristics of PAs especially of capsular alterations such as thin capsule areas, capsule-free regions, capsule penetration, satellite nodules and pseudopodia in the different subtypes are important for the choice of surgical treatment and the first explanation for tumor recurrence. In our study we describe a morphological features of 84 cases of pleomorphic adenoma of parotid gland from elderly patients treated by a surgical "enucleation like" method called nucleoresection.

  10. Identification of transcalciferin as a major component of human parotid saliva by crossed immunoelectrophoretic mapping.

    PubMed

    Joneja, J M; Greenstein, P M; Revis, G J; Crowle, A J

    1982-01-01

    Human parotid saliva collected from Stenson's duct during sour candy-stimulated salivation was studied by crossed immunoelectrophoresis (X-IEP). Eleven antigens were identified in a pool of salivas from 10 adult, caucasoid males and females. Four were related to serum antigens, three being previously known: IgG, IgA and albumin. The fourth was identified as Gc globulin, also known by function as transcalciferin. Salivary Gc is electrophoretically different from serum Gc, migrating as an alpha 2-beta component rather than as an alpha 1 globulin. The quantities of 8 of the 11 antigens detected by X-IEP were compared for salivas from 10 subjects. These quantities and their ratios to each other were highly variable, indicating idiosyncratic secretory patterns. Only quantities of amylase were moderately consistent from donor to donor. Quantitatively, Gc is a major antigen in parotid saliva. Large proportions of a salivary antigen, alpha 1c, were found in two of the 10 subjects--adult males who never had developed caries. Among the other 8 subjects, all with caries, proportions of alpha 1c were much lower, and 2 subjects lacked it. None of the other antigens measured showed any correlation with caries resistance. The nature and function of alpha 1c are unknown.

  11. Insulation of a G protein-coupled receptor on the plasmalemmal surface of the pancreatic acinar cell

    PubMed Central

    1995-01-01

    Receptor desensitization is a key process for the protection of the cell from continuous or repeated exposure to high concentrations of an agonist. Well-established mechanisms for desensitization of guanine nucleotide-binding protein (G protein)-coupled receptors include phosphorylation, sequestration/internalization, and down-regulation. In this work, we have examined some mechanisms for desensitization of the cholecystokinin (CCK) receptor which is native to the pancreatic acinar cell, and have found the predominant mechanism to be distinct from these recognized processes. Upon fluorescent agonist occupancy of the native receptor, it becomes "insulated" from the effects of acid washing and becomes immobilized on the surface of the plasma membrane in a time- and temperature-dependent manner. This localization was assessed by ultrastructural studies using a colloidal gold conjugate of CCK, and lateral mobility of the receptor was assessed using fluorescence recovery after photobleaching. Of note, recent application of the same morphologic techniques to a CCK receptor-bearing Chinese hamster ovary cell line demonstrated prominent internalization via the clathrin-dependent endocytic pathway, as well as entry into caveolae (Roettger, B.F., R.U. Rentsch, D. Pinon, E. Holicky, E. Hadac, J.M. Larkin, and L.J. Miller, 1995, J. Cell Biol. 128: 1029-1041). These organelles are not observed to represent prominent compartments for the same receptor to traverse in the acinar cell, although fluorescent insulin is clearly internalized in these cells via receptor-mediated endocytosis. In this work, the rate of lateral mobility of the CCK receptor is observed to be similar in both cell types (1-3 x 10(-10) cm2/s), while the fate of the agonist-occupied receptor is quite distinct in each cell. This supports the unique nature of desensitization processes which occur in a cell-specific manner. A plasmalemmal site of insulation of this important receptor on the pancreatic acinar cell

  12. Chronic alcohol exposure exacerbates inflammation and triggers pancreatic acinar-to-ductal metaplasia through PI3K/Akt/IKK

    PubMed Central

    HUANG, XIN; LI, XUQI; MA, QINGYONG; XU, QINHONG; DUAN, WANXING; LEI, JIANJUN; ZHANG, LUN; WU, ZHENG

    2015-01-01

    Pancreatic acinar-to-ductal metaplasia (ADM) has been identified as an initiating event that can progress to pancreatic intraepithelial neoplasia (PanIN) or pancreatic ductal adenocarcinoma (PDAC). Acini transdifferentiation can be induced by persistent inflammation. Notably, compelling evidence has emerged that chronic alcohol exposure may trigger an inflammatory response of macrophages/monocytes stimulated by endotoxins. In the present study, we aimed to evaluate the role of inflammation induced by chronic alcohol and lipopolysaccharide (LPS) exposure in the progression of pancreatic ADM, as well as to elucidate the possible mechanisms involved. For this purpose, cultured macrophages were exposed to varying doses of alcohol for 1 week prior to stimulation with LPS. Tumor necrosis factor-α (TNF-α) and regulated upon activation, normal T cell expression and secreted (RANTES) expression were upregulated in the intoxicated macrophages with activated nuclear factor-κB (NF-κB). Following treatment with the supernatant of intoxicated macrophages, ADM of primary acinar cells was induced. Furthermore, the expression of TNF-α and RANTES, as well as the phosphatidylinositol-3-kinase (PI3K)/protein kinase B(Akt)/inhibitory κB kinase (IKK) signaling pathway have been proven to be involved in the ADM of acinar cells. Moreover, Sprague-Dawley (SD) rats were employed to further explore the induction of pancreatic ADM by chronic alcohol and LPS exposure in vivo. At the end of the treatment period, a number of physiological parameters, such as body weight, liver weight and pancreatic weight were reduced in the exposed rats. Plasma alcohol concentrations and oxidative stress levels in the serum, as well as TNF-α and RANTES expression in monocytes were also induced following chronic alcohol and LPS exposure. In addition, pancreatic ADM was induced through the PI3K/Akt/IKK signaling pathway by the augmented TNF-α and RANTES expression levels in the exposed rats. Overall, we

  13. Collagen type IV stimulates an increase in intracellular Ca2+ in pancreatic acinar cells via activation of phospholipase C.

    PubMed Central

    Somogyi, L; Lasić, Z; Vukicević, S; Banfić, H

    1994-01-01

    Intracellular Ca2+ responses to extracellular matrix molecules were studied in suspensions of pancreatic acinar cells loaded with Fura-2. Collagen type I, laminin, fibrinogen and fibronectin were unable to raise cytosolic free Ca2+ concentration ([Ca2+]i), whereas collagen type IV, at concentrations from 5 to 50 micrograms/ml, significantly increased it. The effect of collagen type IV was not due to possible contamination with type-I transforming growth factor beta or plasminogen, as neither of these agents was able to increase [Ca2+]i. Using highly specific mass assays, concentrations of inositol lipids, 1,2-diacylglycerol (DAG) and Ins(1,4,5) P3 were measured in pancreatic acinar cells stimulated with collagen type IV. A decrease in the concentrations of PtdIns(4,5) P2 and PtdIns4 P with a concomitant increase in the concentrations of DAG and InsP3 mass were observed, showing that collagen type IV increases [Ca2+]i by activation of phospholipase C. The observed [Ca2+]i signals had two components, the first resulting from Ca2+ release from the intracellular stores, and the second resulting from Ca2+ flux from the extracellular medium through the verapamil-insensitive channels. A tyrosine kinase inhibitor (tyrphostine) was able to block inositol lipid signalling caused by collagen type IV, which together with the insensitivity of this pathway to cholera toxin and pertussis toxin or to preactivation of protein kinase C, the longer duration of the increase in [Ca2+]i and a longer lag period needed for observation of increases in DAG and InsP3 concentration with collagen type IV than with carbachol (50 mM) suggest that activation of phospholipase C by collagen type IV is caused by tyrosine kinase activation. Inositol lipid signalling and increases in [Ca2+]i were also observed with Arg-Gly-Asp (RGD)-containing peptide but not with Arg-Asp-Gly (RDG)-containing peptide. Collagen type IV and RGD-containing peptide, but not carbachol, competed in increasing [Ca2+]i and

  14. Bilateral Basaloid Squamous Cell Carcinoma of the Parotid Gland: A Case Report and Review of the Literature

    PubMed Central

    Rivero, Alexander; Tang, Christopher G; Rasgon, Barry M

    2017-01-01

    Introduction: We describe the first known case of bilateral basaloid squamous cell carcinoma of the parotid gland, and we review existing literature. Case Presentation: A previously healthy, 70-year-old white man presented with a 2-cm enlarging mass in the tail of the right parotid gland. Magnetic resonance imaging and computed tomography showed ipsilateral pathologic adenopathy. Results of fine-needle aspiration revealed a high-grade malignancy with squamous features. The patient underwent a right total parotidectomy and modified radical neck dissection. Final pathologic findings revealed a basaloid squamous cell carcinoma. Four years after the initial resection, the patient presented with an enlarging left parotid mass. Findings of fine-needle aspiration and imaging were similar to those 4 years earlier. The patient received a left total parotidectomy and modified radical neck dissection. Postoperative radiation therapy was performed after each surgical intervention. He remains disease free at 4-year follow-up after the second mass was resected. Discussion: Squamous cell carcinoma with basaloid features is a rare and aggressive type of squamous cell carcinoma. To our knowledge, this is the first case report of bilateral parotid basaloid squamous cell carcinoma. PMID:28333602

  15. Medical Management for the Treatment of Nontuberculous Mycobacteria Infection of the Parotid Gland: Avoiding Surgery May Be Possible

    PubMed Central

    Bouhabel, Sarah; Oughton, Matthew Thomas

    2016-01-01

    Infection with nontuberculous mycobacteria (NTM) is uncommon in the head and neck; therefore there is no clear consensus on treating these infections. Our objective was to report our experience with a unique case of NTM infection of the parotid in an immunocompetent patient, in order to determine appropriate management through our experience with this pathology. A 57-year-old man, known for numerous comorbid diseases, presented to our institution complaining of right parotid swelling and pain. A computed tomography (CT) of the neck showed a multiloculated collection in the inferior portion of the right parotid gland, compatible with abscess formation. This abscess was drained by interventional radiology (IR) but required repeat drainage twice due to lack of initial improvement. He was treated with several antibiotics as culture results initially indicated Gram-positive bacilli and then Mycobacterium species, with final identification by a reference laboratory as Mycobacterium abscessus. Imipenem was initiated with amikacin and clarithromycin. His infection clinically and radiologically resolved after 5 months of antibiotherapy. In our case, the patient improved following intravenous antibiotic therapy. Our experience demonstrates that appropriate antibiotherapy can lead to resolution of Mycobacterium abscessus infection in the parotid without the risks associated with surgical intervention. PMID:27340407

  16. Histological characteristics following a long-term nitrate-rich diet in miniature pigs with parotid atrophy.

    PubMed

    Xia, Dengsheng; Qu, Xingmin; Tran, Simon D; Schmidt, Laura L; Qin, Lizheng; Zhang, Chunmei; Cui, Xiuyu; Deng, Dajun; Wang, Songlin

    2015-01-01

    The aim of this study was to investigate the histological characteristics following a 2-year nitrate-rich diet in miniature pigs with parotid atrophy. Using averages collected data from three time points at 6, 12, and 24 months following the induction of parotid gland atrophy, salivary nitrate levels of the nitrate-diet parotid-atrophied group (17.3 ± 3.9 ng/µl) were close to those of the control group (19.6 ± 5.1 ng/µl). Compared to the control group, the nitrate-diet group had significantly higher nitrate levels in blood (P < 0.05) and urine (P < 0.001). Histological and electron microscopy analyses showed no abnormalities in the organs of experimental or control animals. No significant differences on apoptosis rate were found in liver and kidney tissues between the standard- and nitrate-diet groups. Therefore, dietary nitrate supplementation could restore salivary nitrate levels. High-dose nitrate loading for 2 years had no observed systemic toxicity in miniature pigs with parotid atrophy.

  17. Diffuse large B-cell lymphoma of the parotid gland: Cytological, histopathological, and immunohistochemical features: A rare case report

    PubMed Central

    Andola, Sainath K; Masgal, Meenakshi M; Reddy, Rajeev M

    2016-01-01

    Primary malignant lymphomas of the salivary glands are rare, accounting for 2-5% of salivary gland tumors and 5% of extranodal lymphomas, frequently seen in the parotid gland. There are single case reports mentioned in the literature. Clinical presentation is not characteristic and the disease is often overlooked with delay in diagnosis and treatment. We are reporting a case of bilateral parotid gland lymphoma in a 55-year-old male, presented with bilateral enlarged parotids. Magnetic resonance imaging (MRI) showed bilateral enlarged parotid glands with multiple well-defined intraparotid lesions. Fine Needle Aspiration Cytology (FNAC) of both showed mixed population of lymphoid cells with large monocytoid cells with scant cytoplasm, anisonucleosis with prominent nucleoli, and numerous mitoses suggestive of non-Hodgkin's lymphoma (NHL). Histopathology showed sheets of large lymphoma cells destructing the salivary acini and infiltrating the periparotid fat. Immunohistochemistry (IHC) showed diffuse CD20 positivity, B-cell lymphoma 6 protein (Bcl-6) was focally positive and negative for cluster of differentiation (CD) 3, CD5, CD10, and Multiple myeloma oncogene-1 (MUM1) which led to the diagnosis of NHL-Diffuse large B cell type. PMID:28028340

  18. The contribution of mechanoreceptive neurones in the gingival tissues to the masticatory-parotid salivary reflex in man.

    PubMed

    Scott, B J; Bajaj, J; Linden, R W

    1999-10-01

    The masticatory-parotid salivary reflex has been studied in fully dentate subjects. Salivary flow was recorded by siting a modified Lashley cup over the orifice of the parotid duct on one side of the mouth. Subjects chewed on small pieces of silicone rubber for 1-min periods which resulted in a reflex secretion of parotid saliva. The secretion was greatest when the subject chewed on the same side of the mouth (ipsilateral) as the salivary flow was recorded. Less salivary flow resulted when the subjects chewed on the opposite side of the mouth (contralateral). Selected areas of the buccal or lingual gingival tissues were then anaesthetized on the side ipsilateral to the Lashley cup. Anaesthesia of the lingual and buccal gingival tissues together resulted in a reduction of salivary flow in response to similar chewing cycles. Anaesthesia of the lingual gingival tissues alone also resulted in a reduction of salivary flow, but anaesthesia of the buccal gingival tissues alone did not. During mastication it is likely that mechanoreceptors in the gingival tissues will be stimulated which may result in salivary flow. This requires further study as other mechanoreceptive neurones are also known to be involved in the masticatory-parotid salivary reflex.

  19. Bilateral multiple sialolithiasis of the parotid gland in a patient with Sjögren’s syndrome

    PubMed Central

    Konstantinidis, I; Paschaloudi, S; Triaridis, S; Fyrmpas, G; Sechlidis, S; Constantinidis, J

    2007-01-01

    Summary The presence of multiple calculi in the major salivary glands is an uncommon finding. Sjögren’s syndrome is a chronic autoimmune disease characterized by lymphocyte-mediated destruction of the exocrine glands. The case is presented of a 49-year-old female with Sjögren’s syndrome found to have bilateral multiple sialolithiasis in the parenchyma of the parotid glands. The patient presented with a right sided painful inflamed swelling of the parotid region. Even though she had been diagnosed with primary Sjögren’s syndrome 3 years prior to admission, she did not report any previous episode of sialadenitis. Full blood count showed leukocytosis (white blood cells = 14,900/106L) with neutrophilia (75%). Radiological assessment included ultrasound and computed tomography scan of the parotids which demonstrated intra-parenchymal multiple calculi of both parotid glands and obstruction of the right Stensen’s duct. The patient was treated with intravenous antibiotics and anti-inflammatory drugs. On the second day of hospitalisation, she reported spontaneous extrusion of a calculus during massage of the gland, with immediate relief of symptoms. In patients with Sjögren’s syndrome and radiological findings of calculi in the major salivary glands, close observation is mandatory for better control of recurrent sialadenitis and early recognition of mucosa-associated lymphoid tissue lymphomas. PMID:17601211

  20. Role of protein kinase C in caerulein induced expression of substance P and neurokinin-1-receptors in murine pancreatic acinar cells

    PubMed Central

    Koh, Yung-Hua; Tamizhselvi, Ramasamy; Moochhala, Shabbir; Bian, Jin-Song; Bhatia, Madhav

    2011-01-01

    Substance P (SP) is involved in the pathophysiology of acute pancreatitis (AP) via binding to its high-affinity receptor, neurokinin-1-receptor (NK1R). An up-regulation of SP and NK1R expression was observed in experimental AP and in caerulein-stimulated pancreatic acinar cells. However, the mechanisms that lead to this up-regulation are not fully understood. In this study, we showed the role of protein kinase C (PKC) in caerulein-induced SP and NK1R production in isolated mouse pancreatic acinar cells. Caerulein (10−7 M) stimulation rapidly activated the conventional PKC-α and novel PKC-δ as observed by the phosphorylation of these molecules. Pre-treatment of pancreatic acinar cells with Gö6976 (1–10 nM) and rottlerin (1–10 μM) inhibited PKC-α and PKC-δ phosphorylation, respectively, but not the other way round. At these concentrations used, PKC-α and PKC-δ inhibition reversed the caerulein-induced up-regulation of SP and NK1R, indicating an important role of PKCs in the modulation of SP and NK1R expression. Further experiments looking into signalling mechanisms showed that treatment of pancreatic acinar cells with both Gö6976 and rottlerin inhibited the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Inhibition of PKC-α or PKC-δ also affected caerulein-induced transcription factor activation, as represented by nuclear factor-κB and AP-1 DNA-binding activity. The findings in this study suggested that PKC is upstream of the mitogen-activated protein kinases and transcription factors, which then lead to the up-regulation of SP/NK1R expression in caerulein-treated mouse pancreatic acinar cells. PMID:20973912

  1. Role of protein kinase C in caerulein induced expression of substance P and neurokinin-1-receptors in murine pancreatic acinar cells.

    PubMed

    Koh, Yung-Hua; Tamizhselvi, Ramasamy; Moochhala, Shabbir; Bian, Jin-Song; Bhatia, Madhav

    2011-10-01

    Substance P (SP) is involved in the pathophysiology of acute pancreatitis (AP) via binding to its high-affinity receptor, neurokinin-1-receptor (NK1R). An up-regulation of SP and NK1R expression was observed in experimental AP and in caerulein-stimulated pancreatic acinar cells. However, the mechanisms that lead to this up-regulation are not fully understood. In this study, we showed the role of protein kinase C (PKC) in caerulein-induced SP and NK1R production in isolated mouse pancreatic acinar cells. Caerulein (10(-7) M) stimulation rapidly activated the conventional PKC-α and novel PKC-δ as observed by the phosphorylation of these molecules. Pre-treatment of pancreatic acinar cells with Gö6976 (1-10 nM) and rottlerin (1-10 μM) inhibited PKC-α and PKC-δ phosphorylation, respectively, but not the other way round. At these concentrations used, PKC-α and PKC-δ inhibition reversed the caerulein-induced up-regulation of SP and NK1R, indicating an important role of PKCs in the modulation of SP and NK1R expression. Further experiments looking into signalling mechanisms showed that treatment of pancreatic acinar cells with both Gö6976 and rottlerin inhibited the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Inhibition of PKC-α or PKC-δ also affected caerulein-induced transcription factor activation, as represented by nuclear factor-κB and AP-1 DNA-binding activity. The findings in this study suggested that PKC is upstream of the mitogen-activated protein kinases and transcription factors, which then lead to the up-regulation of SP/NK1R expression in caerulein-treated mouse pancreatic acinar cells.

  2. Radiation-Induced Damage to Microstructure of Parotid Gland: Evaluation Using High-Resolution Magnetic Resonance Imaging

    SciTech Connect

    Kan, Tomoko; Kodani, Kazuhiko; Michimoto, Koichi; Fujii, Shinya; Ogawa, Toshihide

    2010-07-15

    Purpose: To elucidate the radiation-induced damage to the microstructure of the parotid gland using high-resolution magnetic resonance imaging. Methods and Materials: High-resolution magnetic resonance imaging of the parotid gland was performed before radiotherapy (RT) and during the RT period or {<=}3 weeks after RT completion for 12 head-and-neck cancer patients using a 1.5-T scanner with a microscopy coil. The maximal cross-sectional area of the gland was evaluated, and changes in the internal architecture of the gland were assessed both visually and quantitatively. Results: Magnetic resonance images were obtained at a median parotid gland dose of 36 Gy (range, 11-64). According to the quantitative analysis, the maximal cross-sectional area of the gland was reduced, the width of the main duct was narrowed, and the intensity ratio of the main duct lumen to background was significantly decreased after RT (p <.0001). According to the visual assessment, the width of the main duct tended to narrow and the contrast of the duct lumen tended to be decreased, but no significant differences were noted. The visibility of the duct branches was unclear in 10 patients (p = .039), and the septum became dense in 11 patients (p = .006) after RT. Conclusion: High-resolution magnetic resonance imaging is a noninvasive method of evaluating radiation-induced changes to the internal architecture of the parotid gland. Morphologic changes in the irradiated parotid gland were demonstrated during the RT course even when a relatively small dose was delivered to the gland.

  3. The Diagnostic Value of B-Mode Sonography in Differentiation of Malignant and Benign Tumors of the Parotid Gland

    PubMed Central

    Khalife, Ali; Bakhshaee, Mehdi; Davachi, Behrouz; Mashhadi, Leila; Khazaeni, Kamran

    2016-01-01

    Introduction: Different imaging modalities are used to evaluate salivary gland diseases, including tumors. Ultrasonography (US) is the preferred method on account of its ease of use, affordability, safety profile, and good tolerance among patients. The aim of this study was to evaluate the role of US in differentiating malignant from benign parotid tumors, in the context of previous controversy in the literature on this subject. Materials and Methods: A cross-sectional study was performed in patients who presented to Qaem Medical Center with parotid masses and who were candidates for parotidectomy between June 2013 and January 2015. Patients were initially referred for a diagnostic US of the parotid. US examinations were performed and sonographic features were reported. The tumors were then classified as benign or malignanton the basis of literature descriptions of the US features of parotid tumors, and were next diagnosed pathologically. The sensitivity, specificity, positive predictive value, and negative predictive value of US for the purpose of differentiating malignant from benign tumors were then calculated. Results: Twenty-eight patients (aged 18–92 years) underwent US of parotid masses. Twenty-three tumors were diagnosed as benign and five were diagnosed as malignant. The final histopathologic examination showed 21 benign and seven malignant tumors. The sensitivity, specificity, positive predictive value, and negative predictive value of US for differentiating malignant from benign tumors were calculated as 57%, 95%, 80%, and 87%, respectively. Conclusion: US has a high specificity in differentiating between malignant and benign tumors. However, fine needle aspiration or core needle biopsy is advocated for an exact diagnosis. PMID:27738606

  4. Radiation Therapy for Cutaneous Squamous Cell Carcinoma Involving the Parotid Area Lymph Nodes: Dose and Volume Considerations

    SciTech Connect

    Chen, Allen M. Grekin, Roy C.; Garcia, Joaquin; Bucci, Mary K.; Margolis, Lawrence W.

    2007-12-01

    Purpose: The intraparotid and periparotid lymph nodes are the most commonly involved when skin cancer of the head and neck metastasizes beyond the primary site. We sought to report the clinical outcome of patients treated with radiation therapy for parotid-area metastases from cutaneous squamous cell carcinoma of the head and neck. Methods and Materials: The records of 36 patients treated with radiation therapy for cutaneous squamous cell carcinoma involving the parotid-area lymph nodes were reviewed. All patients had clinically N0 necks and were without evidence of distant disease. Thirty patients (83%) were treated postoperatively after gross total tumor resection. Median dose to the parotid area was 60 Gy (range, 50-72 Gy). Treatment of clinically N0 necks consisted of surgical dissection (7 patients), irradiation (15 patients), and observation (14 patients). Results: The 5-year estimate of local (parotid) control was 86% in patients treated using surgery with postoperative therapy and 47% in patients treated using radiation therapy alone. Three of 4 patients with tumors that relapsed locally after surgery and postoperative radiation received a dose of less than 60 Gy. Elective neck irradiation decreased the incidence of subsequent nodal failures from 50% to 0% and significantly improved neck control (p < 0.001). The 5-year overall survival rate was 63%. Conclusions: Surgery followed by radiation therapy to doses of at least 60 Gy results in effective local control for patients with parotid area metastasis from cutaneous squamous cell carcinoma. Routine irradiation of the clinically N0 neck is recommended.

  5. Effects of Baicalin on inflammatory mediators and pancreatic acinar cell apoptosis in rats with sever acute pancreatitis

    PubMed Central

    Xiping, Zhang; Hua, Tian; Hanqing, Chen; Li, Chen; Binyan, Yu; Jing, Ma

    2009-01-01

    BACKGROUND: To investigate the effects of Baicalin and Octreotide on inflammatory mediators and pancreatic acinar cells apoptosis of rats with severe acute pancreatitis (SAP). METHODS: SD rats were randomly divided into sham operated group (I group), model control group (II group), Baicalin treated group (III group) and Octreotide treated group (IV group). Each group was also divided into subgroup of 3, 6 and 12 h (n = 15). The mortality rate, ascites/body weight ratio as well as the level of endotoxin, NO and ET-1 in blood were measured. The pathological severity score of pancreas, apoptotic indexes, and expression levels of Bax and Bcl-2 proteins in each group were investigated. RESULTS: The survival rate of III and IV group has a significant difference compared with II group (P12 h < 0.05). The ascites volume, contents of inflammatory mediators in blood and pathological severity score of pancreas of III and IV group declined at different degrees compared to II group (P < 0.05, P < 0.01 or P < 0.001). Apoptotic index in III group was significantly higher than that in II group at 3 and 6 h (P3, 6 h < 0.05). Apoptotic index in IV group was significantly higher than that in II group at pancreatic tail at 6 h (P6 h < 0.05). Expression level of Bax in III group was significantly higher than that in II group (pancreatic head P3 h,6 h < 0.01, pancreatic tail P3 h < 0.001). CONCLUSIONS: Compared with Octreotide in the treatment of SAP, the protective mechanisms of Baicalin include reducing the excessive inflammatory mediators’ release, inducing the pancreatic acinar cells apoptosis. PMID:21772857

  6. Postnatal Pancreas of Mice Contains Tripotent Progenitors Capable of Giving Rise to Duct, Acinar, and Endocrine Cells In Vitro.

    PubMed

    Ghazalli, Nadiah; Mahdavi, Alborz; Feng, Tao; Jin, Liang; Kozlowski, Mark T; Hsu, Jasper; Riggs, Arthur D; Tirrell, David A; Ku, H Teresa

    2015-09-01

    Postnatal pancreas is a potential source for progenitor cells to generate endocrine β-cells for treating type 1 diabetes. However, it remains unclear whether young (1-week-old) pancreas harbors multipotent progenitors capable of differentiating into duct, acinar, and endocrine cells. Laminin is an extracellular matrix (ECM) protein important for β-cells' survival and function. We established an artificial extracellular matrix (aECM) protein that contains the functional IKVAV (Ile-Lys-Val-Ala-Val) sequence derived from laminin (designated aECM-lam). Whether IKVAV is necessary for endocrine differentiation in vitro is unknown. To answer these questions, we cultured single cells from 1-week-old pancreas in semi-solid media supplemented with aECM-lam, aECM-scr (which contains a scrambled sequence instead of IKVAV), or Matrigel. We found that colonies were generated in all materials. Individual colonies were examined by microfluidic reverse transcription-polymerase chain reaction, immunostaining, and electron microscopy analyses. The majority of the colonies expressed markers for endocrine, acinar, and ductal lineages, demonstrating tri-lineage potential of individual colony-forming progenitors. Colonies grown in aECM-lam expressed higher levels of endocrine markers Insulin1, Insulin2, and Glucagon compared with those grown in aECM-scr and Matrigel, indicating that the IKVAV sequence enhances endocrine differentiation. In contrast, Matrigel was inhibitory for endocrine gene expression. Colonies grown in aECM-lam displayed the hallmarks of functional β-cells: mature insulin granules and glucose-stimulated insulin secretion. Colony-forming progenitors were enriched in the CD133(high) fraction and among 230 micro-manipulated single CD133(high) cells, four gave rise to colonies that expressed tri-lineage markers. We conclude that young postnatal pancreas contains multipotent progenitor cells and that aECM-lam promotes differentiation of β-like cells in vitro.

  7. Reg proteins promote acinar-to-ductal metaplasia and act as novel diagnostic and prognostic markers in pancreatic ductal adenocarcinoma

    PubMed Central

    Zogopoulos, George; Shao, Qin; Dong, Kun; Lv, Fudong; Nwilati, Karam; Gui, Xian-yong; Cuggia, Adeline; Liu, Jun-Li; Gao, Zu-hua

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor. Acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) are both precursor lesions that lead to the development of PDAC. Reg family proteins (Reg1A, 1B, 3A/G, 4) are a group of calcium-dependent lectins that promote islet growth in response to inflammation and/or injuries. The aim of this study was to establish a role for Reg proteins in the development of PDAC and their clinical value as biomarkers. We found that Reg1A and Reg3A/G were highly expressed in the ADM tissues by immunohistochemistry. In the 3-dimensional culture of mouse acinar cells, Reg3A promoted ADM formation with concurrent activation of mitogen-acitvated protein kinase. Upregulation of Reg1A and Reg1B levels was observed as benign ductal epithelium progresses from PanIN to invasive PDAC. Patients with PDAC showed significantly higher serum levels of Reg1A and Reg1B than matching healthy subjects. These results were further validated by the quantification of Reg 1A and 1B mRNA levels in the microdissected tissues (22- and 6-fold increases vs. non-tumor tissues). Interestingly, patients with higher levels of Reg1A and 1B exhibited improved survival rate than those with lower levels. Furthermore, tissue expressions of Reg1A, Reg1B, and Reg4 could differentiate metastatic PDAC in the liver from intrahepatic cholangiocarcinoma with 92% sensitivity and 95% specificity. Overall, our results demonstrate the upregulation of Reg proteins during PDAC development. If validated in larger scale, Reg1A and Reg1B could become clinical markers for detecting early stages of PDAC, monitoring therapeutic response, and/or predicting patient's prognosis. PMID:27788482

  8. Incorporation of (/sup 35/S)sulfate in normal and neoplastic rat pancreatic acinar cells in relationship to cytodifferentiation

    SciTech Connect

    Kanwar, Y.S.; Rao, M.S.; Longnecker, D.S.; Reddy, J.K.

    1984-11-01

    The rates of (/sup 35/S)sulfate incorporation in highly differentiated acinar cells from normal pancreas, moderately differentiated cells of nafenopin-induced transplantable pancreatic carcinoma, and poorly differentiated cells from azaserine-induced transplantable pancreatic carcinoma were examined in an attempt to determine if sulfation is a property of acinar cells with well-developed secretory granules. The cells were dissociated, pulsed with (/sup 35/S)sulfate (specific activity, approximately 1000 Ci/mmol) for 10 and 60 min, and chased with medium containing 100 X excess of cold inorganic sulfate for 0, 15, 60, and 120 min. The cells were then processed for determining their pool size and light and electron microscopic autoradiography. No significant differences among their pool sizes were observed. However, the light microscopic autoradiograms revealed the (/sup 35/S)sulfate incorporation as follows: azaserine-induced transplantable pancreatic carcinoma greater than nafenopin-induced transplantable pancreatic carcinoma greater than normal pancreas. Electron microscopic autoradiograms revealed similar trends. The grain densities (concentration of radiation) were highest in the Golgi regions immediately postpulse (0 min) and gradually shifted toward the secretory granules over a 120-min period. In addition, the grain density values of the secretory granule-rich cells of nafenopin-induced transplantable pancreatic carcinoma were relatively similar to the cells of normal pancreas, whereas the grain density values of secretory granule-deficient cells from this tumor were similar to those of poorly differentiated neoplastic cells of azaserine-induced transplantable pancreatic carcinoma. These results show that poorly differentiated neoplastic cells incorporate more (/sup 35/S)sulfate than do the well-differentiated cells, but the reasons for this unexpected differential incorporation are at present unknown.

  9. HEREDITARY OSTEOPETROSIS OF THE RABBIT

    PubMed Central

    Pearce, Louise; Brown, Wade H.

    1948-01-01

    The manifestations and course of an hereditary disease of the rabbit are reported. The condition is present at birth and is invariably fatal, generally in the 4th and 5th weeks of age. Retardation and eventual cessation of growth with marked reduction in size are conspicuous characteristic symptoms. The condition, which first occurred in the backcross progeny of a pure bred Dutch male rabbit, is inherited. It is determined by the expression of a simple recessive unit factor, affected individuals being homozygous for the factor. Rabbits heterozygous for the factor are identified only by appropriate breeding tests. The condition is not sex-linked. The disease has a remarkable resemblance to osteopetrosis or marble bone disease of infants and children with respect to signs and general course and also, as may be stated in anticipation of later discussions (5, 6), to the characteristic abnormal condition of the skeleton. PMID:18103397

  10. Intensity-Modulated vs. Conformal Radiotherapy of Parotid Gland Tumors: Potential Impact on Hearing Loss

    SciTech Connect

    Lamers-Kuijper, E. Schwarz, M.; Rasch, C.; Mijnheer, B.

    2007-01-01

    In 3-dimensional (3D) conformal radiotherapy of parotid gland tumors, little effort is made to avoid the auditory system or the oral cavity. Damage may occur when the ear is located inside the treatment field. The purpose of this study was to design and evaluate an intensity-modulation radiotherapy (IMRT) class solution, and to compare this technique to a 3D conformal approach with respect to hearing loss. Twenty patients with parotid gland cancer were retrospectively planned with 2 different techniques using the original planning target volume (PTV). First, a conventional technique using a wedged beam pair was applied, yielding a dose distribution conformal to the shape of the PTV. Next, an IMRT technique using a fluence map optimization with predefined constraints was designed. A dose of 66 Gy in the PTV was given at the International Commission on Radiation Units and Measures (ICRU) dose prescription point. Dose-volume histograms of the PTV and organs at risk (OARs), such as auditory system, oral cavity, and spinal cord, were compared. The dose in the OARs was lower in the IMRT plans. The mean volume of the middle ear receiving a dose higher than 50 Gy decreased from 66.5% to 33.4%. The mean dose in the oral cavity decreased from 19.4 Gy to 16.6 Gy. The auditory system can be spared if the distance between the inner ear and the PTV is 0.6 cm or larger, and if the overlap between the middle ear and the PTV is smaller than 10%. The maximum dose in the spinal cord was below 40 Gy in all treatment plans. The mean volume of the PTV receiving less than 95% of the prescribed dose increased in the IMRT plan slightly from 3.3% to 4.3 % (p = 0.01). The mean volume receiving more than 107% increased from 0.9% to 2.5% (p = 0.02). It can be concluded that the auditory system, as well as the oral cavity, can be spared with IMRT, but at the cost of a slightly larger dose inhomogeneity in the PTV. The IMRT technique can therefore, in most cases, be recommended as the treatment

  11. European Rabbits as Reservoir for Coxiella burnetii

    PubMed Central

    González-Barrio, David; Maio, Elisa; Vieira-Pinto, Madalena

    2015-01-01

    We studied the role of European rabbits (Oryctolagus cuniculus) as a reservoir for Coxiella burnetii in the Iberian region. High individual and population seroprevalences observed in wild and farmed rabbits, evidence of systemic infections, and vaginal shedding support the reservoir role of the European rabbit for C. burnetii. PMID:25988670

  12. Primary B-Cell Mucosa-Associated Lymphoid Tissue Lymphoma of the Hard Palate and Parotid Gland: Report of One Case and Review of the Literature

    PubMed Central

    Yonal-Hindilerden, Ipek; Hindilerden, Fehmi; Arslan, Serkan; Turan-Guzel, Nalan; Dogan, Ibrahim Oner; Nalcaci, Meliha

    2016-01-01

    A 61-year-old woman was admitted to our hospital with an ulcerated palate mass and swelling of the right parotid gland. Incisional biopsy from the hard palate revealed an extranodal marginal zone B-cell lymphoma, also called mucosa-associated lymphoid tissue (MALT) lymphoma. Final diagnosis was MALT lymphoma of the parotid gland with concomitant involvement of an extremely seldom site of involvement: the hard palate. To our knowledge, this report illustrates the first case of MALT lymphoma of the hard palate and parotid gland without an underlying autoimmune disease. Rituximab-based combination regimen (R-CHOP) provided complete remission with total regression of mass lesions at the hard palate and parotid gland. At 44-month follow-up, there is no disease relapse. We adressed the manifestations and management of MALT lymphoma patients with involvement of salivary gland and oral cavity. PMID:27738485

  13. Primary B-Cell Mucosa-Associated Lymphoid Tissue Lymphoma of the Hard Palate and Parotid Gland: Report of One Case and Review of the Literature.

    PubMed

    Yonal-Hindilerden, Ipek; Hindilerden, Fehmi; Arslan, Serkan; Turan-Guzel, Nalan; Dogan, Ibrahim Oner; Nalcaci, Meliha

    2016-11-01

    A 61-year-old woman was admitted to our hospital with an ulcerated palate mass and swelling of the right parotid gland. Incisional biopsy from the hard palate revealed an extranodal marginal zone B-cell lymphoma, also called mucosa-associated lymphoid tissue (MALT) lymphoma. Final diagnosis was MALT lymphoma of the parotid gland with concomitant involvement of an extremely seldom site of involvement: the hard palate. To our knowledge, this report illustrates the first case of MALT lymphoma of the hard palate and parotid gland without an underlying autoimmune disease. Rituximab-based combination regimen (R-CHOP) provided complete remission with total regression of mass lesions at the hard palate and parotid gland. At 44-month follow-up, there is no disease relapse. We adressed the manifestations and management of MALT lymphoma patients with involvement of salivary gland and oral cavity.

  14. ptf1a+, ela3l− cells are developmentally maintained progenitors for exocrine regeneration following extreme loss of acinar cells in zebrafish larvae

    PubMed Central

    Schmitner, Nicole; Kohno, Kenji

    2017-01-01

    ABSTRACT The exocrine pancreas displays a significant capacity for regeneration and renewal. In humans and mammalian model systems, the partial loss of exocrine tissue, such as after acute pancreatitis or partial pancreatectomy induces rapid recovery via expansion of surviving acinar cells. In mouse it was further found that an almost complete removal of acinar cells initiates regeneration from a currently not well-defined progenitor pool. Here, we used the zebrafish as an alternative model to study cellular mechanisms of exocrine regeneration following an almost complete removal of acinar cells. We introduced and validated two novel transgenic approaches for genetically encoded conditional cell ablation in the zebrafish, either by caspase-8-induced apoptosis or by rendering cells sensitive to diphtheria toxin. By using the ela3l promoter for exocrine-specific expression, we show that both approaches allowed cell-type-specific removal of >95% of acinar tissue in larval and adult zebrafish without causing any signs of unspecific side effects. We find that zebrafish larvae are able to recover from a virtually complete acinar tissue ablation within 2 weeks. Using short-term lineage-tracing experiments and EdU incorporation assays, we exclude duct-associated Notch-responsive cells as the source of regeneration. Rather, a rare population of slowly dividing ela3l-negative cells expressing ptf1a and CPA was identified as the origin of the newly forming exocrine cells. Cells are actively maintained, as revealed by a constant number of these cells at different larval stages and after repeated cell ablation. These cells establish ela3l expression about 4-6 days after ablation without signs of increased proliferation in between. With onset of ela3l expression, cells initiate rapid proliferation, leading to fast expansion of the ela3l-positive population. Finally, we show that this proliferation is blocked by overexpression of the Wnt-signaling antagonist dkk1b. In

  15. Sialochemistry of whole, parotid, and labial minor gland saliva in patients with oral lichen planus.

    PubMed

    Gandara, B K; Izutsu, K T; Truelove, E L; Mandel, I D; Sommers, E E; Ensign, W Y

    1987-11-01

    This study was undertaken to determine whether oral lichen planus in otherwise healthy patients is associated with sialochemical abnormalities. Unstimulated and stimulated whole saliva, stimulated parotid saliva, and stimulated labial minor gland saliva were collected from 25 patients with oral lichen planus and from 25 age- and sex-matched controls. Flow rate and salivary concentrations of immunoglobulins A and G, albumin, amylase, lysozyme, lactoferrin, and total protein were determined by standard analytical techniques. Concentrations of inorganic components including sodium, potassium, calcium, chloride, and phosphate were also measured. No significant differences were found between the lichen planus patients and the controls. These findings do not support an association between oral lichen planus and salivary dysfunction in otherwise healthy patients.

  16. Preservation of Facial Nerve With Adjuvant Radiotherapy for Recurrent Mammary Analogue Secretory Carcinoma of Parotid Gland.

    PubMed

    Jin, Shufang; Ma, Hailong; He, Yue

    2016-06-01

    Mammary analogue secretory carcinoma of salivary glands harbors the recurrent ETV6-NTRK3 gene fusion because of the translocation t (12; 15) (p13; q25) and resembles breast secretory carcinoma. This tumor composed of papillary, cystic, solid, and cribriform patterns. Immunohistochemically, the tumors are positive for mammaglobin, CK7, CK8, STAT5a, vimentin, and S100. In this report, the authors presented a patient of recurrent parotid gland mammary analogue secretory carcinoma in a 22-year-old woman. The patient received extended parotidectomy with partial adhesive masseter surgery. The facial nerve was preserved during the surgery and adjuvant radiotherapy was performed postoperation. The patient did not suffer local recurrence and facial paralysis in the 18 months follow-up period.

  17. Cytological diagnosis of sialadenosis, sialadenitis, and parotid cysts by fine-needle aspiration biopsy.

    PubMed

    Droese, M

    1981-01-01

    This analysis permits the following conclusions: The value of punctate cytology consists in the possibility to verify the clinical diagnosis of a cyst by aspiration of fluid, and to make a preoperative assessment of the necessity of an operation and its type and extent, if proof of a benign or malignant tumor was obtained by microscopic examination. The diagnostic value of punctate cytology can be increased if after aspiration of cyst fluid also solid tissue components from the region of the cyst are included. Patients whose biopsy aspirates did not give evidence for the presence of a tumor should be reexamined 2-4 weeks later. Operative treatment will not be necessary if the follow-up examination reveals that the parotid swelling has subsided. Without this control investigation, recommended by Zajicek [80], morphological aspects always indicate an operation if tumor-negative biopsies cannot be etiologically classified even though clinical data were included in the diagnostic procedure.

  18. Augmentation of cholinergic-mediated amylase release by forskolin in mouse parotid gland

    SciTech Connect

    Watson, E.L.; Singh, J.C.; Jacobson, K.L.

    1985-12-30

    Cholinergic-mediated amylase release in mouse parotid acini was augmented by forskolin; the potency but not the maximal response to carbachol was altered. Amylase released by carbachol plus forskolin was dependent on extracellular calcium and was mimicked by the calcium ionophore, A23187 plus forskolin. Forskolin was also shown to enhance carbachol-stimulated /sup 45/Ca/sup 2 +/ uptake into isolated acini. Hydroxylamine, nitroprusside, and 8-bromo-c-GMP each in combination with forskolin mimicked the effects of carbachol plus forskolin on amylase release. In the presence of carbachol (10/sup -8/M) forskolin did not augment c-AMP levels. However, in the presence of carbachol (5 x 10/sup -7/ M) or hydroxylamine (50 ..mu..M) forskolin did significantly augment c-AMP accumulation. These results suggest that calcium and c-GMP may mediate the augmentation of cholinergic-mediated amylase release by effects on c-AMP metabolism. 21 references, 1 figure, 3 tables.

  19. A safe transoral surgical approach to parapharyngeal tumor arising from deep lobe of parotid gland.

    PubMed

    Casale, Manuele; Capuano, Francesco; Sabatino, Lorenzo; Pace, Annalisa; Oliveto, Giuseppe; Vella, Paola; Moffa, Antonio; Salvinelli, Fabrizio

    2016-01-01

    The management of parapharyngeal tumor is surgical, but the approach remains a challenge. Attention should be paid to avoidance intra-operative bleeding or cranial nerves damage. We report a case of a 67-year-old male complaining of left-ear fullness. A submucosal mass arising from the lateral wall of oropharynx on the left side was observed. Magnetic resonance imaging detected a mass arising from the parotid gland, in particular from the deep lobe, and a fine needle biopsy was compatible with "Warthin tumor." We performed a mini-invasive transoral approach under magnification, previous isolation of homolateral vessels. The decision on which surgical approach to be used is determined by site, size vascularity, and histology of the tumor. A literature review of the main surgical approaches was performed. We performed a combined transoral dissection under magnification with cervicotomic exposure of the neck vascular bundle allowing to dissect the tumor and manage any intra-operative complications.

  20. Carcinoma ex pleomorphic adenoma of parotid gland with hepatic metastasis: clinic-radiological case report.

    PubMed

    Dhillon, Manu; Tomar, Divya; Sharma, Manu; Goel, Samta; Srivastava, Siddharth

    2014-04-01

    Pleomorphic adenoma originally called the mixed tumour is a neoplasm commonly involving major salivary glands. The spectrum of malignancy in pleomorphic adenoma comprises three distinct entities - Carcinoma ex pleomorphic adenoma, carcinosarcoma and benign metastasising pleomorphic adenoma. Carcinoma ex pleomorphic adenoma consists of pleomorphic adenoma with a malignant epithelial component. Occasionally, carcinomas ex pleomorphic adenoma develops metastasis. Here we are reporting here a case of benign pleomorphic adenoma arising in parotid gland which turned into malignancy after four years. The patient developed facial nerve paralysis suggesting malignant transformation. Along the course of the disease, the patient developed regional metastasis to lymph nodes and neck and distant metastasis to liver. This case report emphasises the role of advanced imaging modalities in the early diagnosis of the condition and evaluation of metastasis. The patients with this condition should be treated early for favorable outcome and investigated for distant metastasis.

  1. Facial extention of ear pathology: infected cholesteatoma causing a parotid abscess

    PubMed Central

    Tornari, Chrysostomos; Pal, Surojit; Lingam, Ravi Kumar; Kalan, Ali

    2015-01-01

    A man in his early 30s presented with right-sided preauricular swelling and facial oedema. He had a history of acid injury to his right ear as a child resulting in pinna deformity and subsequent blind sac closure of the external auditory canal. Imaging showed abnormal ear anatomy and abnormal density of the right parotid gland. Antibiotic therapy prevented progression but did not resolve the symptoms. Therefore, the infected area was surgically drained. This showed an underlying cholesteatoma, a benign but locally destructive condition where keratinising squamous epithelium grows in the middle ear and mastoid. The infected region was drained and the cholesteatoma was excised. This led to full resolution of the infection. The patient is awaiting a follow-up diffusion-weighted MRI. This case was unusual as the disease had extended beyond the ear and we therefore wish to alert clinicians to cholesteatoma as a possible cause of facial swelling. PMID:25795747

  2. Effect of dietary copper on the copper content of urine, parotid saliva, and sweat in humans

    SciTech Connect

    Turnlund, J.R. )

    1989-02-09

    Eleven young men were confined to a metabolic research unit to study the effect of the level of dietary copper (Cu) on Cu metabolism. They were fed a constant diet containing the following three levels of dietary Cu: adequate Cu (1.68 mg/d) for 24 days (MP1), low Cu (0.785 mg/d) for 42 days (MP2), and high Cu (7.53 mg/d) for 24 days (MP3). Urine was collected throughout the study and Cu was determined in 6-day pools from the beginning of the study, the end of each MP, and the midpoint of MP2. Parotid saliva was collected near the end of each MP. Sweat was collected from the upper arm and ancillary area of three subjects for 2-day periods near the end of each MP. Urinary Cu averaged 0.34, 0.34 and 0.33 {mu}mol/d for MP 1, 2, and 3, respectively. Individual averages ranged from 0.16 to 0.39 {mu}mol/d. Parotid saliva Cu averaged 13.4, 13.0, and 12.0 nmol/L for MP 1, 2 and 3, respectively. Individual averages ranged from 6.9 to 17.8 nmol/L. Sweat Cu levels were very low and did not appear to be affected by dietary Cu. The limited data suggest that sweat losses would have little effect on Cu balance. Neither urinary nor salivary Cu was affected by dietary Cu or related to indices of Cu status (serum Cu, ceruloplasmin, or erythrocyte superoxide dismutase). Urinary and salivary Cu differed significantly among individuals. Results suggest that urinary, salivary, and sweat Cu do not play a role in regulating Cu retention or affect Cu status of humans.

  3. Mammary analogue secretory carcinoma of parotid: Is preoperative cytological diagnosis possible?

    PubMed

    Oza, Nikita; Sanghvi, Kintan; Shet, Tanuja; Patil, Asawari; Menon, Santosh; Ramadwar, Mukta; Kane, Shubhada

    2016-06-01

    Mammary analogue secretory carcinoma is a recently recognized tumor of salivary gland with characteristic t(12;15)(q13;q25) that results in ETV6-NTRK3 fusion product. Distinguishing mammary analogue secretory carcinoma from other salivary gland tumors is important. Present study highlights cytologic findings in three cases of mammary analogue secretory carcinoma of parotid which facilitate preoperative diagnosis with the aid of ancillary diagnostic techniques. Fine needle aspiration cytology of parotid was performed on three cases after clinical examination. Immunocytochemistry for mammoglobin and S100 were performed. Parotidectomy was done in all cases. The corresponding hematoxylin and eosin stained slides and blocks of all cases were studied. Molecular analysis was done in one of the cases. Cases 1 and 3 revealed uniform atypical epithelial cells arranged in branching papillary pattern with few cells in microcystic pattern. Case 2 showed atypical cells arranged mainly in loose clusters and few singly dissociated. Individual cells revealed round nuclei, vesicular chromatin, prominent nucleoli and abundant finely vacuolated cytoplasm with metachromasia prominent in May-Grunwald-Giemsa smear (case 3). Characteristic hob-nail cells covering papillae were observed in cases 1 and 3. Immunocytochemistry showed strong positivity for mammoglobin and S100 thereby confirming the diagnosis of mammary analogue secretory carcinoma preoperatively. The diagnosis was in concordance with surgical specimen. Also, characteristic ETV6-NTRK3 translocation was confirmed in case 1. Increased awareness and high index of suspicion is necessary for the upfront diagnosis, more so for the papillary variant of mammary analogue secretory carcinoma. Immunocytochemistry aids in confirming this preoperative diagnosis, based on which treatment can be planned. Diagn. Cytopathol. 2016;44:519-525. © 2016 Wiley Periodicals, Inc.

  4. The (Ca2+ + Mg2+)-stimulated ATPase of the rat parotid endoplasmic reticulum.

    PubMed Central

    Thiyagarajah, P; Lim, S C

    1986-01-01

    A membrane fraction enriched in endoplasmic reticulum was prepared from rat parotid glands by using sucrose-gradient centrifugation. The fraction showed a 10-fold increase in specific activity of NADPH: cytochrome c reductase activity over that of tissue homogenates and minimal contamination with plasma membranes or mitochondria. The endoplasmic reticulum fraction possessed both Mg2+ -stimulated ATPase as well as Ca2+, Mg2+-ATPase [( Ca2+ + Mg2+)-stimulated ATPase]activity. The Ca2+, Mg2+-ATPase required 2-5 mM-Mg2+ for optimal activity and was stimulated by submicromolar concentrations of free Ca2+. The Km for free Ca2+ was 0.55 microM and the average Vmax. was 60 nmol/min per mg of protein. The Km for ATP was 0.11 mM. Other nucleotides, such as GTP, CTP or ADP, could not substitute for ATP in supporting the Ca2+-activated nucleotidase activity. Increasing the K+ concentration from 0 to 100 mM caused a 2-fold activation of the Ca2+, Mg2+-ATPase. Trifluoperazine, W7 [N-(6-aminohexyl)-5-chloronaphthalene-1-sulphonamide] and vanadate inhibited the enzyme. The concentration of trifluoperazine and vanadate required for 50% inhibition of the ATPase were 52 microM and 28 microM respectively. Calmodulin, cyclic AMP, cyclic AMP-dependent protein kinase and inositol 1,4,5-trisphosphate had no effect on the ATPase. The properties of the Ca2+, Mg2+ -ATPase were distinct from those of the Mg2+-ATPase, but comparable with those reported for the parotid endoplasmic-reticulum Ca2+-transport system [Kanagasuntheram & Teo (1982) Biochem. J. 208, 789-794]. The results suggest that the Ca2+, Mg2+-ATPase is responsible for driving the ATP-dependent Ca2+ accumulation by this membrane. PMID:2943271

  5. Specific expression of an A-kinase anchoring protein subtype, AKAP-150, and specific regulatory mechanism for Na(+),K(+)-ATPase via protein kinase A in the parotid gland among the three major salivary glands of the rat.

    PubMed

    Kurihara, Kinji; Nakanishi, Nobuo; Amano, Osamu; Yamamoto, Miyuki; Iseki, Shoichi

    2003-07-15

    We have examined the expression of A-kinase anchoring protein (AKAP) in the three major salivary glands, i.e. the parotid gland (PG), submandibular gland (SMG), and sublingual gland (SLG), of the rat to elucidate the functional relevance between saliva secretion and Na(+),K(+)-ATPase regulation by protein kinase A (PKA)-dependent phosphorylation, since an AKAP subtype, AKAP-150, is known to be involved in the regulation of the ATPase in PG. Although AKAP-150 and its mRNA were clearly detected in the PG, they were hardly detectable in either the SMG or SLG. The membrane-bound form of the RII regulatory subunit of PKA, an index for the total amount of AKAP subtypes and therefore of the anchored PKA holoenzyme, was also undetectable in membranes from the SMG and SLG but was found in the PG; though a substantial and comparable amount of Na(+),K(+)-ATPase was present in all of these membrane preparations. Incubation with [gamma-32P]ATP revealed that Na(+),K(+)-ATPase in the PG membranes was quickly phosphorylated upon the addition of cAMP, whereas the ATPases in the membranes from SMG and SLG were not; though they were readily and equally phosphorylated by the exogenously added PKA catalytic subunit. AKAP-150 in the basolateral membranes of PG acinar cells was co-immunoprecipitated with RII by an anti-RII antiserum; and AKAP-150 and Na(+),K(+)-ATPase were immunohistochemically co-localized predominantly on the basolateral membranes, suggesting a possibility that the ATPase might directly interact with the AKAP to form an ATPase/AKAP/PKA complex or associate with the AKAP, such association being mediated via some scaffolding molecule. Expression of AKAP-150 and quick down-regulation of Na(+),K(+)-ATPase by AKAP-anchored PKA in response to cAMP elevation are characteristics specific to PG among the three major salivary glands, suggesting the presence of PG-specific regulatory mechanisms for saliva production/secretion.

  6. Incorporating single-side sparing in models for predicting parotid dose sparing in head and neck IMRT

    SciTech Connect

    Yuan, Lulin Wu, Q. Jackie; Yin, Fang-Fang; Yoo, David; Jiang, Yuliang; Ge, Yaorong

    2014-02-15

    Purpose: Sparing of single-side parotid gland is a common practice in head-and-neck (HN) intensity modulated radiation therapy (IMRT) planning. It is a special case of dose sparing tradeoff between different organs-at-risk. The authors describe an improved mathematical model for predicting achievable dose sparing in parotid glands in HN IMRT planning that incorporates single-side sparing considerations based on patient anatomy and learning from prior plan data. Methods: Among 68 HN cases analyzed retrospectively, 35 cases had physician prescribed single-side parotid sparing preferences. The single-side sparing model was trained with cases which had single-side sparing preferences, while the standard model was trained with the remainder of cases. A receiver operating characteristics (ROC) analysis was performed to determine the best criterion that separates the two case groups using the physician's single-side sparing prescription as ground truth. The final predictive model (combined model) takes into account the single-side sparing by switching between the standard and single-side sparing models according to the single-side sparing criterion. The models were tested with 20 additional cases. The significance of the improvement of prediction accuracy by the combined model over the standard model was evaluated using the Wilcoxon rank-sum test. Results: Using the ROC analysis, the best single-side sparing criterion is (1) the predicted median dose of one parotid is higher than 24 Gy; and (2) that of the other is higher than 7 Gy. This criterion gives a true positive rate of 0.82 and a false positive rate of 0.19, respectively. For the bilateral sparing cases, the combined and the standard models performed equally well, with the median of the prediction errors for parotid median dose being 0.34 Gy by both models (p = 0.81). For the single-side sparing cases, the standard model overestimates the median dose by 7.8 Gy on average, while the predictions by the combined

  7. An anatomical study of the buccinator muscle fibres that extend to the terminal portion of the parotid duct, and their functional roles in salivary secretion

    PubMed Central

    Kang, Hyo-Chang; Kwak, Hyun-Ho; Hu, Kyung-Seok; Youn, Kwan-Hyun; Jin, Guang-Chun; Fontaine, Christian; Kim, Hee-Jin

    2006-01-01

    Until now there has been no definitive anatomical study describing the area where the parotid duct enters the buccinator muscle. In this study, we performed anatomical and histological examinations to investigate the relationship between the parotid duct and the buccinator muscle. Thirty specimens (including the buccinator and the terminal portion of the parotid duct) were obtained from embalmed Korean cadavers. Dissection was performed on 22 of these specimens, and the remaining eight specimens were prepared for histological examination and stained with haematoxylin–eosin or Gomori trichrome. In all specimens, small, distinct muscle fibres originating from the buccinator muscle extended to and inserted into the terminal portion of the parotid duct. The topography of these fibres varied, and we classified them into three categories according to where they originated. Type I buccinator muscle fibres, which inserted into the terminal portion of the parotid duct, originated simultaneously from the anterior and posterior aspects of the duct (ten cases, 45.5%). Type II fibres originated from the anterior aspect of the duct and inserted into the anterior side of the duct (seven cases, 31.8%). Type III fibres originated from the posterior aspect of the parotid duct and ran anteriorly toward the duct (five cases, 22.7%). These results were confirmed in the histological examination of all eight specimens. Based on these findings, we have proposed a tentative description of the physiological role of the buccinator muscle fibres in salivary secretion and in the formation of the sialoliths. PMID:16637883

  8. Microbiological quality of rabbit meat.

    PubMed

    Rodríguez-Calleja, Jose M; Santos, Jesús A; Otero, Andrés; García-López, María-Luisa

    2004-05-01

    World rabbit meat production is estimated to be over 1 million tons, and Spain is the third largest producer. Although rabbit meat is marketed and consumed worldwide, information on microbiological quality is very scarce. Here, we report indicator organisms, spoilage flora, sensory quality, and some physicochemical traits of 24 h postmortem chilled rabbit carcasses and prepackaged rabbit meat stored chilled in air for 0 to 3 days at the retail level. The mean total bacterial count (4.01 +/- 0.48 log CFU/g) for carcasses dressed at a small abattoir by a manual process was significantly lower (P < 0.05) than that (4.96 +/- 0.90 log CFU/g) for carcasses dressed at a large abattoir in automated slaughter lines. Both groups of carcasses had mean pH values of 5.98. The dominant contaminants on carcasses from the small abattoir were Pseudomonas, lactic acid bacteria, and yeasts. These microorganisms and Brochothrix thermosphacta were dominant on carcasses from the large abattoir. On prepacked hind legs (pH 6.26 +/- 0.18) stored at -1 to +1 degree C (supermarket 1), mean aerobic mesophilic count was 5.87 +/- 1.03 log CFU/g, and the major microbial groups were Pseudomonas, yeasts, lactic acid bacteria, and B. thermosphacta. On prepacked whole carcasses (pH 6.37 +/- 0.18) displayed at -1 to +5 degrees C (supermarket 2), mean aerobic mesophilic count was 6.60 +/- 1.18 and the same microbial groups were dominant. Relative Escherichia coli incidence was supermarket 2 > large abattoir > supermarket 1 > small abattoir. Overall, low numbers of coliforms, Enterobacteriaceae, psychrotrophic clostridia, coagulase-positive staphylococci, and molds were found. Sensory scores, pH values, and L-lactic acid content differentiated fresh carcasses from retail samples. Data obtained suggest that the microflora of chilled rabbit meat are different from those found on the meat of other animals.

  9. Endoscopic ultrasound in the diagnosis of acinar cell carcinoma of the pancreas: contrast-enhanced endoscopic ultrasound, endoscopic ultrasound elastography, and pathological correlation.

    PubMed

    Chantarojanasiri, Tanyaporn; Hirooka, Yoshiki; Kawashima, Hiroki; Ohno, Eizaburo; Yamamura, Takeshi; Funasaka, Kohei; Nakamura, Masanao; Miyahara, Ryoji; Ishigami, Masatoshi; Watanabe, Osamu; Nakaguro, Masato; Shimoyama, Yoshie; Nakamura, Shigeo; Goto, Hidemi

    2016-11-01

    We report a case series of five patients with pancreatic acinar cell carcinoma who received surgical treatment and compared the preoperative contrast-enhanced endoscopic ultrasound (EUS) and EUS elastography patterns with the surgical specimens. The contrast-enhanced EUS indicated vascular tumors with gradual enhancement in four patients and a hypovascular tumor in one patient. The elastography indicated an elastic score of 3 (hard lesion with softer border) in two patients and a score of 5 (hard lesion, which included the surrounding area) in two patients. In tumors with an elastic score of 5, the pathology exhibited abundant hyalinizing fibrous stroma or massive tumor invasion to the surrounding tissue. We concluded that acinar cell carcinoma of the pancreas has various patterns of EUS contrast-enhancement and elastography, depending on the pathologic phenotype.

  10. Endoscopic ultrasound in the diagnosis of acinar cell carcinoma of the pancreas: contrast-enhanced endoscopic ultrasound, endoscopic ultrasound elastography, and pathological correlation

    PubMed Central

    Chantarojanasiri, Tanyaporn; Hirooka, Yoshiki; Kawashima, Hiroki; Ohno, Eizaburo; Yamamura, Takeshi; Funasaka, Kohei; Nakamura, Masanao; Miyahara, Ryoji; Ishigami, Masatoshi; Watanabe, Osamu; Nakaguro, Masato; Shimoyama, Yoshie; Nakamura, Shigeo; Goto, Hidemi

    2016-01-01

    We report a case series of five patients with pancreatic acinar cell carcinoma who received surgical treatment and compared the preoperative contrast-enhanced endoscopic ultrasound (EUS) and EUS elastography patterns with the surgical specimens. The contrast-enhanced EUS indicated vascular tumors with gradual enhancement in four patients and a hypovascular tumor in one patient. The elastography indicated an elastic score of 3 (hard lesion with softer border) in two patients and a score of 5 (hard lesion, which included the surrounding area) in two patients. In tumors with an elastic score of 5, the pathology exhibited abundant hyalinizing fibrous stroma or massive tumor invasion to the surrounding tissue. We concluded that acinar cell carcinoma of the pancreas has various patterns of EUS contrast-enhancement and elastography, depending on the pathologic phenotype. PMID:27853750

  11. Inhibition of eIF2α dephosphorylation inhibits ErbB2-induced deregulation of mammary acinar morphogenesis

    PubMed Central

    Sequeira, Sharon J; Wen, Huei Chi; Avivar-Valderas, Alvaro; Farias, Eduardo F; Aguirre-Ghiso, Julio A

    2009-01-01

    Background The ErbB2/Her2/Neu receptor tyrosine kinase is amplified in ~30% of human breast cancers. Phosphorylation of the translation initiation factor, eIF2α inhibits global protein synthesis and activates a stress signaling and growth suppressive program. We have shown that forced phosphorylation of eIF2α can suppress head and neck, colorectal carcinoma and multiple myeloma tumor growth and/or survival. Here we explore whether ErbB2 modulates eIF2α phosphorylation and whether forced phosphorylation of the latter can antagonize ErbB2 deregulation of mammary acinar morphogenesis. Results We tested whether ErbB2 signaling influenced eIF2α signaling and whether enhanced phosphorylation of the latter affected ErbB2-deregulated mammary acinar development. We obtained stable MCF10A cells overexpressing wild-type (Wt) Neu/ErbB2 or a constitutively active (CA) variant via retroviral delivery or mammary tumor cells from MMTV-Neu tumors. Western blotting, RT-PCR and confocal microscopy were used to analyze the effects of ErbB2 activation on eIF2α signaling and the effect of the GADD34-PP1C inhibitor salubrinal. Wt- and MMTV-Neu cells formed aberrant acini structures resembling DCIS, while CA-ErbB2 overexpression induced invasive lesions. In these structures we found that CA-ErbB2 but not the Wt variant significantly down-regulated the pro-apoptotic gene CHOP. This occurred without apparent modulation of basal phosphorylation of PERK and eIF2α or induction of its downstream target ATF4. However, inhibition of eIF2α dephosphorylation with salubrinal was sufficient to inhibit Wt- and CA-ErbB2- as well as MMTV-Neu-induced deregulation of acinar growth. This was linked to enhanced CHOP expression, inhibition of proliferation, induction of apoptosis and luminal clearing in Wt-ErbB2 and to inhibition of cyclin D1 levels and subsequent proliferation in CA-ErbB2 cells. Conclusion Depending on the strength of ErbB2 signaling there is a differential regulation of CHOP and e

  12. Successful Salvage Chemotherapy with FOLFIRINOX for Recurrent Mixed Acinar Cell Carcinoma and Ductal Adenocarcinoma of the Pancreas in an Adolescent Patient.

    PubMed

    Pfrommer, Sarah; Weber, Achim; Dutkowski, Philipp; Schäfer, Niklaus G; Müllhaupt, Beat; Bourquin, Jean-Pierre; Breitenstein, Stefan; Pestalozzi, Bernhard C; Stenner, Frank; Renner, Christoph; D'Addario, Giannicola; Graf, Hans-Jörg; Knuth, Alexander; Clavien, Pierre-Alain; Samaras, Panagiotis

    2013-01-01

    Pancreatic tumors are rare in children and adolescents. Here, we report the case of a 15-year-old boy who presented with a mixed acinar cell carcinoma/ductal adenocarcinoma with blastomatous components. He received multimodal treatment including various chemotherapy regimens and multistep surgery including liver transplantation. Introduction of FOLFIRINOX after relapse repeatedly achieved a durable metabolic and clinical response with good quality of life.

  13. Successful Salvage Chemotherapy with FOLFIRINOX for Recurrent Mixed Acinar Cell Carcinoma and Ductal Adenocarcinoma of the Pancreas in an Adolescent Patient

    PubMed Central

    Pfrommer, Sarah; Weber, Achim; Dutkowski, Philipp; Schäfer, Niklaus G.; Müllhaupt, Beat; Bourquin, Jean-Pierre; Breitenstein, Stefan; Pestalozzi, Bernhard C.; Stenner, Frank; Renner, Christoph; D'Addario, Giannicola; Graf, Hans-Jörg; Knuth, Alexander; Clavien, Pierre-Alain; Samaras, Panagiotis

    2013-01-01

    Pancreatic tumors are rare in children and adolescents. Here, we report the case of a 15-year-old boy who presented with a mixed acinar cell carcinoma/ductal adenocarcinoma with blastomatous components. He received multimodal treatment including various chemotherapy regimens and multistep surgery including liver transplantation. Introduction of FOLFIRINOX after relapse repeatedly achieved a durable metabolic and clinical response with good quality of life. PMID:24163668

  14. Expression pattern of REIC/Dkk-3 in various cell types and the implications of the soluble form in prostatic acinar development.

    PubMed

    Zhang, Kai; Watanabe, Masami; Kashiwakura, Yuji; Li, Shun-Ai; Edamura, Kohei; Huang, Peng; Yamaguchi, Ken; Nasu, Yasutomo; Kobayashi, Yasuyuki; Sakaguchi, Masakiyo; Ochiai, Kazuhiko; Yamada, Hiroshi; Takei, Kohji; Ueki, Hideo; Huh, Nam-Ho; Li, Ming; Kaku, Haruki; Na, Yanqun; Kumon, Hiromi

    2010-12-01

    The tumor suppressor REIC/Dkk-3 is a secretory protein which was originally identified to be downregulated in human immortalized cells. In the present study, we investigated the expression pattern of REIC/Dkk-3 in various cell types to characterize its physiological functions. We first examined the expression level of REIC/Dkk-3 in a broad range of cancer cell types and confirmed that it was significantly downregulated in all of the cell types. We also examined the tissue distribution pattern in a variety of normal mouse organs. Ubiquitous REIC/Dkk-3 protein expression was observed in the organs. The expression was abundant in the liver, heart and brain tissue, but was absent in the spleen and peripheral blood mononuclear cells. The immunohistochemical analyses revealed that the subcellular localization of REIC/Dkk-3 had a punctate pattern around the nucleus, indicating its association with secretory vesicles. In cancer cells stably transfected with REIC/Dkk-3, the protein was predominantly localized to the endoplasmic reticulum (ER) under observation with confocal microscopy. Because REIC/Dkk-3 was found to be abundantly expressed in the acinar epithelial cells of the mouse prostate, we analyzed the effects of recombinant REIC/Dkk-3 protein on the acinar morphogenesis of RWPE-1 cells, which are derived from human normal prostate epithelium. Statistically significant acinar growth was observed in the culture condition with 10 µg/ml REIC/Dkk-3 protein, implicating the soluble form in prostatic acinar development. Current results suggest that REIC/Dkk-3 may play a role in regulating the morphological process of normal tissue architecture through an autocrine and/or paracrine manner.

  15. Sialolipoma of the parotid gland: Case report with literature review comparing major and minor salivary gland sialolipomas

    PubMed Central

    Qayyum, Sohail; Meacham, Ryan; Sebelik, Merry; Zafar, Nadeem

    2013-01-01

    Sialolipoma is a rare tumor found within both major and minor salivary glands. Here we discuss sialolipoma of the parotid gland and briefly review the English literature. Including our case, a total of 35 sialolipomas have been reported, 18 within major salivary glands and 17 within minor salivary glands. Major gland sialolipomas most often are presented in the parotid gland (77%) and those from minor glands were most often seen in the palate (41%). All lesions were well circumscribed and contained mature adipose tissue intimately admixed with benign salivary gland components. Ductal dilatation was found in 100% of minor salivary gland sialolipomas but in only 28% of major salivary gland tumors. Nerve entrapment has also rarely been noted in major salivary glands (14%) whereas myxoid degeneration has been identified in rare minor salivary glands tumors (13%). Treatment is surgical excision and is curative with no reports of recurrence. PMID:23798838

  16. [Biochemical findings in proteincomposition of secretions of human malignant parotid tumours, chronic parotitis and sialadenoses (author's transl)].

    PubMed

    Eichner, H; Bretzel, G; Hochstrasser, K

    1977-01-01

    In comparison to former investigations in pleomorphic adenoms and Wharthin tumours in the present paper secretion of IgA, lysozyme in correlation to flowrate and total secretion in glands with malignant tumours, inflammations and Sialadenosis were estimated. Thereby 12 patients with malignomas of the parotid gland, 11 patients with chronic parotitis and 12 with sialadenoses were examined. The following results were found: 1. The concentration of protein, IgA and Lysozym is significantly higher than in normal glands and in glands with pleomorphic adenomas and Wharthin tumours. 2. Differentialdiagnosis of Sialadenitis and Sialadenosis of parotid glands is possible by estimating the examined parameters. Thereby in glands with sialadenosis flowrate is higher than in normal glands, and significant lower in glands with sialadenitis. Moreover concentrations of IgA and Lysozyme and protein in glands with sialadenitis are evaluated.

  17. Relapsed Acinic Cell Carcinoma of the Parotid Gland With Diffuse Distant Metastasis: Case Report With Literature Review.

    PubMed

    Khelfa, Yousef; Mansour, Munthir; Abdel-Aziz, Yousef; Raufi, Ali; Denning, Krista; Lebowicz, Yehuda

    2016-01-01

    Acinic cell carcinoma (ACC) is an uncommon salivary gland neoplasm that generally displays an indolent growth pattern. Most cases arise in the major glands, particularly the parotid. However, it can arise from minor salivary glands in the oral cavity and aero-digestive tract. Although ACC is generally a low-grade malignant tumor, poorly differentiated and high-grade transformed variants exhibit a propensity for late recurrence and metastasis. There are no adequate clinical trials that define the optimal approach to patients with metastatic salivary gland tumors due to its rarity. Systemic therapy is reserved for cases where local therapy, such as radiation or metastasectomy, is not appropriate. Nevertheless, there is insufficient data in the literature regarding the chemotherapy of choice for metastatic ACC. In this article, we report a case of metastatic ACC of the right parotid gland that progressed on carboplatin and paclitaxel after partial response followed by doxorubicin and is currently on checkpoint inhibitor treatment.

  18. Pulmonary Tumor Thrombotic Microangiopathy Caused by a Parotid Tumor: Early Antemortem Diagnosis and Long-term Survival

    PubMed Central

    Toyonaga, Haruka; Tsuchiya, Michiko; Sakaguchi, Chikara; Ajimizu, Hitomi; Nakanishi, Yosuke; Nishiyama, Seiya; Morikawa, Noboru; Hayashi, Yasuyuki; Nagasaka, Yukio; Yasui, Hiroshi

    2017-01-01

    Pulmonary tumor thrombotic microangiopathy (PTTM) is a high-mortality disease that is difficult to diagnose clinically. Our patient was an 80-year-old woman who came to us due to symptoms of increasing dyspnea. A clinical evaluation showed that she had hypoxemia and pulmonary arterial hypertension without any abnormalities in the major pulmonary arteries, bronchi, or alveoli. A lung perfusion scan showed multiple wedge-shaped perfusion defects. Further examination revealed adenocarcinoma in her right parotid gland with metastasis to the submandibular lymph nodes. We diagnosed her to have PTTM caused by a parotid tumor. The patient survived for 11 months with chemotherapy. An early antemortem diagnosis by minimally invasive examinations will help PTTM patients to survive longer. PMID:28050002

  19. Pancreatic Fat Accumulation, Fibrosis, and Acinar Cell Injury in the Zucker Diabetic Fatty Rat Fed a Chronic High-Fat Diet

    PubMed Central

    Matsuda, Akiko; Makino, Naohiko; Tozawa, Tomohiro; Shirahata, Nakao; Honda, Teiichiro; Ikeda, Yushi; Sato, Hideyuki; Ito, Miho; Kakizaki, Yasuharu; Akamatsu, Manabu; Ueno, Yoshiyuki; Kawata, Sumio

    2014-01-01

    Objective The histological alteration of the exocrine pancreas in obesity has not been clarified. In the present study, we investigated biochemical and histological changes in the exocrine pancreas of obese model rats. Methods Zucker lean rats were fed a standard diet, and Zucker diabetic fatty (ZDF) rats were divided into 2 groups fed a standard diet and a high-fat diet, respectively. These experimental groups were fed each of the diets from 6 weeks until 12, 18, 24 weeks of age. We performed blood biochemical assays and histological analysis of the pancreas. Results In the ZDF rats fed a high-fat diet, the ratio of accumulated pancreatic fat area relative to exocrine gland area was increased significantly at 18 weeks of age in comparison with the other 2 groups (P < 0.05), and lipid droplets were observed in acinar cells. Subsequently, at 24 weeks of age in this group, pancreatic fibrosis and the serum exocrine pancreatic enzyme levels were increased significantly relative to the other 2 groups (P < 0.01). Conclusions In ZDF rats fed a chronic high-fat diet, fat accumulates in pancreatic acinar cells, and this fatty change seems to be related to subsequent pancreatic fibrosis and acinar cell injury. PMID:24717823

  20. Metastatic pancreatic acinar cell carcinoma in a younger male with marked AFP production: A potential pitfall on fine needle aspiration biopsy.

    PubMed

    Valente, Kari; Yacoub, George; Cappellari, James O; Parks, Graham

    2017-02-01

    A 30-year-old male presented to his doctor with complaints of abdominal pain and was found to have retroperitoneal as well as multiple hepatic masses. A serum alpha-fetoprotein (AFP) level was significantly elevated (17,373 ng mL(-1) ), raising suspicions for a metastatic germ cell tumor. Fine needle aspiration biopsy of the pancreatic lesion revealed atypical epithelioid cells with round nuclei, large prominent nucleoli, and granular cytoplasm. The morphologic differential diagnosis included pancreatic neoplasm, metastatic germ cell tumor, other metastatic carcinoma, and melanoma. An extensive panel of immunohistochemical stains confirmed the diagnosis of acinar cell carcinoma. The diagnosis of acinar cell carcinoma could be confounded by the markedly increased AFP level, particularly in the setting of a retroperitoneal mass in a younger male. The increased AFP level in the setting of an acinar cell tumor is a potential pitfall to correct diagnosis by cytology. As the treatment for these two entities differs considerably, acute awareness of the phenomenon is important. We present a case of pancreatic ACC with an increased AFP level diagnosed on a cytology specimen. Diagn. Cytopathol. 2017;45:133-136. © 2016 Wiley Periodicals, Inc.

  1. SU-E-J-109: Evaluation of Deformable Accumulated Parotid Doses Using Different Registration Algorithms in Adaptive Head and Neck Radiotherapy

    SciTech Connect

    Xu, S; Liu, B

    2015-06-15

    Purpose: Three deformable image registration (DIR) algorithms are utilized to perform deformable dose accumulation for head and neck tomotherapy treatment, and the differences of the accumulated doses are evaluated. Methods: Daily MVCT data for 10 patients with pathologically proven nasopharyngeal cancers were analyzed. The data were acquired using tomotherapy (TomoTherapy, Accuray) at the PLA General Hospital. The prescription dose to the primary target was 70Gy in 33 fractions.Three DIR methods (B-spline, Diffeomorphic Demons and MIMvista) were used to propagate parotid structures from planning CTs to the daily CTs and accumulate fractionated dose on the planning CTs. The mean accumulated doses of parotids were quantitatively compared and the uncertainties of the propagated parotid contours were evaluated using Dice similarity index (DSI). Results: The planned mean dose of the ipsilateral parotids (32.42±3.13Gy) was slightly higher than those of the contralateral parotids (31.38±3.19Gy)in 10 patients. The difference between the accumulated mean doses of the ipsilateral parotids in the B-spline, Demons and MIMvista deformation algorithms (36.40±5.78Gy, 34.08±6.72Gy and 33.72±2.63Gy ) were statistically significant (B-spline vs Demons, P<0.0001, B-spline vs MIMvista, p =0.002). And The difference between those of the contralateral parotids in the B-spline, Demons and MIMvista deformation algorithms (34.08±4.82Gy, 32.42±4.80Gy and 33.92±4.65Gy ) were also significant (B-spline vs Demons, p =0.009, B-spline vs MIMvista, p =0.074). For the DSI analysis, the scores of B-spline, Demons and MIMvista DIRs were 0.90, 0.89 and 0.76. Conclusion: Shrinkage of parotid volumes results in the dose increase to the parotid glands in adaptive head and neck radiotherapy. The accumulated doses of parotids show significant difference using the different DIR algorithms between kVCT and MVCT. Therefore, the volume-based criterion (i.e. DSI) as a quantitative evaluation of

  2. Bilateral parotid enlargement due to malnutrition under the influence of the media in an adolescent in Lithuania.

    PubMed

    Mieliauskaite, Diana; Venalis, Algirdas; Graziene, Vida; Kirdaite, Gailute

    2007-07-01

    The elimination of censorship for the media in post-communist countries in transition has contributed to increases in the prevalence of several medical problems. Children and adolescents are particularly vulnerable to the messages conveyed through the media, which influence their perceptions and behaviour. We describe a case of bilateral parotid enlargement due to malnutrition under the influence of self-prescribed diet in an adolescent. A 15-year-old girl reported to our institution under suspicion of Sjögren's syndrome for medical advice. Two months ago she developed persistent bilateral parotid enlargement and a dry mouth. Her medical history revealed a weight loss due to "self-prescribed" reduce diet. Social questioning clarified high use of the media and influence on the body concept and self image. On extra oral examination, a diffuse parotid enlargement was seen bilaterally. The examination of the mouth showed a low moisture level of the intraoral mucosa. The unstimulated whole salivary flow rate was 2 ml in 15 min. Laboratory findings evidenced anemia (107 g/l). The serum albumin concentration indicated a reduced level (28 g/l). Search for antinuclear antibodies, anti-SSA antibodies, anti-SSB, -Sm, -RNP and anti-double-stranded DNA antibodies was negative. Evaluation for antibodies against hepatitis C, cytomegalovirus and Epstein-Barr virus infection and HIV rendered negative results. A histopathologic examination of labial salivary gland biopsy revealed a picture of sialoadenosis. From the above investigations, a diagnosis of sialoadenosis due to malnutrition was made.

  3. Effects of dietary consistency and water content on parotid amylase secretion and gastric starch digestion in rats.

    PubMed

    Kurahashi, M; Inomata, K

    1999-12-01

    The aim was to estimate the significance of oral sensation and mastication in inducing amylase secretion from the parotid gland and subsequent starch digestion in the stomach. Rats were fed three diets of similar chemical composition but different physical presentations. Two were solid, either pellets or powder, and one was liquid. Oral sensory activity would be greatest with the pellets and least with the liquid. Only the pellets would require significant mastication. Three criteria were used to estimate amylase secretion, amylase activity in the stomach, the depletion of glandular amylase activity and plasma amylase concentrations. Gastric starch digestion was estimated by measuring the concentration of reducing-sugars in the stomach contents. Parotid amylase secretion and gastric starch digestion were similar whether rats were fed pelleted or powdered solid food but much lower in rats fed a liquid diet. These findings support the view that it is the contact of dry food with the oral mucosa rather than the jaw movements involved in mastication that stimulates parotid amylase secretion.

  4. Immunosuppression abrogates resistance of young rabbits to Rabbit Haemorrhagic Disease (RHD).

    PubMed

    Marques, Raquel M; Teixeira, Luzia; Aguas, Artur P; Ribeiro, Joana C; Costa-e-Silva, António; Ferreira, Paula G

    2014-02-04

    Rabbit Haemorrhagic Disease (RHD) is caused by a calicivirus (RHDV) that kills 90% of infected adult European rabbits within 3 days. Remarkably, young rabbits are resistant to RHD. We induced immunosuppression in young rabbits by treatment with methylprednisolone acetate (MPA) and challenged the animals with RHDV by intramuscular injection. All of these young rabbits died within 3 days of infection due to fulminant hepatitis, presenting a large number of RHDV-positive dead or apoptotic hepatocytes, and a significant seric increase in cytokines, features that are similar to those of naïve adult rabbits infected by RHDV. We conclude that MPA-induced immunosuppression abrogates the resistance of young rabbits to RHD, indicating that there are differences in the innate immune system between young and adult rabbits that contribute to their distinct resistance/susceptibility to RHDV infection.

  5. No Effect of Dietary Aspartame or Stevia on Pancreatic Acinar Carcinoma Development, Growth, or Induced Mortality in a Murine Model

    PubMed Central

    Dooley, James; Lagou, Vasiliki; Dresselaers, Tom; van Dongen, Katinka A.; Himmelreich, Uwe; Liston, Adrian

    2017-01-01

    Pancreatic cancer has an extremely poor prognosis, largely due to a poor record for early detection. Known risk factors for pancreatic cancer include obesity, diet, and diabetes, implicating glucose consumption and regulation as a key player. The role of artificial sweeteners may therefore be pertinent to disease kinetics. The oncogenic impact of artificial sweeteners is a highly controversial area. Aspartame, one of the most studied food additives, is widely recognized as being generally safe, although there are still specific areas where research is incomplete due to study limitations. Stevia, by contrast, has been the subject of relatively few studies, and the potential health benefits are based on extrapolation rather than direct testing. Here, we used longitudinal tracking of pancreatic acinar carcinoma development, growth, and lethality in a sensitized mouse model. Despite exposure to aspartame and stevia from the in utero stage onward, we found no disease modification activity, in either direction. These results contribute to the data on aspartame and stevia safety, while also reducing confidence in several of the purported health benefits. PMID:28232906

  6. E-cadherin-negative acinar cell carcinoma of the pancreas: report of a case showing a solid pseudopapillary growth pattern.

    PubMed

    Tajima, Shogo; Waki, Michihiko; Azuma, Masaki; Koda, Kenji; Ohata, Akihiko

    2016-09-01

    E-cadherin expression patterns in acinar cell carcinomas (ACCs) of the pancreas have not been well documented. Herein, we present a hitherto undescribed case of E-cadherin-negative ACC with a solid pseudopapillary growth pattern in a 65-year-old man. We used an antibody against the extracellular domain of E-cadherin. As a further unusual status in ACC, faint β-catenin expression was observed in the cytoplasm of carcinoma cells. Morphological distinction from a solid pseudopapillary neoplasm (SPN) of the pancreas might be problematic in such a case, because of their similarities concerned with the growth pattern and E-cadherin negativity. Without nuclear accumulation of β-catenin, a diagnosis of SPN was almost excluded. Immunoreactivity for trypsin and BCL10 made an accurate diagnosis of ACC to this case. The tumor recurred 10 months post-surgery as rapidly enlarging masses in the liver, presumably indicating the aggressiveness of the E-cadherin-negative phenotype among ACCs.

  7. Long-term persistence and development of induced pancreatic beta cells generated by lineage conversion of acinar cells.

    PubMed

    Li, Weida; Cavelti-Weder, Claudia; Zhang, Yingying; Zhang, Yinying; Clement, Kendell; Donovan, Scott; Gonzalez, Gabriel; Zhu, Jiang; Stemann, Marianne; Xu, Ke; Hashimoto, Tatsu; Yamada, Takatsugu; Nakanishi, Mio; Zhang, Yuemei; Zeng, Samuel; Gifford, David; Meissner, Alexander; Weir, Gordon; Zhou, Qiao

    2014-12-01

    Direct lineage conversion is a promising approach to generate therapeutically important cell types for disease modeling and tissue repair. However, the survival and function of lineage-reprogrammed cells in vivo over the long term has not been examined. Here, using an improved method for in vivo conversion of adult mouse pancreatic acinar cells toward beta cells, we show that induced beta cells persist for up to 13 months (the length of the experiment), form pancreatic islet-like structures and support normoglycemia in diabetic mice. Detailed molecular analyses of induced beta cells over 7 months reveal that global DNA methylation changes occur within 10 d, whereas the transcriptional network evolves over 2 months to resemble that of endogenous beta cells and remains stable thereafter. Progressive gain of beta-cell function occurs over 7 months, as measured by glucose-regulated insulin release and suppression of hyperglycemia. These studies demonstrate that lineage-reprogrammed cells persist for >1 year and undergo epigenetic, transcriptional, anatomical and functional development toward a beta-cell phenotype.

  8. TP53 alterations in pancreatic acinar cell carcinoma: new insights into the molecular pathology of this rare cancer.

    PubMed

    La Rosa, Stefano; Bernasconi, Barbara; Frattini, Milo; Tibiletti, Maria Grazia; Molinari, Francesca; Furlan, Daniela; Sahnane, Nora; Vanoli, Alessandro; Albarello, Luca; Zhang, Lizhi; Notohara, Kenji; Casnedi, Selenia; Chenard, Marie-Pierre; Adsay, Volkan; Asioli, Sofia; Capella, Carlo; Sessa, Fausto

    2016-03-01

    The molecular alterations of pancreatic acinar cell carcinomas (ACCs) are poorly understood and have been reported as being different from those in ductal adenocarcinomas. Loss of TP53 gene function in the pathogenesis of ACCs is controversial since contradictory findings have been published. A comprehensive analysis of the different possible genetic and epigenetic mechanisms leading to TP53 alteration in ACC has never been reported and hence the role of TP53 in the pathogenesis and/or progression of ACC remains unclear. We investigated TP53 alterations in 54 tumor samples from 44 patients, including primary and metastatic ACC, using sequencing analysis, methylation-specific multiplex ligation probe amplification, fluorescence in situ hybridization, and immunohistochemistry. TP53 mutations were found in 13 % of primary ACCs and in 31 % of metastases. Primary ACCs and metastases showed the same mutational profile, with the exception of one case, characterized by a wild-type sequence in the primary carcinoma and a mutation in the corresponding metastasis. FISH analysis revealed deletion of the TP53 region in 53 % of primary ACCs and in 50 % of metastases. Promoter hypermethylation was found in one case. The molecular alterations correlated well with the immunohistochemical findings. A statistically significant association was found between the combination of mutation of one allele and loss of the other allele of TP53 and worse survival.

  9. Ultrasonic Nakagami-parameter characterization of parotid-gland injury following head-and-neck radiotherapy: A feasibility study of late toxicity

    SciTech Connect

    Yang, Xiaofeng; Wu, Ning; Wang, Yuefeng; Tridandapani, Srini; Beitler, Jonathan J.; Yu, David S.; Curran, Walter J.; Liu, Tian; Bruner, Deborah W.

    2014-02-15

    Purpose: The study aims to investigate whether Nakagami parameters—estimated from the statistical distribution of the backscattered ultrasound radio-frequency (RF) signals—could provide a means for quantitative characterization of parotid-gland injury resulting from head-and-neck radiotherapy. Methods: A preliminary clinical study was conducted with 12 postradiotherapy patients and 12 healthy volunteers. Each participant underwent one ultrasound study in which ultrasound scans were performed in the longitudinal, i.e., vertical orientation on the bilateral parotids. For the 12 patients, the mean radiation dose to the parotid glands was 37.7 ± 9.5 Gy, and the mean follow-up time was 16.3 ± 4.8 months. All enrolled patients experienced grade 1 or 2 late salivary-gland toxicity (RTOG/EORTC morbidity scale). The normal parotid glands served as the control group. The Nakagami-scaling and Nakagami-shape parameters were computed from the RF data to quantify radiation-induced parotid-gland changes. Results: Significant differences in Nakagami parameters were observed between the normal and postradiotherapy parotid glands. Compared with the control group, the Nakagami-scaling parameter of the postradiotherapy group decreased by 25.8% (p < 0.001), and the Nakagami-shape parameter decreased by 31.3% (p < 0.001). The area under the receiver operating characteristic curve was 0.85 for the Nakagami-scaling parameter and was 0.95 for the Nakagami-shape parameter, which further demonstrated the diagnostic efficiency of the Nakagami parameters. Conclusions: Nakagami parameters could be used to quantitatively measure parotid-gland injury following head-and-neck radiotherapy. Moreover, the clinical feasibility was demonstrated and this study provides meaningful preliminary data for future clinical investigation.

  10. Dosimetric consequences of the parotid glands using CT-to-CBCT deformable registration during IMRT for late stage head and neck cancers

    NASA Astrophysics Data System (ADS)

    Conill, Annette L.

    Patients receiving Intensity Modulated Radiation Therapy (IMRT) for late stage head and neck (HN) cancer often experience anatomical changes due to weight loss, tumor regression, and positional changes of normal anatomy (1). As a result, the actual dose delivered may vary from the original treatment plan. The purpose of this study was (a) to evaluate the dosimetric consequences of the parotid glands during the course of treatment, and (b) to determine if there would be an optimal timeframe for replanning. Nineteen locally advanced HN cancer patients underwent definitive IMRT. Each patient received an initial computerized tomography simulation (CT-SIM) scan and weekly cone beam computerized tomography (CBCT) scans. A Deformable Image Registration (DIR) was performed between the CT-SIM and CBCT of the parotid glands and Planning Target Volumes (PTVs) using the Eclipse treatment planning system (TPS) and the Velocity deformation software. A recalculation of the dose was performed on the weekly CBCTs using the original monitor units. The parameters for evaluation of our method were: the changes in volume of the PTVs and parotid glands, the dose coverage of the PTVs, the lateral displacement in the Center of Mass (COM), the mean dose, and Normal Tissue Complication Probability (NTCP) of the parotid glands. The studies showed a reduction of the volume in the PTVs and parotids, a medial displacement in COM, and alterations of the mean dose to the parotid glands as compared to the initial plans. Differences were observed for the dose volume coverage of the PTVs and NTCP of the parotid gland values between the initial plan and our proposed method utilizing deformable registration-based dose calculations.

  11. The Rabbit Corneal Pocket Assay.

    PubMed

    Morbidelli, Lucia; Ziche, Marina

    2016-01-01

    The rabbit corneal micropocket angiogenesis assay uses the avascular cornea as a substrate canvas to study angiogenesis in vivo. Through the use of standardized slow-release pellets, a predictable angiogenic response is generated over the course of 1-2 weeks and then quantified. Uniform slow-release pellets are prepared by mixing purified angiogenic growth factors such as basic fibroblast growth factor or vascular endothelial growth factor and a synthetic polymer to allow slow release. A micropocket is surgically created in the rabbit cornea under anesthesia and a pellet implanted. On the days later, the angiogenic response is measured and qualified using a slit lamp, as well as the concomitant vascular phenotype or inflammatory features. The results of the assay are used to assess the ability of potential therapeutic molecules to modulate angiogenesis in vivo, both when released locally or given by ocular formulations or through systemic treatment. In this chapter, the experimental details of the rabbit cornea assay and technical implementations to the original protocol are described.

  12. FDG-PET Assessment of the Effect of Head and Neck Radiotherapy on Parotid Gland Glucose Metabolism

    SciTech Connect

    Roach, Michael C.; Turkington, Timothy G.; Higgins, Kristin A.; Hawk, Thomas C.; Hoang, Jenny K.; Brizel, David M.

    2012-01-01

    Purpose: Functional imaging with [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) provides the opportunity to define the physiology of the major salivary glands before and after radiation therapy. The goal of this retrospective study was to identify the radiation dose-response relationship of parotid gland glucose metabolism in patients with head and neck squamous cell carcinoma (HNSCC). Materials and Methods: Forty-nine adults with HNSCC were identified who had curative intent intensity-modulated radiation therapy (IMRT) and FDG-PET imaging before and after treatment. Using a graphical user interface, contours were delineated for the parotid glands on axial CT slices while all authors were blinded to paired PET slices. Average and maximal standard uptake values (SUV) were measured within these anatomic regions. Changes in SUV and volume after radiation therapy were correlated with parotid gland dose-volume histograms from IMRT plans. Results: The average parotid gland volume was 30.7 mL and contracted 3.9 {+-} 1.9% with every increase of 10 Gy in mean dose (p = 0.04). However, within the first 3 months after treatment, there was a uniform reduction of 16.5% {+-} 7.3% regardless of dose. The average SUV{sub mean} of the glands was 1.63 {+-} 0.48 pretreatment and declined by 5.2% {+-} 2.5% for every increase of 10 Gy in mean dose (p = 0.04). The average SUV{sub max} was 4.07 {+-} 2.85 pretreatment and decreased in a sigmoid manner with mean dose. A threshold of 32 Gy for mean dose existed, after which SUV{sub max} declined rapidly. Conclusion: Radiation dose responses of the parotid glands can be measured by integrated CT/FDG-PET scans. Retrospective analysis showed sigmoidal declines in the maximum metabolism but linear declines in the average metabolism of the glands with dose. Future studies should correlate this decline in FDG uptake with saliva production to improve treatment planning.

  13. Efficacy of Transcutaneous Electric Nerve Stimulation on Parotid Saliva Flow Rate in Relation to Age and Gender

    PubMed Central

    Dhillon, Manu; M Raju, Srinivasa; S Mohan, Raviprakash; Tomar, Divya

    2016-01-01

    Statement of the Problem Treatment with salivary substitutes and stimulation of salivary flow by either mechanical or pharmacologic methods has side effects and only provides symptomatic relief but no long-lasting results. Purpose To assess the effectiveness of extraoral transcutaneous electric nerve stimulation (TENS) as a mean of stimulating salivary function in healthy adult subjects; as well as to determine the gender and age-dependent changes in salivary flow rates of unstimulated and stimulated parotid saliva. Materials and Method Hundred patients were divided into two groups; Group I aged 20-40 and Group II aged ≥ 60 years. The TENS electrode pads were externally placed on the skin overlying the parotid glands. Unstimulated and stimulated parotid saliva was collected for 5 minutes each by using standardized collection techniques. Results Eighty seven of 100 subjects demonstrated increased salivary flow when stimulated via the TENS unit. Ten experienced no increase and 3 experienced a decrease. The mean unstimulated salivary flow rate was 0.01872 ml/min in Group I and 0.0088 ml/min in Group II. The mean stimulated salivary flow rate was 0.03084 ml/min (SD= 0.01248) in Group I, and 0.01556 ml/min (SD 0.0101) in Group II. After stimulation, the amount of salivary flow increased significantly in both groups (p< 0.001). Statistical comparison of the two groups revealed them to be significantly different (p< 0.001), with Group I producing more saliva. Gender-wise, no statistically significant difference was seen among the subjects in Group I (p = 0.148), and those in Group II (p= 0.448). Out of 12 subjects with 0 baseline flows, 7 continued to have no flow. Five subjects observed side effects, although minimal and transient. Conclusion The TENS unit was effective in increasing parotid gland salivary flow in healthy subjects. There was age-related but no gender-related variability in parotid salivary flow rate. PMID:27602390

  14. Sodium tungstate on some biochemical parameters of the parotid salivary gland of streptozotocin-induced diabetic rats: a short-term study.

    PubMed

    Leite, Mariana Ferreira; Nicolau, José

    2009-02-01

    Several studies have shown the antidiabetic properties of sodium tungstate. In this study, we evaluated some biochemical parameters of the parotid salivary gland of streptozotocin-induced diabetic rats treated with sodium tungstate solution (2 mg/ml). The studied groups were: untreated control (UC), treated control (TC), untreated diabetic (UD), and treated diabetic (TD). After 2 and 6 weeks of treatment, parotid gland was removed and total protein and sialic acid (free and total) concentration and amylase and peroxidase activities were determined. Data were compared by variance analysis and Tukey test (p < 0.05). The sodium tungstate treatment modestly decreased the glycemia of streptozotocin-induced diabetic rats. At week 2 of the study, parotid gland of diabetic rats presented a reduction of total protein concentration (55%) and an increase of amylase (120%) and peroxidase (160%) activities, free (150%) and total (170%) sialic acid concentration. No alteration in the evaluated parameters at week 6 of the study was observed. Sodium tungstate presented no significant effect in parotid gland. Our results suggest that diabetes causes initial modification in biochemical composition of parotid. However, this gland showed a recovery capacity after 6 week of the experimental time. Sodium tungstate has no effect in peripheral tissues, such as salivary glands.

  15. Histological and histochemical study of the protective role of rosemary extract against harmful effect of cell phone electromagnetic radiation on the parotid glands.

    PubMed

    Ghoneim, Fatma M; Arafat, Eetmad A

    2016-06-01

    Electromagnetic fields (EMFs) are a class of non-ionizing radiation (NIR) that is emitted from mobile phone. It may have hazardous effects on parotid glands. So, we aimed to investigate the histological and histochemical changes of the parotid glands of rats exposed to mobile phone and study the possible protective role of rosemary against its harmful effect. Forty adult male albino rats were used in this study. They were classified into 4 equal groups. Group I (control), group II (control receiving rosemary), group III (mobile phone exposed group) and group IV (mobile exposed, rosemary treated group). Parotid glands were dissected out for histological and histochemical study. Moreover, measurement of oxidative stress markers; malondialdehyde (MDA) and total antioxidant capacity (TAC) was done. The results of this study revealed that rosemary has protective effect through improving the histological and histochemical picture of the parotid gland in addition of its antioxidant effect. It could be concluded from the current study, that exposure of parotid gland of rat models to electromagnetic radiation of mobile phone resulted in structural changes at the level of light and electron microscopic examination which could be explained by oxidative stress effect of mobile phone. Rosemary could play a protective role against this harmful effect through its antioxidant activity.

  16. Hormone-induced protein phosphorylation. I. Relationship between secretagogue action and endogenous protein phosphorylation in intact cells from the exocrine pancreas and parotid

    PubMed Central

    1982-01-01

    We undertook studies to determine whether secretagogue action on the exocrine pancreas and parotid is accompanied by phosphorylation of proteins in intact cells. For this purpose, rat pancreatic, and parotid lobules were preincubated with 32Pi for 45 min at 37 degrees C, washed, and then incubated at 37 degrees C in the presence or absence of secretagogues that effect discharge through different second messengers. Among a variety of polypeptides exhibiting enhanced phosphorylation in pancreatic lobules upon a 30-s incubation in the presence of the secretagogues carbamylcholine, cholecystokinin octapeptide, or secretin, one species with an Mr of 29,000 was especially notable for three reasons: (a) its enhanced level of phosphorylation was dependent on the dose of secretagogue used and was still apparent after incubation for 30 min at 37 degrees C; (b) an analogous phosphorylated polypeptide was observed in isoproterenol- stimulated parotid lobules; and (c) in both tissues its selective dephosphorylation was observed upon termination of stimulation by administration of atropine to carbamylcholine-stimulated pancreatic lobules and propranolol to isoproterenol-stimulated parotid lobules. These results suggest that the phosphorylation of one protein with an Mr of 29,000 is closely correlated both temporally and in a dose- dependent fashion with secretagogue action in both the exocrine pancreas and parotid. PMID:6296160

  17. Prognostic value of proliferating cell nuclear antigen in parotid gland cancer.

    PubMed

    Stenner, Markus; Demgensky, Ariane; Molls, Christoph; Hardt, Aline; Luers, Jan C; Grosheva, Maria; Huebbers, Christian U; Klussmann, Jens P

    2012-04-01

    Although cell proliferation is related to tumour aggressiveness and prognosis, there are few studies describing the expression of proliferative markers in salivary gland cancer. Our aim was to assess the long-term prognostic value of the proliferating cell nuclear antigen (PCNA) in a large group of histologically different salivary gland cancers. We analysed the expression of PCNA in 159 patients with parotid gland cancer by means of immunohistochemistry. The mean follow-up time was 56.6 months. A high expression of PCNA showed a significant correlation to the patients' pathological lymph node stage (p = 0.004). A high PCNA expression significantly indicated a poor 5-year disease-free (p = 0.046) and overall survival rate (p = 0.018). The PCNA expression was the only prognostic factor for a worse 5-year disease-free and overall survival in acinic cell carcinomas (p = 0.004, p = 0.022). The correlation between PCNA expression and survival probabilities of salivary gland cancer might make proliferation markers helpful tools in patient follow-up, prognosis and targeted therapy in salivary gland cancer in future.

  18. The effect of oral stimulation on human parotid salivary flow rate and alpha-amylase secretion.

    PubMed

    Froehlich, D A; Pangborn, R M; Whitaker, J R

    1987-01-01

    Unilateral parotid saliva was collected from ten subjects following oral stimulation with water as baseline, and aqueous solutions of starch (2.5, 5.0, and 10%), sucrose (0.1, 0.2, and 0.4 M) sodium chloride (0.075, 0.15, and 0.30 M), and citric acid (0.005, 0.01, and 0.02 M). Salivary flow rate increased with increasing levels of each taste stimulus. At concentrations of equal taste intensity, citric acid evoked the highest flow rate, followed by sodium chloride and sucrose, while starch, in solution, had a minimal effect. Secretion rate patterns for total protein and alpha-amylase mirrored those of flow rate. The total protein and alpha-amylase concentrations of the saliva, and specific activity of alpha-amylase, were influenced by the type but not the concentration of stimulus, with citric acid stimulation resulting in the lowest concentrations and highest specific activity. Sodium ion (Na+) concentration generally increased with increasing stimulated flow rate, while K+, Ca++, and Mg++ concentrations remained relatively constant. Subjects with lower flow rates had a more concentrated saliva than those with high flow, except for Na+ concentration. Oral stimulation resulted in similar changes in protein and alpha-amylase secretion rates for the two groups.

  19. A safe transoral surgical approach to parapharyngeal tumor arising from deep lobe of parotid gland

    PubMed Central

    Casale, Manuele; Capuano, Francesco; Sabatino, Lorenzo; Pace, Annalisa; Oliveto, Giuseppe; Vella, Paola; Moffa, Antonio; Salvinelli, Fabrizio

    2016-01-01

    The management of parapharyngeal tumor is surgical, but the approach remains a challenge. Attention should be paid to avoidance intra-operative bleeding or cranial nerves damage. We report a case of a 67-year-old male complaining of left-ear fullness. A submucosal mass arising from the lateral wall of oropharynx on the left side was observed. Magnetic resonance imaging detected a mass arising from the parotid gland, in particular from the deep lobe, and a fine needle biopsy was compatible with “Warthin tumor.” We performed a mini-invasive transoral approach under magnification, previous isolation of homolateral vessels. The decision on which surgical approach to be used is determined by site, size vascularity, and histology of the tumor. A literature review of the main surgical approaches was performed. We performed a combined transoral dissection under magnification with cervicotomic exposure of the neck vascular bundle allowing to dissect the tumor and manage any intra-operative complications. PMID:28228953

  20. A pediatric case of mammary analogue secretory carcinoma within the parotid.

    PubMed

    Quattlebaum, S Craig; Roby, Brianne; Dishop, Megan K; Said, M Sherif; Chan, Kenny

    2015-01-01

    Mammary analogue secretory carcinoma (MASC) is a recently described entity in the differential diagnosis of salivary gland tumors. It is notable for a characteristic t(12;15)(p13;q25) translocation that results in a unique fusion protein, ETV6-NTRK3. While several studies have retrospectively identified this translocation in cases previously diagnosed as a different salivary malignancy, there have been relatively few cases where this translocation was identified on initial pathology results, and fewer still in a pediatric population. We present a case of a 15 year old female with a slowly enlarging, painless, left facial mass. MRI demonstrated a cystic mass extending into the deep lobe of the parotid, and she underwent parotidectomy. The tumor cells stained positive for S100 and CK19. ETV6 translocation was present, confirming the diagnosis. Mammary analogue secretory carcinoma is a recently described tumor of the salivary glands, which often masquerades as more common primary salivary gland tumors and cysts. More research is needed to characterize the typical behavior of this neoplasm and the optimal treatment regimen. With identification of its characteristic translocation, mammary analogue secretory carcinoma can be easily differentiated from its more prevalent counterparts, and should therefore remain within the differential of the pathologist and head and neck surgeon.

  1. Elective neck management for squamous cell carcinoma metastatic to the parotid area lymph nodes.

    PubMed

    Herman, Michael P; Amdur, Robert J; Werning, John W; Dziegielewski, Peter; Morris, Christopher G; Mendenhall, William M

    2016-11-01

    The objective of this study is to determine if radiotherapy (RT) alone to the cervical lymphatics is a suitable alternative to elective neck dissection (END) in patients who undergo parotidectomy and postoperative RT for squamous cell carcinoma metastatic to the parotid area lymph nodes (PALN). We retrospectively reviewed the medical records of 107 patients consecutively treated from November 1969 to March 2012 for cutaneous squamous cell carcinoma metastatic to the PALN with a clinically node-negative neck. Primary therapy consisted of parotidectomy in all cases. We compared regional (cervical) control in two subgroups: 42 patients treated with END and RT and 65 patients treated with elective neck irradiation (ENI) alone. The median time of follow-up was 5.5 years (range 0.3-30 years) for all patients and 11 years for living patients (range 1.8-26 years). There was 1 neck recurrence in each subgroup: END and RT, 1/42 (2 %); and ENI alone, 1/65 (1.5 %). No patient experienced a complication related to neck RT. ENI to a dose of approximately 50-60 Gy is a suitable alternative to END and postoperative RT in patients with squamous cell carcinoma metastatic to the PALN.

  2. Purification and characterization of a high-Mr carbonic anhydrase from sheep parotid gland.

    PubMed Central

    Fernley, R T; Coghlan, J P; Wright, R D

    1988-01-01

    Approximately half the carbonic anhydrase activity of sheep parotid-gland homogenate is derived from a high-Mr protein [Fernley, Wright & Coghlan (1979) FEBS Lett. 105, 299-302]. This enzyme has now been purified to homogeneity, and its properties were compared with those of the well-characterized sheep carbonic anhydrase II. The protein has an apparent Mr of 540,000 as measured by gel filtration under non-denaturing conditions and an apparent subunit Mr of 45,000 as measured by SDS/polyacrylamide-gel electrophoresis. After deglycosylation with the enzyme N-glycanase the protein migrates with an apparent Mr of 36,000 on SDS/polyacrylamide-gel electrophoresis. The CO2-hydrating activity was 340 units/mg compared with 488 units/mg for sheep carbonic anhydrase II measured under identical conditions. This enzyme does not, however, hydrolyse p-nitrophenyl acetate. The enzyme contains 0.8 g-atom of zinc/mol of protein subunit. The peptide maps of the two carbonic anhydrases differ significantly from one another, indicating they are not related closely structurally. Unlike the carbonic anhydrase II isoenzyme, which has a blocked N-terminus, the high-Mr enzyme has a free glycine residue at its N-terminus. Images Fig. 4. Fig. 6. Fig. 7. PMID:3124821

  3. Single Cell Clones Purified from Human Parotid Glands Display Features of Multipotent Epitheliomesenchymal Stem Cells

    PubMed Central

    Yi, TacGhee; Lee, Songyi; Choi, Nahyun; Shin, Hyun-Soo; Kim, Junghee; Lim, Jae-Yol

    2016-01-01

    A better understanding of the biology of tissue-resident stem cell populations is essential to development of therapeutic strategies for regeneration of damaged tissue. Here, we describe the isolation of glandular stem cells (GSCs) from a small biopsy specimen from human parotid glands. Single colony-forming unit-derived clonal cells were isolated through a modified subfractionation culture method, and their stem cell properties were examined. The isolated clonal cells exhibited both epithelial and mesenchymal stem cell (MSC)-like features, including differentiation potential and marker expression. The cells transiently displayed salivary progenitor phenotypes during salivary epithelial differentiation, suggesting that they may be putative multipotent GSCs rather than progenitor cells. Both epithelial and mesenchymal-expressing putative GSCs, LGR5+CD90+ cells, were found in vivo, mostly in inter-secretory units of human salivary glands. Following in vivo transplantation into irradiated salivary glands of mice, these cells were found to be engrafted around the secretory complexes, where they contributed to restoration of radiation-induced salivary hypofunction. These results showed that multipotent epitheliomesenchymal GSCs are present in glandular mesenchyme, and that isolation of homogenous GSC clones from human salivary glands may promote the precise understanding of biological function of bona fide GSCs, enabling their therapeutic application for salivary gland regeneration. PMID:27824146

  4. Dopamine actions in vitro on enzyme and electrolyte secretion from normal and sympathectomized rat parotid glands.

    PubMed Central

    Danielsson, A; Henriksson, R; Sundström, S; Wester, P

    1988-01-01

    1. Adult rats were denervated unilaterally by removal of the left superior cervical ganglion or chemically denervated with 6-hydroxydopamine or reserpine. Two weeks later the parotid glands were used for in vitro secretory studies and their catecholamines and major metabolites were measured. 2. Noradrenaline concentrations were reduced 2 weeks after surgical sympathectomy and reserpine pre-treatment 18 h previously, whereas 6-hydroxydopamine pre-treatment for 3 days reduced both noradrenaline and dopamine concentrations. 3. Dopamine caused a prominent amylase release from incubated control glands. However, a subsensitivity for dopamine-induced amylase release was recorded on the denervated side. 4. Dopamine caused a prominent potassium efflux measured as 86Rb+ efflux from control glands, but was without effect in denervated glands. This is in contrast to noradrenaline-induced 86Rb+ efflux which was equally effective in both denervated and control glands. 5. Dopamine caused [3H]noradrenaline efflux in control glands, but was without effect in surgically denervated glands and in glands pre-treated with reserpine or 6-hydroxydopamine. 6. It is concluded that dopamine-induced potassium release is caused by a presynaptic action on noradrenergic nerves, whereas dopamine-induced amylase release has a presynaptic and a postsynaptic component. The results suggest a specific action of dopamine in salivary glands, with different effects on enzyme release and ionic fluxes. PMID:2473198

  5. Structural characterisation of parotid and whole mouth salivary pellicles adsorbed onto DPI and QCMD hydroxyapatite sensors.

    PubMed

    Ash, Anthony; Burnett, Gary R; Parker, Roger; Ridout, Mike J; Rigby, Neil M; Wilde, Peter J

    2014-04-01

    In this study we investigated the differences in the properties of pellicles formed from stimulated parotid saliva (PS), which contains little or no mucin; and stimulated whole mouth saliva (WMS), which contains mainly two types of mucin: MUC5B and MUC7. By contacting WMS and PS with quartz-crystal microbalance with dissipation monitoring (QCM-D) and dual polarisation interferometer (DPI) hydroxyapatite (the main component of enamel) coated sensors, we observed the formation and structure of the respective salivary pellicles. As this was the first time that DPI hydroxyapatite sensors have been used to measure salivary pellicle adsorption; the techniques combined allowed us to measure the hydrated mass, dry mass, thickness and viscoelastic properties of the pellicle; but also to record the density of the PS and WMS formed pellicles. Subsequently, the PS pellicle was shown to form a denser layer than WMS pellicle; which would suggest that the proteins present in PS are also responsible for forming the dense basal layer of the acquired enamel pellicle. Whereas proteins present in the WMS are more likely to help form the softer outer layer of the pellicle. The data presented help to further define the mechanisms leading to the multi-layered structure of the salivary pellicle and demonstrate that salivary composition has an important effect on the structural properties of the adsorbed pellicle.

  6. Ionizing irradiation induces apoptotic damage of salivary gland acinar cells via NADPH oxidase 1-dependent superoxide generation

    SciTech Connect

    Tateishi, Yoshihisa Sasabe, Eri; Ueta, Eisaku; Yamamoto, Tetsuya

    2008-02-08

    Reactive oxygen species (ROS) have important roles in various physiological processes. Recently, several novel homologues of the phagocytic NADPH oxidase have been discovered and this protein family is now designated as the Nox family. We investigated the involvement of Nox family proteins in ionizing irradiation-induced ROS generation and impairment in immortalized salivary gland acinar cells (NS-SV-AC), which are radiosensitive, and immortalized ductal cells (NS-SV-DC), which are radioresistant. Nox1-mRNA was upregulated by {gamma}-ray irradiation in NS-SV-AC, and the ROS level in NS-SV-AC was increased to approximately threefold of the control level after 10 Gy irradiation. The increase of ROS level in NS-SV-AC was suppressed by Nox1-siRNA-transfection. In parallel with the suppression of ROS generation and Nox1-mRNA expression by Nox1-siRNA, ionizing irradiation-induced apoptosis was strongly decreased in Nox1-siRNA-transfected NS-SV-AC. There were no large differences in total SOD or catalase activities between NS-SV-AC and NS-SV-DC although the post-irradiation ROS level in NS-SV-AC was higher than that in NS-SV-DC. In conclusion, these results indicate that Nox1 plays a crucial role in irradiation-induced ROS generation and ROS-associated impairment of salivary gland cells and that Nox1 gene may be targeted for preservation of the salivary gland function from radiation-induced impairment.

  7. Chronic Nicotine Exposure In Vivo and In Vitro Inhibits Vitamin B1 (Thiamin) Uptake by Pancreatic Acinar Cells.

    PubMed

    Srinivasan, Padmanabhan; Thrower, Edwin C; Loganathan, Gopalakrishnan; Balamurugan, A N; Subramanian, Veedamali S; Gorelick, Fred S; Said, Hamid M

    2015-01-01

    Thiamin (vitamin B1), a member of the water-soluble family of vitamins, is essential for normal cellular functions; its deficiency results in oxidative stress and mitochondrial dysfunction. Pancreatic acinar cells (PAC) obtain thiamin from the circulation using a specific carrier-mediated process mediated by both thiamin transporters -1 and -2 (THTR-1 and THTR-2; encoded by the SLC19A2 and SLC19A3 genes, respectively). The aim of the current study was to examine the effect of chronic exposure of mouse PAC in vivo and human PAC in vitro to nicotine (a major component of cigarette smoke that has been implicated in pancreatic diseases) on thiamin uptake and to delineate the mechanism involved. The results showed that chronic exposure of mice to nicotine significantly inhibits thiamin uptake in murine PAC, and that this inhibition is associated with a marked decrease in expression of THTR-1 and THTR-2 at the protein, mRNA and hnRNAs level. Furthermore, expression of the important thiamin-metabolizing enzyme, thiamin pyrophosphokinase (TPKase), was significantly reduced in PAC of mice exposed to nicotine. Similarly, chronic exposure of cultured human PAC to nicotine (0.5 μM, 48 h) significantly inhibited thiamin uptake, which was also associated with a decrease in expression of THTR-1 and THTR-2 proteins and mRNAs. This study demonstrates that chronic exposure of PAC to nicotine impairs the physiology and the molecular biology of the thiamin uptake process. Furthermore, the study suggests that the effect is, in part, mediated through transcriptional mechanism(s) affecting the SLC19A2 and SLC19A3 genes.

  8. IMMUNIZATION OF RABBITS TO INFECTIOUS PAPILLOMATOSIS

    PubMed Central

    Shope, Richard E.

    1937-01-01

    Two intraperitoneal injections of either infectious or non-infectious rabbit papilloma suspensions actively immunize rabbits against papillomatosis. The capacity of the non-infectious suspensions to immunize is considered as evidence that they contain papilloma virus even though none can be demonstrated by the usual infection test. PMID:19870596

  9. Mapping superficial lymphatic territories in the rabbit.

    PubMed

    Soto-Miranda, Miguel A; Suami, Hiroo; Chang, David W

    2013-06-01

    Little is known about the anatomy of the lymphatic system in the rabbit with regard to relationships between the lymphatic vessel and lymph node. According to our previous studies in human cadavers and canines, the superficial lymphatic system could be divided into lymphatic territories. The aim of this study was to completely map the superficial lymphatic system in the rabbit. We used our microinjection technique and histological analysis for dissecting studies and recently developed indocyanine green (ICG) fluorescent lymphography for demonstrating dynamic lymph flow in living rabbits. Real-time ICG fluorescent lymphography was performed in two living New Zealand White rabbits, and direct dye microinjection of the lymphatic vessels was performed in eight dead rabbits. To assess the relationships between the vascular and lymphatic systems in rabbits, we performed radiocontrast injection into arteries in two dead rabbits prior to the lymphatic injection. The ICG fluorescent lymphography revealed eight lymphatic territories in the preauricular, submandibular, root of the lateral neck, axillary, lumbar, inguinal, root of the tail, and popliteal regions. We injected blue acrylic dye into every lymphatic vessel 0.1 mm in diameter or larger. We then dissected and chased the stained lymphatic vessels proximally until the vessels connected to the first tier lymph node. This procedure was repeated throughout the body until all the relationships between the lymphatic vessels and lymph nodes were defined. The lymphatic system of the rabbit could be defined as eight lymphatic territories, each with its own lymphatic vessels and lymph node.

  10. Thermal cataract formation in rabbits

    SciTech Connect

    Kramar, P.; Harris, C.; Guy, A.W.

    1987-01-01

    Intraocularly circulating hot water was used to produce cataracts in nine eyes of seven rabbits by maintaining their retrolental temperatures between 43 degrees C and 45 degrees C. A rapid rate of heating (1.3 degrees C/min) plus a sharp temperature gradient across the eye may have been contributing factors in the consistent production of cataracts at these temperatures. Biomicroscopy and light microscopy showed lens changes similar to those associated with acute exposure to microwave radiation. These findings support the assumption that microwave cataractogenesis is due to the local production of elevated temperatures.

  11. Novel Calicivirus Identified in Rabbits, Michigan, USA

    PubMed Central

    Wise, Annabel G.; Bolin, Steven R.; Mullaney, Thomas P.; Kiupel, Matti; Maes, Roger K.

    2009-01-01

    We report a disease outbreak in a Michigan rabbitry of a rabbit calicivirus distinct from the foreign animal disease agent, rabbit hemorrhagic disease virus (RHDV). The novel virus has been designated Michigan rabbit calicivirus (MRCV). Caliciviruses of the Lagovirus genus other than RHDV have not been described in US rabbit populations. The case-fatality rate was 32.5% (65/200). Clinical signs included hemorrhage and sudden death, with hepatic necrosis. Analysis of viral RNA sequence from >95% of the viral genome showed an average similarity of 79% with RHDV. Similarity of the predicted MRCV capsid amino acid sequence ranged from 89.8% to 91.3%, much lower than the 98% amino acid similarity between RHDV strains. Experimentally infected rabbits lacked clinical disease, but MRCV was detected in tissues by PCR. We propose that MRCV primarily causes subclinical infection but may induce overt RHD-like disease under certain field conditions. PMID:19961675

  12. PKCθ activation in pancreatic acinar cells by gastrointestinal hormones/neurotransmitters and growth factors is needed for stimulation of numerous important cellular signaling cascades.

    PubMed

    Sancho, Veronica; Berna, Marc J; Thill, Michelle; Jensen, R T

    2011-12-01

    The novel PKCθ isoform is highly expressed in T-cells, brain and skeletal muscle and originally thought to have a restricted distribution. It has been extensively studied in T-cells and shown to be important for apoptosis, T-cell activation and proliferation. Recent studies showed its presence in other tissues and importance in insulin signaling, lung surfactant secretion, intestinal barrier permeability, platelet and mast-cell functions. However, little information is available for PKCθ activation by gastrointestinal (GI) hormones/neurotransmitters and growth factors. In the present study we used rat pancreatic acinar cells to explore their ability to activate PKCθ and the possible interactions with important cellular mediators of their actions. Particular attention was paid to cholecystokinin (CCK), a physiological regulator of pancreatic function and important in pathological processes affecting acinar function, like pancreatitis. PKCθ-protein/mRNA was present in the pancreatic acini, and T538-PKCθ phosphorylation/activation was stimulated only by hormones/neurotransmitters activating phospholipase C. PKCθ was activated in time- and dose-related manner by CCK, mediated 30% by high-affinity CCK(A)-receptor activation. CCK stimulated PKCθ translocation from cytosol to membrane. PKCθ inhibition (by pseudostrate-inhibitor or dominant negative) inhibited CCK- and TPA-stimulation of PKD, Src, RafC, PYK2, p125(FAK) and IKKα/β, but not basal/stimulated enzyme secretion. Also CCK- and TPA-induced PKCθ activation produced an increment in PKCθ's direct association with AKT, RafA, RafC and Lyn. These results show for the first time the PKCθ presence in pancreatic acinar cells, its activation by some GI hormones/neurotransmitters and involvement in important cell signaling pathways mediating physiological responses (enzyme secretion, proliferation, apoptosis, cytokine expression, and pathological responses like pancreatitis and cancer growth).

  13. A skeleton-tree-based approach to acinar morphometric analysis using microcomputed tomography with comparison of acini in young and old C57BL/6 mice.

    PubMed

    Kizhakke Puliyakote, Abhilash S; Vasilescu, Dragoş M; Sen Sharma, Kriti; Wang, Ge; Hoffman, Eric A

    2016-06-15

    We seek to establish a method using interior tomographic techniques (Xradia MicroXCT-400) for acinar morphometric analysis using the pathway center lines from micro X-ray computed tomographic (Micro-CT) images as the road map. Through the application of these techniques, we present a method to extend the atlas of murine lungs to acinar levels and present a comparison between two age groups of the C57BL/6 strain. Lungs fixed via vascular perfusion were scanned using high-resolution Micro-CT protocols. Individual acini were segmented, and skeletonized paths to alveolar sacs from the entrance to the acinus were formed. Morphometric parameters, including branch lengths, diameters, and branching angles, were generated. Six mice each, at two age groups (∼20 and ∼90 wk of age), were studied. Additive Gaussian noise (0 mean and SD 1, 2, 5, and 10) was used to test the robustness of the analytical method. Noise-based variations were within ±6 μm for branch lengths and ±5 μm for diameters. At a noise level of 10, errors increased. Branch diameters were less susceptible to noise than lengths. There was >95% center line overlap across all noise levels. The measurements obtained using the center lines as a road map were not affected by added noise. Acini from younger mice had smaller branch diameters and lengths at all generations without significant differences in branching angles. The relative distribution of volume in the alveolar ducts was similar across both age groups. The method has been demonstrated to be repeatable and robust to image noise and provides a new, nondestructive technique to assess and compare acinar morphometry quantitatively.

  14. Damage to pancreatic acinar cells and preservation of islets of Langerhans in a rat model of acute pancreatitis induced by Karwinskia humboldtiana (buckthorn).

    PubMed

    Carcano-Diaz, Katya; Garcia-Garcia, Aracely; Segoviano-Ramirez, Juan Carlos; Rodriguez-Rocha, Humberto; Loera-Arias, Maria de Jesus; Garcia-Juarez, Jaime

    2016-09-01

    Karwinskia humboldtiana (Kh) is a poisonous plant that grows in some regions of the American continent. Consuming large amounts of Kh fruit results in acute intoxication leading to respiratory failure, culminating in death within days. There is evidence of histological damage to the lungs, liver, and kidneys following accidental and experimental Kh intoxication. To date, the microscopic effect of Kh consumption on the pancreas has not been described. We examined the early effects of Kh fruit on pancreatic tissue at different stages of acute intoxication in the Wistar rat. We found progressive damage confined to the exocrine pancreas, starting with a reduction in the number of zymogen granules, loss of acinar architecture, the presence of autophagy-like vesicles, apoptosis and inflammatory infiltrate. The pancreatic pathology culminated in damaged acini characterized by necrosis and edema, with a complete loss of lobular architecture. Interestingly, the morphology of the islets of Langerhans was conserved throughout our evaluations. Taken together, our results indicate the damage induced by a high dose of Kh fruit in the Wistar rat is consistent with an early acute necrotizing pancreatitis that exclusively affects the exocrine pancreas. Therefore, this system might be useful as an animal model to study the treatment of pancreatic diseases. More importantly, as the islets of Langerhans were preserved, the active compounds of Kh fruit could be utilized for the treatment of acinar pancreatic cancer. Further studies might provide insight into the severity of acute Kh intoxication in humans and influence the design of treatments for pancreatic diseases and acinar pancreatic cancer.

  15. Autophagy in pancreatic acinar cells in caerulein-treated mice: immunolocalization of related proteins and their potential as markers of pancreatitis.

    PubMed

    Zhang, Leshuai; Zhang, Jun; Shea, Katherine; Xu, Lin; Tobin, Grainne; Knapton, Alan; Sharron, Stewart; Rouse, Rodney

    2014-01-01

    Drug-induced pancreatitis (DIP) is an underdiagnosed condition that lacks sensitive and specific biomarkers. To better understand the mechanisms of DIP and to identify potential tissue biomarkers, we studied experimental pancreatitis induced in male C57BL/6 mice by intraperitoneal injection of caerulein (10 or 50 μg/kg) at 1-hr intervals for a total of 7 injections. Pancreata from caerulein-treated mice exhibited consistent acinar cell autophagy and apoptosis with infrequent necrosis. Kinetic assays for serum amylase and lipase also showed a dose-dependent increase. Terminal deoxynucleotidyl transferase-mediated biotin-dNTP nick labeling (TUNEL) detected dose-dependent acinar cell apoptosis. By light microscopy, autophagy was characterized by the formation of autophagosomes and autolysosomes (ALs) within the cytoplasm of acinar cells. Immunohistochemical studies with specific antibodies for proteins related to autophagy and pancreatic stress were conducted to evaluate these proteins as potential biomarkers of pancreatitis. Western blots were used to confirm immunohistochemical results using pancreatic lysates from control and treated animals. Autophagy was identified as a contributing process in caerulein-induced pancreatitis and proteins previously associated with autophagy were upregulated following caerulein treatment. Autophagosomes and ALs were found to be a common pathway, in which cathepsins, lysosome-associated membrane protein 2, vacuole membrane protein 1, microtubule-associated protein 1 light chain 3 (LC3), autophagy-related protein 9, Beclin1, and pancreatitis-associated proteins were simultaneously involved in response to caerulein stimulus. Regenerating islet-derived 3 gamma (Reg3γ), a pancreatic acute response protein, was dose-dependently induced in caerulein-treated mice and colocalized with the autophagosomal marker, LC3. This finding supports Reg3γ as a candidate biomarker for pancreatic injury.

  16. PKCθ activation in pancreatic acinar cells by gastrointestinal hormones/neurotransmitters and growth factors is needed for stimulation of numerous important cellular signaling cascades

    PubMed Central

    Sancho, Veronica; Berna, Marc J.; Thill, Michelle; Jensen, R. T.

    2011-01-01

    The novel PKCθ isoform is highly expressed in T-cells, brain and skeletal muscle and originally thought to have a restricted distribution. It has been extensively studied in T-cells and shown to be important for apoptosis, T-cell activation and proliferation. Recent studies showed its presence in other tissues and importance in insulin signaling, lung surfactant secretion, intestinal barrier permeability, platelet and mast-cell functions. However, little information is available for PKCθ activation by gastrointestinal(GI) hormones/neurotransmitters and growth factors. In the present study we used rat pancreatic acinar cells to explore their ability to activate PKCθ and the possible interactions with important cellular mediators of their actions. Particular attention was paid to cholecystokinin(CCK), a physiological regulator of pancreatic function and important in pathological processes affecting acinar function, like pancreatitis. PKCθ-protein/mRNA were present in the pancreatic acini, and T538-PKCθ phosphorylation/activation was stimulated only by hormones/neurotransmitters activating phospholipase C. PKCθ was activated in time- and dose-related manner by CCK, mediated 30% by high-affinity CCKA-receptor activation. CCK stimulated PKCθ translocation from cytosol to membrane. PKCθ inhibition (by pseudostrate-inhibitor or dominant negative) inhibited CCK- and TPA-stimulation of PKD, Src, RafC, PYK2, p125FAK and IKKα/β, but not basal/stimulated enzyme secretion. Also CCK- and TPA-induced PKCθ activation produced an increment in PKCθ’s direct association with AKT, RafA, RafC and Lyn. These results show for the first time PKCθ presence in pancreatic acinar cells, its activation by some GI hormones/neurotransmitters and involvement in important cell signaling pathways mediating physiological responses (enzyme secretion, proliferation, apoptosis, cytokine expression, and pathological responses like pancreatitis and cancer growth). PMID:21810446

  17. Monitoring Dosimetric Impact of Weight Loss With Kilovoltage (KV) Cone Beam CT (CBCT) During Parotid-Sparing IMRT and Concurrent Chemotherapy

    SciTech Connect

    Ho, Kean Fatt; Marchant, Tom; Moore, Chris; Webster, Gareth; Rowbottom, Carl; Penington, Hazel; Lee, Lip; Yap, Beng; Sykes, Andrew; Slevin, Nick

    2012-03-01

    Purpose: Parotid-sparing head-and-neck intensity-modulated radiotherapy (IMRT) can reduce long-term xerostomia. However, patients frequently experience weight loss and tumor shrinkage during treatment. We evaluate the use of kilovoltage (kV) cone beam computed tomography (CBCT) for dose monitoring and examine if the dosimetric impact of such changes on the parotid and critical neural structures warrants replanning during treatment. Methods and materials: Ten patients with locally advanced oropharyngeal cancer were treated with contralateral parotid-sparing IMRT concurrently with platinum-based chemotherapy. Mean doses of 65 Gy and 54 Gy were delivered to clinical target volume (CTV)1 and CTV2, respectively, in 30 daily fractions. CBCT was prospectively acquired weekly. Each CBCT was coregistered with the planned isocenter. The spinal cord, brainstem, parotids, larynx, and oral cavity were outlined on each CBCT. Dose distributions were recalculated on the CBCT after correcting the gray scale to provide accurate Hounsfield calibration, using the original IMRT plan configuration. Results: Planned contralateral parotid mean doses were not significantly different to those delivered during treatment (p > 0.1). Ipsilateral and contralateral parotids showed a mean reduction in volume of 29.7% and 28.4%, respectively. There was no significant difference between planned and delivered maximum dose to the brainstem (p = 0.6) or spinal cord (p = 0.2), mean dose to larynx (p = 0.5) and oral cavity (p = 0.8). End-of-treatment mean weight loss was 7.5 kg (8.8% of baseline weight). Despite a {>=}10% weight loss in 5 patients, there was no significant dosimetric change affecting the contralateral parotid and neural structures. Conclusions: Although patient weight loss and parotid volume shrinkage was observed, overall, there was no significant excess dose to the organs at risk. No replanning was felt necessary for this patient cohort, but a larger patient sample will be investigated

  18. Behavioral fever in newborn rabbits

    NASA Technical Reports Server (NTRS)

    Satinoff, E.; Mcewen, G. N., Jr.; Williams, B. A.

    1976-01-01

    New Zealand white rabbit pups aged 12 to 72 hr were divided into three groups and given an intraperitoneal injection of Pseudomonas polysaccharide, a saline vehicle alone, and no treatment, respectively. The animals injected with pyrogen and maintained at an ambient temperature of 32 C for 2 hr did not develop fever. When placed in a thermally graded alleyway, the animals injected with pyrogen selected gradient positions that represented significantly higher temperatures than controls injected with saline. Further stay at selected positions for 5 min caused a considerable increase in the rectal temperature of the pyrogen-injected pups but not that of controls. The results support the hypothesis that newborn rabbits will develop a fever by behavioral means after a single injection of an exogenous pyrogen if the opportunity for thermoregulatory behavior is present. No fever develops if the pups must rely solely on internal thermoregulatory mechanisms. The behavioral system for producing a fever is mature at birth, but an adequate system of internal reflexes does not appear to develop for some days.

  19. Impact of Node Negative Target Volume Delineation on Contralateral Parotid Gland Dose Sparing Using IMRT in Head and Neck Cancer.

    PubMed

    Magnuson, William J; Urban, Erich; Bayliss, R Adam; Harari, Paul M

    2015-06-01

    There is considerable practice variation in treatment of the node negative (N0) contralateral neck in patients with head and neck cancer. In this study, we examined the impact of N0 neck target delineation volume on radiation dose to the contralateral parotid gland. Following institutional review board approval, 12 patients with head and neck cancer were studied. All had indications for treatment of the N0 neck, such as midline base of tongue or soft palate extension or advanced ipsilateral nodal disease. The N0 neck volumes were created using the Radiation Therapy Oncology Group head and neck contouring atlas. The physician-drawn N0 neck clinical target volume (CTV) was expanded by 25% to 200% to generate volume variation, followed by a 3-mm planning target volume (PTV) expansion. Surrounding organs at risk were contoured and complete intensity-modulated radiation therapy plans were generated for each N0 volume expansion. The median N0 target volume drawn by the radiation oncologist measured 93 cm(3) (range 71-145). Volumetric expansion of the N0 CTV by 25% to 200% increased the resultant mean dose to the contralateral parotid gland by 1.4 to 8.5 Gray (Gy). For example, a 4.1-mm increase in the N0 neck CTV translated to a 2.0-Gy dose increase to the parotid, 7.4 mm to a 4.5 Gy dose increase, and 12.5 mm to an 8.5 Gy dose increase, respectively. The treatment volume designated for the N0 neck has profound impact on resultant dose to the contralateral parotid gland. Variations of up to 15 mm are routine across physicians in target contouring, reflecting individual preference and training expertise. Depending on the availability of immobilization and image guidance techniques, experts commonly recommend 3 to 10 mm margin expansions to generate the PTV. Careful attention to the original volume of the N0 neck CTV, as well as expansion margins, is important in achieving effective contralateral gland sparing to reduce the resultant xerostomia and dysguesia that may ensue

  20. Secondary radiation damage as the main cause for unexpected volume effects: A histopathologic study of the parotid gland

    SciTech Connect

    Konings, Antonius W.T. . E-mail: a.w.t.konings@med.umcg.nl; Faber, Hette; Cotteleer, Femmy; Vissink, Arjan; Coppes, Rob P.

    2006-01-01

    Purpose: To elucidate with a histopathological study the mechanism of region-dependent volume effects in the partly irradiated parotid gland of the rat. Methods and Materials: Wistar rats were locally X-irradiated with collimators with conformal radiation portals for 100% volume and 50% cranial/caudal partial volumes. Single doses up to 40 Gy were applied. Parotid saliva samples were collected, and the three lobes of the parotid gland were examined individually on the macro- and micromorphologic level up to 1 year after irradiation. Results: Dose-dependent loss of gland weight was observed 1 year after total or partial X-irradiation. Weight loss of the glands correlated very well with loss of secretory function. Irradiating the cranial 50% volume (implicating a shielded lateral lobe) resulted in substantially more damage in terms of weight loss and loss of secretory function than 50% caudal irradiation (shielding the ventral and dorsal lobe). Histologic examinations of the glands 1 year after irradiation revealed that the shielded lateral lobe was severely affected, in contrast to the shielded ventral and dorsal lobes. Time studies showed that irradiation of the cranial 50% volume caused late development of secondary damage in the shielded lateral lobe, becoming manifest between 240 and 360 days after irradiation. The possible clinical significance of this finding is discussed. Conclusion: It is concluded that the observed region-dependent volume effect for late function loss in the rat parotid gland after partial irradiation is mainly caused by secondary events in the shielded lateral lobe. The most probable first step (primary radiation event) in the development of this secondary damage is radiation exposure to the hilus region (located between the ventral and dorsal lobe). By injuring major excretory ducts and supply routes for blood and nerves in this area, the facility system necessary for proper functioning of the nonexposed lateral lobe is seriously affected

  1. 9 CFR 354.124 - Quarantine of diseased rabbits.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Quarantine of diseased rabbits. 354... INSPECTION AND CERTIFICATION VOLUNTARY INSPECTION OF RABBITS AND EDIBLE PRODUCTS THEREOF Inspection Procedures; Ante-Mortem Inspections § 354.124 Quarantine of diseased rabbits. If live rabbits, which...

  2. 9 CFR 354.124 - Quarantine of diseased rabbits.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Quarantine of diseased rabbits. 354... INSPECTION AND CERTIFICATION VOLUNTARY INSPECTION OF RABBITS AND EDIBLE PRODUCTS THEREOF Inspection Procedures; Ante-Mortem Inspections § 354.124 Quarantine of diseased rabbits. If live rabbits, which...

  3. 9 CFR 354.124 - Quarantine of diseased rabbits.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Quarantine of diseased rabbits. 354... INSPECTION AND CERTIFICATION VOLUNTARY INSPECTION OF RABBITS AND EDIBLE PRODUCTS THEREOF Inspection Procedures; Ante-Mortem Inspections § 354.124 Quarantine of diseased rabbits. If live rabbits, which...

  4. 9 CFR 354.124 - Quarantine of diseased rabbits.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Quarantine of diseased rabbits. 354... INSPECTION AND CERTIFICATION VOLUNTARY INSPECTION OF RABBITS AND EDIBLE PRODUCTS THEREOF Inspection Procedures; Ante-Mortem Inspections § 354.124 Quarantine of diseased rabbits. If live rabbits, which...

  5. Factors affecting rabbit meat consumption among Spanish university students.

    PubMed

    González-Redondo, Pedro; Mena, Yolanda; Fernández-Cabanás, Victor M

    2010-01-01

    This study investigates the rabbit meat consumption patterns among students. Results of the 342 students surveyed at the University of Seville, Spain showed that more men than women consumed rabbit meat. More students consumed wild rabbit meat than farmed rabbit meat. The practice of hunting by students or their relatives, and the raising of rabbits for self-consumption, positively influenced the proportion of students that currently consumed rabbit meat. Most of the students that had eaten rabbit meat before but are currently non-eaters do so because of the meat's organoleptic characteristics or from lack of consumption habit.

  6. Encephalitozoon cuniculi in rabbits: Serological screening and histopathological findings.

    PubMed

    Maestrini, Giovanni; Ricci, Emanuele; Cantile, Carlo; Mannella, Riccardo; Mancianti, Francesca; Paci, Gisella; D'Ascenzi, Carlo; Perrucci, Stefania

    2017-02-01

    Serological prevalence of E. cuniculi infection was assessed in 183 rabbits from central Italy. In seropositive deceased rabbits, histopathological lesions were also evaluated. Sera from 118 rabbits from 6 intensive farms, 10 rabbits from 6 family farms, 16 rabbits from a zoo, 30 rabbits from 5 research laboratories and 9 pet rabbits from 9 different owners, were tested by an enzyme-linked immunosorbent assay. Data were statistically analysed. Tissue samples from brain and kidney of 10 deceased rabbits were formalin-fixed and subsequently analysed by histopathology and immunohistochemistry. Anti-E. cuniculi antibodies were found in 129/183 (70.5%) analysed sera. At statistical analysis, E. cuniculi seropositivity was significantly higher (p<0.05) in industrial and zoo rabbits. At histology, different degrees of pathological lesions were found in serological positive (9) deceased animals. In three rabbits deceased after showing neurological signs, the severity of the lesions was interpreted as a likely cause for their death.

  7. Bobcat attack on a cottontail rabbit

    USGS Publications Warehouse

    Biggins, D.E.; Biggins, D.M.

    2006-01-01

    We observed an attack by a bobcat (Lynx rufus) on a cottontail rabbit (Sylvilagus) that involved stealthy approach by the cat for >1 h, followed by a 12.3-s chase covering 116.0 m for the cat and 128.4 m for the rabbit. During the chase, the route of the cat from starting point to kill site was more direct than the semi-circular route of the rabbit. Stride lengths for the cat and total distance covered by the chase were longer than those previously reported for bobcats.

  8. Stimulus-secretion coupling in pancreatic acinar cells: inhibitory effects of calcium removal and manganese addition on pancreozymin-induced amylase release.

    PubMed Central

    Kanno, T; Nishimura, O

    1976-01-01

    The role of Ca ions in stimulus-secretion coupling has been analysed in the isolated and perfused rat pancreas. 2. The omission of [Ca2+]O diminished but did not abolish the release of amylase in response to continuous stimulation with 5 m-u. pancreozymin (Pz)/ml. The addition of Mn2+ (1-0 mM) to this Ca-deficient environment abolished the residual release of amylase. This was followed by a complete recovery of amylase output when the control [Ca2+]O was reestablished. 3. The addition of Mn2+ (1-0 mM) to the extracellular environment containing 2-5 mM-Ca2+ reversibly inhibited the Pz-induced release of amylase. 4. A kinetic scheme based on competition of Ca and Mn at a carrier in the acinar cell membrane could quantitatively explain the effects of Ca and Mn upon the Pz-induced amylase release. 5. These results support the view that the Ca2+ influx into the acinar cells is the major contributor to the rise in [Ca2+]i which, in turn, mediates the processes in the stimulus-secretion coupling in the exocrine pancreas, and suggest that the mode of Ca influx is a facilitated diffusion. PMID:950596

  9. RAS inhibitors decrease apoptosis of acinar cells and increase elimination of pancreatic stellate cells after in the course of experimental chronic pancreatitis induced by dibutyltin dichloride.

    PubMed

    Madro, A; Korolczuk, A; Czechowska, G; Celiński, K; Słomka, M; Prozorow-Król, B; Korobowicz, E

    2008-08-01

    Chronic pancreatitis (CP) is a progressive disease, in which the exocrine function of the gland is gradually lost and fibrosis develops due to repeated episodes of acute pancreatitis. The aim of the study was to investigate the effects of RAS inhibitors on the apoptosis of acinar cells and pancreatic stellate cells (PSCs) elimination in experimental CP induced by dibutyltin dichloride (DBTC). CP was induced by administration of DBTC to the femoral vein. Simultaneously captopril, losartan, enalapril and lisinopril were administered intraperitoneally. The rats were decapitated after 60 days and tissue of pancreas was collected. In rats treated by DBTC the features of inflammatory infiltration, ductal lumen dilatation, fibrosis were found. Strong reactivity with caspase2(L) and clusterin-beta antibodies was observed in areas of fibrosis. In animals treated with RAS inhibitors inflammatory changes and fibrosis were less severe. In groups of rats treated with DBTC and RAS inhibitors immunoreactivity of caspase(2L) and clusterin-beta was weak. Positive immunostaining against smooth muscle actine and desmin was observed in the elongated cells (PSC-s). This reaction was weak in groups of rat treated with DBTC and RAS inhibitors. Treatment of CP rats with RAS inhibitors alleviate apoptosis of pancreatic acinar cells and induces PSCs elimination.

  10. Quantitative characterization of the protein contents of the exocrine pancreatic acinar cell by soft x-ray microscopy and advanced digital imaging methods

    SciTech Connect

    Loo, Jr., Billy W.

    2000-06-01

    The study of the exocrine pancreatic acinar cell has been central to the development of models of many cellular processes, especially of protein transport and secretion. Traditional methods used to examine this system have provided a wealth of qualitative information from which mechanistic models have been inferred. However they have lacked the ability to make quantitative measurements, particularly of the distribution of protein in the cell, information critical for grounding of models in terms of magnitude and relative significance. This dissertation describes the development and application of new tools that were used to measure the protein content of the major intracellular compartments in the acinar cell, particularly the zymogen granule. Soft x-ray microscopy permits image formation with high resolution and contrast determined by the underlying protein content of tissue rather than staining avidity. A sample preparation method compatible with x-ray microscopy was developed and its properties evaluated. Automatic computerized methods were developed to acquire, calibrate, and analyze large volumes of x-ray microscopic images of exocrine pancreatic tissue sections. Statistics were compiled on the protein density of several organelles, and on the protein density, size, and spatial distribution of tens of thousands of zymogen granules. The results of these measurements, and how they compare to predictions of different models of protein transport, are discussed.

  11. Clinical and radiological evidence to support superficial parotidectomy as the treatment of choice for chronic parotid sialadenitis: a retrospective study.

    PubMed

    Amin, M A; Bailey, B M; Patel, S R

    2001-10-01

    We present a retrospective series of 23 consecutive parotidectomies, over a 10-year period (1989-1999) for 22 patients with chronic sialadenitis unresponsive to conservative measures. There were 10 male and 12 female patients. Mean age was 52 years (range 12-72), and mean duration of symptoms 4.5 years (range 8 months-30 years). All patients had preoperative sialography and 2 had computed tomography to exclude a neoplasm. A complete superficial parotidectomy with preservation of the main duct was done in all cases. Fifteen patients developed temporary facial nerve weakness postoperatively and 7 developed Frey's syndrome. There were no cases of permanent facial nerve palsy. Nineteen patients reported complete resolution of their symptoms and 3 patients had mild persisting symptoms that did not necessitate any further treatment. Histologically there was evidence of sialadenosis in one case and benign lymphoepithelial lesion in another; the others showed evidence of chronic sialadenitis of varying degrees of severity. Fifteen patients had postoperative sialograms, of which 11 showed evidence of some filling of residual parotid gland parenchyma and in 8 patients there was filling of a normal-looking accessory lobe. In this series, superficial parotidectomy with preservation of the main duct was safe and effective, with minimal long-term complications, for most patients with chronic parotid sialadenitis that was unresponsive to conservative measures and, in some patients, it allowed some preservation of function. The potential damage to the facial nerve and the cosmetic problems associated with a total or near-total parotidectomy were avoided.

  12. Metabolism of hydroanthracenones in rabbits

    PubMed Central

    Robertson, J. S.; Dunstan, P. J.

    1972-01-01

    1. The metabolism of 1-oxo-octahydro- and 2- and 9-oxoperhydro-anthracenes was investigated in rabbits. All compounds increased the urinary glucuronide content. 2. The 1-oxo and 2-oxo compounds were reduced to the corresponding alcohols whereas the 9-oxo compound was hydroxylated. 3. The reduction in vitro of these compounds and related ketones was investigated with three different enzyme systems (liver alcohol dehydrogenase, hydroxy steroid dehydrogenase, aromatic aldehyde–ketone reductase) in an attempt to explain the results in vivo. 4. Successful reduction of many ketones with aromatic aldehyde–ketone reductase suggests that the kidney may be of importance in the reduction in vivo of certain cyclic carbonyl compounds. PMID:5073736

  13. [Possible relation between viruses and oromaxillofacial tumors. IV. Presence of the herpes antigen and anti-herpes antibodies in patients with tumors of the parotid gland].

    PubMed

    Stoian, M; Suru, M; Zaharia, O; Constantinescu, E; Goldstein, I; Nastac, E

    1987-01-01

    The presence of herpesvirus antigen and of antiherpesvirus antibodies was detected in 46% and in 36.3%, respectively, of the patients bearing parotid gland tumors. Very high titers of antiherpesvirus antibodies were found in 70.6% of the patients with nasopharyngeal carcinoma.

  14. (3H)-isoproterenol binding to subcellular fractions of mouse parotid: relationship to cyclic nucleotide formation and the stimulation of DNA synthesis.

    PubMed

    Durham, J P; Galanti, N

    1976-12-01

    (3H) Isoproterenol binding to subcellular fractions of mouse parotid: Relationship to cyclic nucleotide formation and the stimulation of DNA synthesis. (Unión the (3H) Isoproterenol a fracciones subcelulares de parótida de ratón y su relacón con la formacón de nucleótidos cíclicos y la estimulación de la síntesis de DNA). Arch. Biol. Med. Exper. 10: 105-114, 1976. Tritiated isoproterenol binds to all subcellular fractions of mouse parotid but 70% of the binding is to the nuclear fraction. Binding to other mouse tissues was less than to the parotid. The patterns of binding did not correlate with the distribution of adenylate cyclase, guanylate cyclase or catechol-O-methyl transferase among the fractions or tissues nor with the extent of response in stimulation of DNA synthesis among the tissues. Inhibition of (3H) Isoproterenol binding to parotid fractions by catecholamine analogs was studied. There was no correlation between their ability to inhibit binding and the ability of the analogs themselves to raise cyclic AMP levels or stimulate DNA synthesis.

  15. Quantification of Trade-Off Between Parotid Gland Sparing and Planning Target Volume Underdosages in Clinically Node-Negative Head-and-Neck Intensity-Modulated Radiotherapy

    SciTech Connect

    Kruijf, Wilhelmus de . E-mail: kruijf.de.w@bvi.nl; Heijmen, Ben; Levendag, Peter C.

    2007-05-01

    Purpose: To quantify the trade-off between parotid gland sparing and planning target volume (PTV) underdosages for head-and-neck intensity-modulated radiotherapy. Methods and Materials: A planning study was performed for 4 patients with either soft palate or tonsil tumors treated with external radiotherapy up to 46 Gy. The trade-off between underdosages in the PTV and sparing of the parotid glands was investigated by systematically varying the optimization objectives for the inverse planning. A new way of presenting dose-volume information allows easy detection of small PTV subvolumes with underdosages that cannot be assessed in conventional cumulative dose-volume histograms. A simple radiobiological model to estimate the control probability for an electively irradiated neck level was developed. Results: The average dose to the parotid glands can decrease by >10 Gy by allowing the PTV to be underdosed in such a way that the radiobiological model predicts a decrease in subclinical disease control probability of (typically) 1% to a few percent. Conclusion: The trade-off between parotid gland sparing and underdosages in the PTV has been quantified by the use of an alternative method to present dose-volume information and by the use of a radiobiological model to predict subclinical disease control probability.

  16. Sialendoscopy and sialendoscopically-assisted operations in the treatment of lithiasis of the submandibular and parotid glands: our experience of 239 cases.

    PubMed

    Kopeć, Tomasz; Wierzbicka, Małgorzata; Kałużny, Jarosław; Młodkowska, Anna; Szyfter, Witold

    2016-09-01

    We present the results of treatment of sialolithiasis of the submandibular and parotid glands using sialendoscopy and sialendoscopy-assisted surgery. Between 2009-2013, 397 consecutive patients (mean (range) age 48 (18-76) years) were treated for obstructive diseases of the major salivary glands (sialolithiasis n=239, 175 submandibular and 64 parotid). In a total of 175 patients with 191 stones in the submandibular gland treated by endoscopic retrieval or surgical release, 149 patients (85%) were rendered free of stones (by sialendoscopy alone n=82, and sialendoscopy with operation n=67) Twenty patients (11%) had residual stones and 6 patients (4%) required excisionof the gland. Sixty-four patients had 71 stones removed from the parotid gland by endoscopic retrieval or surgical release and 43 (67%) were free of stones (by sialendoscopy alone n=25, and sialendoscopy with operation n=18). Twenty patients (31%) had residual stones and one (2%) required removal of the gland. In the group of patients whose stones were removed endoscopically, the effectiveness of sialendoscopy was 87% and 85%, respectively. We confirm that sialendoscopy and sialendoscopy-assisted removal is the current treatment of choice for stones in the submandibular and parotid glands. The indications for excision of the gland are becoming less common as first-line treatment, although it is still indispensable in some cases.

  17. TH-E-BRF-09: Gaussian Mixture Model Analysis of Radiation-Induced Parotid-Gland Injury: An Ultrasound Study of Acute and Late Xerostomia in Head-And-Neck Radiotherapy

    SciTech Connect

    Liu, T; Yu, D; Beitler, J; Curran, W; Yang, X; Tridandapani, S; Bruner, D

    2014-06-15

    Purpose: Xerostomia (dry mouth), secondary to parotid-gland injury, is a distressing side-effect in head-and-neck radiotherapy (RT). This study's purpose is to develop a novel ultrasound technique to quantitatively evaluate post-RT parotid-gland injury. Methods: Recent ultrasound studies have shown that healthy parotid glands exhibit homogeneous echotexture, whereas post-RT parotid glands are often heterogeneous, with multiple hypoechoic (inflammation) or hyperechoic (fibrosis) regions. We propose to use a Gaussian mixture model to analyze the ultrasonic echo-histogram of the parotid glands. An IRB-approved clinical study was conducted: (1) control-group: 13 healthy-volunteers, served as the control; (2) acutetoxicity group − 20 patients (mean age: 62.5 ± 8.9 years, follow-up: 2.0±0.8 months); and (3) late-toxicity group − 18 patients (mean age: 60.7 ± 7.3 years, follow-up: 20.1±10.4 months). All patients experienced RTOG grade 1 or 2 salivary-gland toxicity. Each participant underwent an ultrasound scan (10 MHz) of the bilateral parotid glands. An echo-intensity histogram was derived for each parotid and a Gaussian mixture model was used to fit the histogram using expectation maximization (EM) algorithm. The quality of the fitting was evaluated with the R-squared value. Results: (1) Controlgroup: all parotid glands fitted well with one Gaussian component, with a mean intensity of 79.8±4.9 (R-squared>0.96). (2) Acute-toxicity group: 37 of the 40 post-RT parotid glands fitted well with two Gaussian components, with a mean intensity of 42.9±7.4, 73.3±12.2 (R-squared>0.95). (3) Latetoxicity group: 32 of the 36 post-RT parotid fitted well with 3 Gaussian components, with mean intensities of 49.7±7.6, 77.2±8.7, and 118.6±11.8 (R-squared>0.98). Conclusion: RT-associated parotid-gland injury is common in head-and-neck RT, but challenging to assess. This work has demonstrated that the Gaussian mixture model of the echo-histogram could quantify acute and late

  18. Rabbit haemorrhagic disease: field epidemiology and the management of wild rabbit populations.

    PubMed

    Cooke, B D

    2002-08-01

    Rabbit haemorrhagic disease (RHD) has become established in wild rabbit populations throughout Western Europe, Australia and New Zealand. The abundance of wild rabbits has been significantly reduced, particularly in drier areas of southern Spain, inland Australia and South Island New Zealand. A detailed knowledge of the epidemiology of RHD is essential for the management of the disease in natural rabbit populations, either to rebuild or to control populations. When RHD first spread among naive wild rabbits, epidemiological studies provided unique information on the rate of spread, the possible role of insect vectors in transmission, and the correlation between the impact of disease on populations and climatic variables. Current research shows a consistent pattern of epidemiology between Europe and Australasia. Typically, the most severe epizootics of RHD occur among young sub-adult rabbits which have lost age-related resilience and maternal antibodies. However, the timing of these outbreaks reflects climatic variables that determine the breeding season of the rabbits and the periods when RHD virus (RDHV) is most likely to persist and spread. Further factors that may complicate epidemiology include the possibility that non-pathogenic RHDV-like viruses are present in natural rabbit populations. Additionally, the question of how the virus persists from year to year remains unresolved; persistence in carrier rabbits is a possibility. Understanding of the epidemiology of RHD is now sufficiently advanced to consider the possibility of manipulating rabbit populations to alter the epidemiological pattern of RHD and thereby maximise or minimise the mortality caused by the disease. Altering the epidemiology of RHD in this manner would assist the management of wild rabbit populations either for conservation or pest control purposes.

  19. Genomic Analysis of Companion Rabbit Staphylococcus aureus

    PubMed Central

    Holmes, Mark A.; Harrison, Ewan M.; Fisher, Elizabeth A.; Graham, Elizabeth M.; Parkhill, Julian; Foster, Geoffrey; Paterson, Gavin K.

    2016-01-01

    In addition to being an important human pathogen, Staphylococcus aureus is able to cause a variety of infections in numerous other host species. While the S. aureus strains causing infection in several of these hosts have been well characterised, this is not the case for companion rabbits (Oryctolagus cuniculus), where little data are available on S. aureus strains from this host. To address this deficiency we have performed antimicrobial susceptibility testing and genome sequencing on a collection of S. aureus isolates from companion rabbits. The findings show a diverse S. aureus population is able to cause infection in this host, and while antimicrobial resistance was uncommon, the isolates possess a range of known and putative virulence factors consistent with a diverse clinical presentation in companion rabbits including severe abscesses. We additionally show that companion rabbit isolates carry polymorphisms within dltB as described as underlying host-adaption of S. aureus to farmed rabbits. The availability of S. aureus genome sequences from companion rabbits provides an important aid to understanding the pathogenesis of disease in this host and in the clinical management and surveillance of these infections. PMID:26963381

  20. Parotid Glands Dose–Effect Relationships Based on Their Actually Delivered Doses: Implications for Adaptive Replanning in Radiation Therapy of Head-and-Neck Cancer

    SciTech Connect

    Hunter, Klaudia U.; Fernandes, Laura L.; Vineberg, Karen A.; McShan, Daniel; Antonuk, Alan E.; Cornwall, Craig; Feng, Mary; Schipper, Mathew J.; Balter, James M.; Eisbruch, Avraham

    2013-11-15

    Purpose: Doses actually delivered to the parotid glands during radiation therapy often exceed planned doses. We hypothesized that the delivered doses correlate better with parotid salivary output than the planned doses, used in all previous studies, and that determining these correlations will help make decisions regarding adaptive radiation therapy (ART) aimed at reducing the delivered doses. Methods and Materials: In this prospective study, oropharyngeal cancer patients treated definitively with chemoirradiation underwent daily cone-beam computed tomography (CBCT) with clinical setup alignment based on the C2 posterior edge. Parotid glands in the CBCTs were aligned by deformable registration to calculate cumulative delivered doses. Stimulated salivary flow rates were measured separately from each parotid gland pretherapy and periodically posttherapy. Results: Thirty-six parotid glands of 18 patients were analyzed. Average mean planned doses was 32 Gy, and differences from planned to delivered mean gland doses were −4.9 to +8.4 Gy, median difference +2.2 Gy in glands in which delivered doses increased relative to planned. Both planned and delivered mean doses were significantly correlated with posttreatment salivary outputs at almost all posttherapy time points, without statistically significant differences in the correlations. Large dispersions (on average, SD 3.6 Gy) characterized the dose–effect relationships for both. The differences between the cumulative delivered doses and planned doses were evident at first fraction (r=.92, P<.0001) because of complex setup deviations (eg, rotations and neck articulations), uncorrected by the translational clinical alignments. Conclusions: After daily translational setup corrections, differences between planned and delivered doses in most glands were small relative to the SDs of the dose–saliva data, suggesting that ART is not likely to gain measurable salivary output improvement in most cases. These differences were

  1. A Comparison of Dose-Response Models for the Parotid Gland in a Large Group of Head-and-Neck Cancer Patients

    SciTech Connect

    Houweling, Antonetta C.; Philippens, Marielle E.P.; Dijkema, Tim; Roesink, Judith M.; Terhaard, Chris H.J.; Schilstra, Cornelis; Ten Haken, Randall K.; Eisbruch, Avraham; Raaijmakers, Cornelis P.J.

    2010-03-15

    Purpose: The dose-response relationship of the parotid gland has been described most frequently using the Lyman-Kutcher-Burman model. However, various other normal tissue complication probability (NTCP) models exist. We evaluated in a large group of patients the value of six NTCP models that describe the parotid gland dose response 1 year after radiotherapy. Methods and Materials: A total of 347 patients with head-and-neck tumors were included in this prospective parotid gland dose-response study. The patients were treated with either conventional radiotherapy or intensity-modulated radiotherapy. Dose-volume histograms for the parotid glands were derived from three-dimensional dose calculations using computed tomography scans. Stimulated salivary flow rates were measured before and 1 year after radiotherapy. A threshold of 25% of the pretreatment flow rate was used to define a complication. The evaluated models included the Lyman-Kutcher-Burman model, the mean dose model, the relative seriality model, the critical volume model, the parallel functional subunit model, and the dose-threshold model. The goodness of fit (GOF) was determined by the deviance and a Monte Carlo hypothesis test. Ranking of the models was based on Akaike's information criterion (AIC). Results: None of the models was rejected based on the evaluation of the GOF. The mean dose model was ranked as the best model based on the AIC. The TD{sub 50} in these models was approximately 39 Gy. Conclusions: The mean dose model was preferred for describing the dose-response relationship of the parotid gland.

  2. Purification and characterization of a rabbit salivary protein, a potent inhibitor of crystal growth of calcium phosphate salts.

    PubMed

    Spielman, A I; Bernstein, A; Hay, D I; Blum, M; Bennick, A

    1991-01-01

    Human saliva is supersaturated with respect to basic calcium phosphate salts but is stabilized by specific macromolecules that inhibit calcium phosphate precipitation. One of the families of inhibitory proteins in human and monkey saliva is the acidic proline-rich proteins. The purpose of this study was to isolate and characterize inhibitors of calcium phosphate precipitation from rabbit parotid saliva. Saliva was fractionated by immunoaffinity chromatography and anion exchange chromatography. Individual fractions were assayed for their ability to inhibit calcium phosphate crystal growth and the fraction associated with the inhibition was purified by repeated anion exchange chromatography, preparative gel electrophoresis and electroelution. A major (APRP) and two minor proteins (AM1, AM2) that were inhibitory were purified. APRP is an acidic proline-rich phospho-glycoprotein and a very potent inhibitor of secondary crystal growth of calcium phosphate as it was active at a concentration of 2 x 10(-8) M in a standard assay. The N-terminal sequence of one APRP was EYENLDGSLAATQNDDD?Q and a clostripain fragment of APRP had the following N-terminal sequence PQHRPPRPGGH-????SPPP?GN???PPP. Although the N-terminal segment of APRP does not resemble that of proline-rich proteins, alignment of the clostripain fragment with the repeat region of such proteins from rat, mouse, monkey and man revealed a high degree of similarity, indicating a structural relationship with the proline-rich protein family.

  3. Experimental Toxoplasmic Lymphadenopathy in Rabbits

    PubMed Central

    Henry, L.; Beverley, J. K. A.; Shortland, J. R.; Coup, A. J.

    1973-01-01

    The pathogenesis of toxoplasmic lymphadenopathy was studied in rabbits. Sixteen were infected with a high virulence strain of Toxoplasma gondii and 32 with one of low virulence. The former group were killed and examined at intervals up to 9 days and the latter up to 129 days. The high virulence strain quickly caused paracortical hyperplasia but only moderate follicular reaction. Later, lymphoid depletion occurred. The low virulence strain caused follicular reaction so that at 16 days germinal centres had developed with evidence of cellular phagocytosis. Histiocytes were present and plasma cells were found in the medullary cords. These appearances were seen up to 51 days. At 86 days the follicular reaction was no longer present but had returned at 129 days. These results were supplemented by serological, parasitological, immunofluorescence and electron microscopic data. The histological changes seen in the low virulence infections up to 51 days are unlike those caused by the high virulence strain but closely parallel those found in acquired infections in man, which are usually caused by strains of the low virulence type. These findings may help to elucidate the nature of the complex immune responses and the pathogenesis of toxoplasma infections. ImagesFigs. 14-15Figs. 16, 18 and 19Figs. 12-13Figs. 7-11Figs. 1-6 PMID:4577945

  4. Complicated coexisting pyogenic and tuberculous otitis media affecting the temporozygomatic, infratemporal, and parotid areas: report of a rare entity.

    PubMed

    Brar, Tripti; Mrig, Sumit; Passey, J C; Agarwal, A K; Jain, Shayma

    2013-01-01

    We report an unusual case in which a 28-year-old woman presented with a long-standing history of ear discharge, hearing loss, facial weakness with ipsilateral facial swelling and cellulitis, a postauricular fistula, and an abscess of the temporozygomatic, infratemporal, and parotid areas. The pus stained positive for bacteria and acid-fast bacilli, and culture was positive for Proteus vulgaris and mycobacteria. Based on these findings, a diagnosis of tuberculous otitis media with complications was made. Computed tomography showed extensive destruction of the tympanic and mastoid part of the temporal bone, as well as lytic lesions in the skull. The patient was placed on antituberculosis drug therapy. Although her facial nerve palsy and hearing loss persisted, she otherwise responded well and did not require surgery.

  5. Undifferentiated Malignant Neoplasm Involving Parotid and Thyroid: Sampling and PAX8 Cross-Reactivity Can Obscure the Diagnosis of Lymphoma

    PubMed Central

    Nodit, Laurentia; Van Meter, Stuart

    2016-01-01

    Poorly differentiated malignant neoplasia arising within the head and neck region may originate from diverse sources. We report a case of a cytologically undifferentiated malignant neoplasm clinically presenting as masses involving thyroid and parotid. Although PAX8 was immunoreactive and thus worrisome for anaplastic thyroid carcinoma, the tumor was eventually proven to represent PAX5 positive diffuse large B-cell lymphoma expressing cross-reactivity with polyclonal PAX8 antibody. Cross-reactivity between commercially available polyclonal PAX8 and PAX5 immunostains has been described in the literature but is not widely known, and it is a potential pitfall for making a misdiagnosis. This distinction can have importance in selection of subsequent clinical therapy and should be considered in choice of immunohistochemical stains for diagnostic purposes. PMID:28078156

  6. Immediate facial reanimation in oncological parotid surgery with neurorrhaphy of the masseteric-thoracodorsal-facial nerve branch.

    PubMed

    Biglioli, Federico; Tarabbia, Filippo; Allevi, Fabiana; Colombo, Valeria; Giovanditto, Federica; Latiff, Mahfuz; Lozza, Alessandro; Previtera, Antonino; Cupello, Silvia; Rabbiosi, Dimitri

    2016-06-01

    The extracranial facial nerve may be sacrificed together with the parotid gland during a radical parotidectomy, and immediate reconstruction of the facial nerve is essential to maintain at least part of its function. We report five patients who had had radical parotidectomy (two with postoperative radiotherapy) and immediate (n=3) or recent (n=2) reconstructions of the masseteric-thoracodorsal-facial nerve branch. The first mimetic musculature movements started 6.2 (range 4-8.5) months postoperatively. At 24 months postoperatively clinical evaluation (modified House-Brackmann classification) showed grade V (n=3), grade IV (n=1), and grade III (n=1) repairs. This first clinical series of masseteric-thoracodorsal-facial nerve neurorrhaphies has given encouraging results, and the technique should be considered as an option for immediate or recent reconstruction of branches of the facial nerve, particularly when its trunk is not available for proximal neurorrhaphy.

  7. Epithelial-mesenchymal transdifferentiation and extracellular matrix gene expression in pleomorphic adenomas of the parotid salivary gland.

    PubMed

    Aigner, T; Neureiter, D; Völker, U; Belke, J; Kirchner, T

    1998-10-01

    Mesenchymal and epithelial cell differentiation are assumed to be dichotomic primary events in embryonic development. In this study, pleomorphic adenomas of the parotid gland were analysed as a model which shows morphological features of both epithelial and mesenchymal tissue types. Using matrix gene expression profiles as a supplementary criterion for the identification of cellular phenotypes, areas with unequivocal epithelial and mesenchymal differentiation could be demonstrated. Many areas displayed a transitional phenotype with cells showing both epithelial and mesenchymal features. The data provide evidence that epithelial-mesenchymal transitions represent the basic principle of the tisuse heterogeneity in pleomorphic adenomas. Thus, pleomorphic adenomas demonstrate the potential of adult (neoplastic) epithelial cells to transdifferentiate into mesenchymal cells in vivo.

  8. Promoting effect of arachidonic acid supplementation on N-methyl-N-nitrosourea-induced pancreatic acinar cell hyperplasia in young Lewis rats.

    PubMed

    Yoshizawa, Katsuhiko; Uehara, Norihisa; Kimura, Ayako; Emoto, Yuko; Kinoshita, Yuichi; Yuri, Takashi; Takada, Hideho; Moriguchi, Toru; Hamazaki, Tomohito; Tsubura, Airo

    2013-01-01

    Arachidonic acid (AA) is naturally found in human breast milk. AA, together with docosahexaenoic acid, is commonly added as a functional food ingredient to commercial infant formula worldwide, in accordance with the international standard of Codex Alimentarius. However, few studies have been performed that are concerned with the possible carcinogenic effects of AA supplementation during neonatal life. The effect of dietary AA supplementation in dams, during gestation and lactation, was investigated in N-methyl-N-nitrosourea (MNU)-induced preneoplastic lesions in the exocrine pancreas of young Lewis rats. Dams were fed either an AA (2.0% AA) or a basal (<0.01% AA) diet. On postnatal day 0 (at birth), male and female pups received a single intraperitoneal injection of either 35 mg/kg MNU or vehicle. The morphology and proliferating activity of the exocrine pancreas were examined by proliferative cell nuclear antigen immunohistochemistry 7, 14, 21, 28 and/or 60 days post-MNU. Histopathologically, acinar cell hyperplasia (ACH) occurred in the MNU-treated groups 60 days after MNU injection, irrespecitive of whether the rats had been fed an AA diet. Morphometrically, the number and area of ACH per 1 mm(2) in MNU-treated rats increased significantly in the AA diet-fed rats, compared with basal diet-fed rats. The number of proliferative cell nuclear antigen-positive acinar cells in both the normal and hyperplastic areas of MNU-treated rats increased significantly in the AA diet-fed rats. In conclusion, providing dams with an AA-rich diet during gestation and lactation promotes MNU-induced pancreatic ACH in young Lewis rats.

  9. Comparison of several radiation effects in human MCF10A mammary epithelial cells cultured as 2D monolayers or 3D acinar stuctures in matrigel.

    PubMed

    Lin, Yu-Fen; Nagasawa, Hatsumi; Peng, Yuanlin; Chuang, Eric Y; Bedford, Joel S

    2009-06-01

    It has been argued that the cell-cell and cell-matrix interaction networks in normal tissues are disrupted by radiation and that this largely controls many of the most important cellular radiation responses. This has led to the broader assertion that individual cells in normal tissue or a 3D normal-tissue-like culture will respond to radiation very differently than the same cells in a 2D monolayer culture. While many studies have shown that, in some cases, cell-cell contact in spheroids of transformed or tumor cell lines can alter radiation responses relative to those for the same cells in monolayer cultures, a question remains regarding the possible effect of the above-mentioned disruption of signaling networks that operate more specifically for cells in normal tissues or in a 3D tissue-like context. To test the generality of this notion, we used human MCF-10A cells, an immortalized mammary epithelial cell line that produces acinar structures in culture with many properties of human mammary ducts. We compared the dose responses for these cells in the 2D monolayer and in 3D ductal or acinar structures. The responses examined were reproductive cell death, induction of chromosomal aberrations, and the levels of gamma-H2AX foci in cells after single acute gamma-ray doses and immediately after 20 h of irradiation at a dose rate of 0.0017 Gy/min. We found no significant differences in the dose responses of these cells in 2D or 3D growth conditions. While this does not mean that such differences cannot occur in other situations, it does mean that they do not generally or necessarily occur.

  10. Chronic alcohol exposure affects pancreatic acinar mitochondrial thiamin pyrophosphate uptake: studies with mouse 266-6 cell line and primary cells

    PubMed Central

    Srinivasan, Padmanabhan; Nabokina, Svetlana

    2015-01-01

    Thiamin is essential for normal metabolic activity of all mammalian cells, including those of the pancreas. Cells obtain thiamin from their surroundings and enzymatically convert it into thiamin pyrophosphate (TPP) in the cytoplasm; TPP is then taken up by mitochondria via a specific carrier the mitochondrial TPP transporter (MTPPT; product of the SLC25A19 gene). Chronic alcohol exposure negatively impacts the health of pancreatic acinar cells (PAC), but its effect on physiological/molecular parameters of MTPPT is not known. We addressed this issue using mouse pancreatic acinar tumor cell line 266-6 and primary PAC of wild-type and transgenic mice carrying the SLC25A19 promoter that were fed alcohol chronically. Chronic alcohol exposure of 266-6 cells (but not to its nonoxidative metabolites ethyl palmitate and ethyl oleate) led to a significant inhibition in mitochondrial TPP uptake, which was associated with a decreased expression of MTPPT protein, mRNA, and activity of the SLC25A19 promoter. Similarly, chronic alcohol feeding of mice led to a significant inhibition in expression of MTPPT protein, mRNA, heterogeneous nuclear RNA, as well as in activity of SLC25A19 promoter in PAC. While chronic alcohol exposure did not affect DNA methylation of the Slc25a19 promoter, a significant decrease in histone H3 euchromatin markers and an increase in H3 heterochromatin marker were observed. These findings show, for the first time, that chronic alcohol exposure negatively impacts pancreatic MTPPT, and that this effect is exerted, at least in part, at the level of Slc25a19 transcription and appears to involve epigenetic mechanism(s). PMID:26316591

  11. Transdifferentiation of mouse adipose-derived stromal cells into acinar cells of the submandibular gland using a co-culture system

    SciTech Connect

    Lee, Jingu; Park, Sangkyu; Roh, Sangho

    2015-05-15

    A loss of salivary gland function often occurs after radiation therapy in head and neck tumors, though secretion of saliva by the salivary glands is essential for the health and maintenance of the oral environment. Transplantation of salivary acinar cells (ACs), in part, may overcome the side effects of therapy. Here we directly differentiated mouse adipose-derived stromal cells (ADSCs) into ACs using a co-culture system. Multipotent ADSCs can be easily collected from stromal vascular fractions of adipose tissues. The isolated ADSCs showed positive expression of markers such as integrin beta-1 (CD29), cell surface glycoprotein (CD44), endoglin (CD105), and Nanog. The cells were able to differentiate into adipocytes, osteoblasts, and neural-like cells after 14 days in culture. ADSCs at passage 2 were co-cultured with mouse ACs in AC culture medium using the double-chamber (co-culture system) to avoid mixing the cell types. The ADSCs in this co-culture system expressed markers of ACs, such as α-amylases and aquaporin5, in both mRNA and protein. ADSCs cultured in AC-conditioned medium also expressed AC markers. Cellular proliferation and senescence analyses demonstrated that cells in the co-culture group showed lower senescence and a higher proliferation rate than the AC-conditioned medium group at Days 14 and 21. The results above imply direct conversion of ADSCs into ACs under the co-culture system; therefore, ADSCs may be a stem cell source for the therapy for salivary gland damage. - Highlights: • ADSCs could transdifferentiate into acinar cells (ACs) using ACs co-culture (CCA). • Transdifferentiated ADSCs expressed ACs markers such as α-amylase and aquaporin5. • High proliferation and low senescence were presented in CCA at Day 14. • Transdifferentiation of ADSCs into ACs using CCA may be an appropriate method for cell-based therapy.

  12. Effects of the type of dietary fat on acetylcholine-evoked amylase secretion and calcium mobilization in isolated rat pancreatic acinar cells.

    PubMed

    Yago, María D; Díaz, Ricardo J; Martínez, María A; Audi, Nama'a; Naranjo, José A; Martínez-Victoria, Emilio; Mañas, Mariano

    2006-04-01

    Olive oil is a major component of the Mediterranean diet, and its role in human health is being actively debated. This study aimed to clarify the mechanism of pancreatic adaptation to dietary fat. For this purpose, we examined whether dietary-induced modification of pancreatic membranes affects acinar cell function in response to the secretagogue acetylcholine (ACh). Weaning male Wistar rats were assigned to one of two experimental groups and fed for 8 weeks with a commercial chow (C) or a semisynthetic diet containing virgin olive oil as dietary fat (OO). The fatty acid composition of pancreatic plasma membranes was determined by gas-liquid chromatography. For assessment of secretory function, viable acini were incubated with ACh and amylase of supernatant was further assayed with a substrate reagent. Changes in cytosolic Ca(2+) concentration in response to ACh were measured by fura-2 AM fluorimetry. Compared to C rats, pancreatic cell membranes of OO rats had a higher level of monounsaturated fatty acids and a lower level of both saturated and polyunsaturated fatty acids, thus, reflecting the type of dietary fat given. Net amylase secretion in response to ACh was greatly enhanced after OO feeding, although this was not paralleled by enhancement of ACh-evoked Ca(2+) peak increases. In conclusion, chronic intake of diets that differ in the fat type influences not only the fatty acid composition of rat pancreatic membranes but also the responsiveness of acinar cells to ACh. This mechanism may be, at least in part, responsible for the adaptation of the exocrine pancreas to the type of fat available.

  13. Benign tumours affecting the deep lobe of the parotid gland: how to select the optimal surgical approach.

    PubMed

    Casani, A P; Cerchiai, N; Dallan, I; Seccia, V; Sellari Franceschini, S

    2015-04-01

    Many types of approaches allow extra-capsular dissection in the deep parotid parenchyma in the treatment of benign tumours. A transcervical approach (TCA), transparotid approach (TPA) and a combined transcervical-transparotid approach (TPTCA) are the three main procedures performed to expose the deep parenchyma. We conducted a retrospective chart review enrolling 24 consecutive patients treated for benign tumours affecting the deep lobe of the parotid. Review of the surgical data was accompanied by careful follow-up to establish surgical morbidity, functional (Frey's Syndrome and first-bite syndrome) and aesthetical outcomes. A TPA was performed in the majority of cases; in 26% superficial parotidectomy was not required (selective deep parotidectomy). Minor's test showed a low rate of Frey's syndrome (3 cases of 23, 13%). No long-lasting first-bite syndrome was reported. Some additional procedures were easily performed in order to improve aesthetical results (rotational flap of sternocleidomastoid muscle, free abdominal fat transfer); these had the same results as selective deep parotidectomy. TCA (or TPTCA) ensures the best control of the facial nerve, providing good exposure and good functional and aesthetical results (without sparing the superficial parenchyma if additional techniques are performed with the aim of reducing skin depression in the treated area). The choice of the approach should have only the aim of safe resection and should not be influenced by aesthetical outcome; the craniocaudal level of the tumour seems to be the best indicator of the feasibility of the procedure also considering the branches of the facial nerve. In our experience, mandibulotomy can always be avoided.

  14. Evaluation of electrosurgical meniscectomy in rabbits.

    PubMed

    Schosheim, P M; Caspari, R B

    1986-01-01

    Recently, electrosurgical cutting instruments utilizing radiofrequency energy have been designed as arthroscopic devices for cutting meniscal tissue. This study attempted to determine the in vivo gross and microscopic effects of radiofrequency energy on meniscal tissue in rabbits. Twelve adult New Zealand white rabbits (48 menisci) underwent bilateral knee arthrotomies. Ten rabbits (40 menisci) underwent partial meniscectomies in which one half of each meniscus in the longitudinal plane was removed with the electrosurgical generator. Two control rabbits underwent arthrotomy without resection of meniscal tissue. At specific time intervals, the rabbits were killed, and the menisci were removed. The gross specimens were photographed, and microscopic sections of each meniscus were fixed and stained. Specimens were evaluated to determine the cellular and vascular response to the electrosurgical cut edge of each meniscus. The microscopic specimens revealed that the radiofrequency cutting instruments produced a small degree of direct thermal damage to the cut meniscus. A tissue response producing a hypercellular dense collagen matrix was present for approximately 3 months. The spontaneous repair of tissue was complete by 6 months, and the histologic 6-month specimens could not be distinguished from the 6-month control specimens except with respect to the overall width of the specimens.

  15. Hypercholesterolemia Impaired Sperm Functionality in Rabbits

    PubMed Central

    Monclus, Maria A.; Cabrillana, Maria E.; Clementi, Marisa A.; Espínola, Leandro S.; Cid Barría, Jose L.; Vincenti, Amanda E.; Santi, Analia G.; Fornés, Miguel W.

    2010-01-01

    Hypercholesterolemia represents a high risk factor for frequent diseases and it has also been associated with poor semen quality that may lead to male infertility. The aim of this study was to analyze semen and sperm function in diet-induced hypercholesterolemic rabbits. Twelve adult White New Zealand male rabbits were fed ad libitum a control diet or a diet supplemented with 0.05% cholesterol. Rabbits under cholesterol-enriched diet significantly increased total cholesterol level in the serum. Semen examination revealed a significant reduction in semen volume and sperm motility in hypercholesterolemic rabbits (HCR). Sperm cell morphology was seriously affected, displaying primarily a “folded head”-head fold along the major axe-, and the presence of cytoplasmic droplet on sperm flagellum. Cholesterol was particularly increased in acrosomal region when detected by filipin probe. The rise in cholesterol concentration in sperm cells was determined quantitatively by Gas chromatographic-mass spectrometric analyses. We also found a reduction of protein tyrosine phosphorylation in sperm incubated under capacitating conditions from HCR. Interestingly, the addition of Protein Kinase A pathway activators -dibutyryl-cyclic AMP and iso-butylmethylxanthine- to the medium restored sperm capacitation. Finally, it was also reported a significant decrease in the percentage of reacted sperm in the presence of progesterone. In conclusion, our data showed that diet-induced hypercholesterolemia adversely affects semen quality and sperm motility, capacitation and acrosomal reaction in rabbits; probably due to an increase in cellular cholesterol content that alters membrane related events. PMID:20976152

  16. Experimental rabbit models of Chlamydia pneumoniae infection.

    PubMed Central

    Moazed, T. C.; Kuo, C.; Patton, D. L.; Grayston, J. T.; Campbell, L. A.

    1996-01-01

    Chlamydia pneumoniae (TWAR), a common cause of acute respiratory disease in humans, has recently been associated with coronary and aortic atherosclerosis. In this study, we evaluated rabbit models of chlamydial infection to investigate the pathogenesis of C. pneumoniae infection. New Zealand White rabbits were inoculated intranasally and intratracheally with C. pneumoniae, strain AR-39, and primary and repeated infection were assessed. After a single inoculation, lung pathology was characterized by a moderate self-resolving interstitial pneumonia with bronchiolitis of 21 days in duration. Chlamydial DNA was detected by polymerase chain reaction (PCR) intermittently in the upper respiratory tract and lung tissue through day 21 postinoculation, spleen tissue at day 14, and peripheral blood mononuclear cells at days 3 and 21. After repeated inoculations, chlamydial DNA was detected by PCR in the upper respiratory tract and lung tissue through day 42. Lung lesions consisted of multifocal interstitial mononuclear cell aggregates that persisted up to day 42. Watanabe heritable hyperlipidemic rabbits were less susceptible to C. pneumoniae infection. After multiple inoculations of Watanabe rabbits, C. pneumoniae was detected by PCR and/or immunocytochemistry until day 21. In conclusion, C. pneumoniae induced a moderate respiratory infection in these rabbit models. Images Figure 1 Figure 2 Figure 3 PMID:8579129

  17. 9 CFR 354.124 - Quarantine of diseased rabbits.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... shall be dealt with in one of the following ways: (a) If it is determined by a veterinary inspector that... veterinary inspector that further handling of the rabbits will not create a health hazard, such rabbits...

  18. SPF rabbits infected with rabbit hepatitis E virus isolate experimentally showing the chronicity of hepatitis.

    PubMed

    Han, Jian; Lei, Yaxin; Liu, Lin; Liu, Peng; Xia, Junke; Zhang, Yulin; Zeng, Hang; Wang, Lin; Wang, Ling; Zhuang, Hui

    2014-01-01

    This study focused on investigating the pathogenesis seen in specific-pathogen-free (SPF) rabbits following infection with a homologous rabbit HEV isolate (CHN-BJ-rb14) and comparing it to that seen following infection with a heterologous swine genotype 4 HEV isolate (CHN-XJ-SW13). Three of the four animals inoculated with the homologous rabbit HEV became infected, exhibiting an intermittent viremia, obvious fluctuations of liver function biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and persistent fecal virus shedding throughout the nine month study. In addition, liver histopathology showed both chronic inflammation and some degree of fibrosis. Both positive and negative-stranded HEV RNA and HEV antigen expression were detected in liver, brain, stomach, duodenum and kidney from the necropsied rabbits. Inflammation of extrahepatic tissue (duodenum and kidney) was also observed. Three of the four rabbits inoculated with the heterologous genotype 4 swine HEV also became infected, showing similar levels of anti-HEV antibody to that generated following infection with the homologous virus isolate. The duration of both viremia and fecal shedding of virus was however shorter following infection with the heterologous virus and there was no significant elevation of liver function biomarkers. These results suggest that rabbit HEV infection may cause more severe hepatitis and prolong the course of the disease, with a possible chronic trend of hepatitis in SPF rabbits.

  19. Serological Survey for RHD Antibodies in Rabbits from Two Types of Rabbit Breeding Farms.

    PubMed

    Fitzner, A; Niedbalski, W

    2016-09-01

    Seroprevalence studies of RHDV antibodies in domestic rabbits were conducted between 2008-2014. A total of 12,169 sera from the provinces of central, southern and south-east Poland, including 7,570 samples collected from mixed-breed rabbits reared in smallholder farms and nearly 4,600 sera taken mainly from unvaccinated rabbits kept in industrial farms, were examined using ELISA tests. Additionally, cross-reactivity of selected tested and control archival sera using both classic RHDV and RHDVa antigens was determined by HI assay. The overall seroprevalence was 13.3%. In rabbits with unkown history of immunisation or RHD infection which came from small farms, RHDV antibodies were detected in 6.1% ranging between 1.0% to 17.2% of animals. In rabbits of the same group, but with a declared vaccination status, or confirmed exposure to an infectious virus, or coming from exposed females, the seroprevalence ranged from 83% to 100%. Among unvaccinated meat rabbits aged 71 to 90 days from industrial farms, low (1.85%, 4.17%, 11%), medium (34%, 54%) or high rates (98.7%) of seropositivity were detected. The seroconversion recorded in adult vaccinated females from industrial farms was 70% and 95%. Generally, the antibody levels examined by ELISAs and HI were comparable. However, a number of sera from the rabbits from small farms, as well as archival sera, showed clear differences. Several-fold differences in antibody titers, evidenced mainly in the postoutbreak sera, indictaed the contact of animals with RHDVa antigen. The overall results of the survey revealed a great proportion of seronegative rabbits potentially highly susceptible to RHD infection. In combination with the emergence of a novel pathogenic RHD virus type (RHDV2), it poses a severe risk of a next wave of fatal disease cases spreading in the native population of domestic rabbits, especially in farms with a traditional system of husbandry.

  20. Pathogenic microbes isolated from rabbit urine.

    PubMed

    Akinboade, O A; Adegoke, G O; Ogunji, F O; Nwufoh, K J

    1981-07-01

    Asymptomatic urinary tract infections were recovered from the urine of 40 of 100 rabbits, and identical bacteria were isolated when the rabbits were retested. Urine samples which yielded significant growths of bacteria also had pus cells. Some specimens yielded more than 2 different isolates, and staphylococci were the most frequently isolated bacteria. Oxalate and uric acid crystals were seen in 6% of the samples, particularly those with significant growths of Pseudomonas aeruginosa. No ova, parasites or fungal elements were seen in 'wet-mount' preparations and no fungi were seen when urine samples were cultured. Female rabbits showed a higher number of bacterial isolates than males. Animals with significant isolates were treated with suitable antibiotics and repeat samples yielded no growth.

  1. Light stimulation of iris tyrosinase in vivo. [Rabbits

    SciTech Connect

    Dryja, T.P.; Kimball, G.P.; Albert, D.M.

    1980-05-01

    This paper presents evidence that light stimulates tyrosinase activity in iris melanocytes in rabbits. Levels of iris tyrosinase were found to be greater in eyes of rabbits exposed to light for 6 weeks than in eyes of rabbits maintained in darkness. Despite increasing tyrosinase levels, exposure to light produced no clinically observable change in iris color.

  2. Comparative quantitative monitoring of rabbit haemorrhagic disease viruses in rabbit kittens

    PubMed Central

    2014-01-01

    Background Only one strain (the Czech CAPM-v351) of rabbit haemorrhagic disease virus (RHDV) has been released in Australia and New Zealand to control pest populations of the European rabbit O. cuniculus. Antigenic variants of RHDV known as RHDVa strains are reportedly replacing RHDV strains in other parts of the world, and Australia is currently investigating the usefulness of RHDVa to complement rabbit biocontrol efforts in Australia and New Zealand. RHDV efficiently kills adult rabbits but not rabbit kittens, which are more resistant to RHD the younger they are and which may carry the virus without signs of disease for prolonged periods. These different infection patterns in young rabbits may significantly influence RHDV epidemiology in the field and hence attempts to control rabbit numbers. Methods We quantified RHDV replication and shedding in 4–5 week old rabbits using quantitative real time PCR to assess their potential to shape RHDV epidemiology by shedding and transmitting virus. We further compared RHDV-v351 with an antigenic variant strain of RHDVa in kittens that is currently being considered as a potential RHDV strain for future release to improve rabbit biocontrol in Australia. Results Kittens were susceptible to infection with virus doses as low as 10 ID50. Virus growth, shedding and transmission after RHDVa infection was found to be comparable or non-significantly lower compared to RHDV. Virus replication and shedding was observed in all kittens infected, but was low in comparison to adult rabbits. Both viruses were shed and transmitted to bystander rabbits. While blood titres indicated that 4–5 week old kittens mostly clear the infection even in the absence of maternal antibodies, virus titres in liver, spleen and mesenteric lymph node were still high on day 5 post infection. Conclusions Rabbit kittens are susceptible to infection with very low doses of RHDV, and can transmit virus before they seroconvert. They may therefore play an important

  3. The Genetic Structure of Domestic Rabbits

    PubMed Central

    Carneiro, Miguel; Afonso, Sandra; Geraldes, Armando; Garreau, Hervé; Bolet, Gerard; Boucher, Samuel; Tircazes, Aurélie; Queney, Guillaume; Nachman, Michael W.; Ferrand, Nuno

    2011-01-01

    Understanding the genetic structure of domestic species provides a window into the process of domestication and motivates the design of studies aimed at making links between genotype and phenotype. Rabbits exhibit exceptional phenotypic diversity, are of great commercial value, and serve as important animal models in biomedical research. Here, we provide the first comprehensive survey of nucleotide polymorphism and linkage disequilibrium (LD) within and among rabbit breeds. We resequenced 16 genomic regions in population samples of both wild and domestic rabbits and additional 35 fragments in 150 rabbits representing six commonly used breeds. Patterns of genetic variation suggest a single origin of domestication in wild populations from France, supporting historical records that place rabbit domestication in French monasteries. Levels of nucleotide diversity both within and among breeds were ∼0.2%, but only 60% of the diversity present in wild populations from France was captured by domestic rabbits. Despite the recent origin of most breeds, levels of population differentiation were high (FST = 17.9%), but the majority of polymorphisms were shared and thus transferable among breeds. Coalescent simulations suggest that domestication began with a small founding population of less than 1,200 individuals. Taking into account the complex demographic history of domestication with two successive bottlenecks, two loci showed deviations that were consistent with artificial selection, including GPC4, which is known to be associated with growth rates in humans. Levels of diversity were not significantly different between autosomal and X-linked loci, providing no evidence for differential contributions of males and females to the domesticated gene pool. The structure of LD differed substantially within and among breeds. Within breeds, LD extends over large genomic distances. Markers separated by 400 kb typically showed r2 higher than 0.2, and some LD extended up to 3,200 kb

  4. Rabbits and hominin survival in Iberia.

    PubMed

    Fa, John E; Stewart, John R; Lloveras, Lluís; Vargas, J Mario

    2013-04-01

    High dependence on the hunting and consumption of large mammals by some hominins may have limited their survival once their preferred quarry became scarce or disappeared. Adaptation to smaller residual prey would have been essential after the many large-bodied species decreased in numbers. We focus on the use of a superabundant species, the rabbit, to demonstrate the importance of this taxon in Iberia as fundamental to predators. We show that the use of the rabbit over time has increased, and that there could have been differential consumption by Neanderthals and Anatomically Modern Humans (AMH). Analysis of bone remains from excavations throughout Iberia show that this lagomorph was a crucial part of the diet of AMH but was relatively unutilised during the Mousterian, when Neanderthals were present. We first present changes in mammalian biomass and mean body mass of mammals over 50,000 years, to illustrate the dramatic loss of large mammalian fauna and to show how the rabbit may have contributed a consistently high proportion of the available game biomass throughout that period. Unlike the Italian Peninsula and other parts of Europe, in Iberia the rabbit has provided a food resource of great importance for predators including hominins. We suggest that hunters that could shift focus to rabbits and other smaller residual fauna, once larger-bodied species decreased in numbers, would have been able to persist. From the evidence presented here, we postulate that Neanderthals may have been less capable of prey-shifting and hence use the high-biomass prey resource provided by the rabbit, to the extent AMH did.

  5. Experimental infection of wild-caught European rabbits (Oryctolagus cuniculus) with Sarcoptes scabiei from a naturally infected wild rabbit.

    PubMed

    Millán, J; Casais, R; Colomar, V; Bach, E; Prieto, J M; Velarde, R

    2013-06-01

    Scabies was recently reported for the first time in the European wild rabbit, Oryctolagus cuniculus (Lagomorpha: Leporidae). We experimentally exposed 10 seronegative wild-caught rabbits to skin from a mangy wild rabbit. Serological, physiological, parasitological and histopathological changes were recorded. Three rabbits developed antibodies at 2-5 weeks post-infection (w.p.i.), two of which then developed lesions at 7 w.p.i. One of these had a small area of alopecia on the hind limb that healed naturally within 1 week; the other developed more extensive lesions restricted to the hind limbs (as typically observed in wild rabbits) that lasted until the rabbit died (12.5 w.p.i.). The third rabbit died of trauma 5 w.p.i. before developing any lesions. Antibodies in the healed rabbit disappeared from serum at 8 w.p.i., whereas antibody levels in the sick rabbit increased until its death. Disseminated intravascular coagulation and hepatic necrosis, probably arising from a concomitant infection with rabbit haemorrhagic disease virus, were the likely final cause of death in this rabbit. The mangy rabbit that served as a donor died of a multifocal fibrinosuppurative pneumonia that may have been secondary to the skin bacterial pyoderma.

  6. Cloning, Characteristics, and Functional Analysis of Rabbit NADPH Oxidase 5

    PubMed Central

    Chen, Feng; Yin, Caiyong; Dimitropoulou, Christiana; Fulton, David J. R.

    2016-01-01

    Background: Nox5 was the last member of the Nox enzyme family to be identified. Functionally distinct from the other Nox isoforms, our understanding of its physiological significance has been hampered by the absence of Nox5 in mouse and rat genomes. Nox5 is present in the genomes of other species such as the rabbit that have broad utility as models of cardiovascular disease. However, the mRNA sequence, characteristics, and functional analysis of rabbit Nox5 has not been fully defined and were the goals of the current study. Methods: Rabbit Nox5 was amplified from rabbit tissue, cloned, and sequenced. COS-7 cells were employed for expression and functional analysis via Western blotting and measurements of superoxide. We designed and synthesized miRNAs selectively targeting rabbit Nox5. The nucleotide and