The Experts below are selected from a list of 13185 Experts worldwide ranked by ideXlab platform
Asif Rashid - One of the best experts on this subject based on the ideXlab platform.
-
Goblet Cell carcinoid tumor mixed Goblet Cell carcinoid adenocarcinoma and adenocarcinoma of the appendix comparison of clinicopathologic features and prognosis
Archives of Pathology & Laboratory Medicine, 2015Co-Authors: Melissa W Taggart, Susan C Abraham, Michael J Overman, Paul F Mansfield, Asif RashidAbstract:Context.— The prognosis of appendiceal Goblet Cell carcinoid tumors (GCTs) is believed to be intermediate between appendiceal adenocarcinomas and conventional carcinoid tumors. However, GCTs can have mixed morphologic patterns, with variable amount of adenocarcinoma. Objective.— To evaluate the behavior of GCTs and related entities with variable components of adenocarcinoma. Design.— We classified 74 cases of appendiceal tumors into 3 groups: group 1, GCTs or GCTs with less than 25% adenocarcinoma; group 2, GCTs with 25% to 50% adenocarcinoma; group 3, GCTs with more than 50% adenocarcinoma; and a comparison group of 68 adenocarcinomas without a GCT component (group 4). Well-differentiated mucinous adenocarcinomas were excluded. Clinicopathologic features and follow-up were obtained from computerized medical records and the US Social Security Death Index. Results.— Of the 142 tumors studied, 23 tumors (16%) were classified as group 1; 27 (19%) as group 2; 24 (17%) as group 3; and 68 (48%) as group 4. Stag...
-
genetic alterations in Goblet Cell carcinoids of the vermiform appendix and comparison with gastrointestinal carcinoid tumors
Modern Pathology, 2003Co-Authors: Mirela Stancu, Charita Wallace, Patrick S Houlihan, Tsung Teh Wu, Stanley R Hamilton, Asif RashidAbstract:Genetic Alterations in Goblet Cell Carcinoids of the Vermiform Appendix and Comparison with Gastrointestinal Carcinoid Tumors
-
Genetic Alterations in Goblet Cell Carcinoids of the Vermiform Appendix and Comparison with Gastrointestinal Carcinoid Tumors
Modern Pathology, 2003Co-Authors: Mirela Stancu, Charita Wallace, Patrick S Houlihan, Tsung Teh Wu, Stanley R Hamilton, Asif RashidAbstract:Goblet Cell carcinoid is a relatively rare neuroendocrine tumor of the vermiform appendix with poorly understood molecular pathogenesis. We studied the clinicopathologic features and genetic alterations, including allelic loss of chromosomes 11q, 16q, and 18q; sequencing of the K-ras , β-catenin, and DPC4 ( SMAD4 ) genes; and p53 overexpression and loss of DPC4 by immunohistochemistry; in 16 Goblet Cell carcinoids. We compared the allelic loss in Goblet Cell carcinoids to those in 18 gastrointestinal carcinoid tumors. For Goblet Cell carcinoids, appendiceal perforation was the most common (70%, 7/10) clinical presentation. The mean tumor size was 2.0 ± 1.5 cm (range, 0.4 to 4.5 cm). The tumor invaded to appendiceal serosa in 50% (8/16) of patients, and two patients had metastasis in lymph nodes or adjoining viscera. With mean follow-up of 24 ± 14 months (median, 23 mo), 1 of 10 patients had died of disease, and 2 others had tumor recurrence. All four patients with metastases, recurrences, and/or death from disease had serosal involvement at presentation ( P = .02). Loss of heterozygosity of chromosome 11q was present in 25% of Goblet Cell carcinoids, 14% of ileal carcinoid tumors, and 9% of nonileal carcinoid tumors; of chromosome 16q in 38%, 29%, and 0 ( P = .02); and of chromosome 18q in 56%, 86%, and 9% ( P = .002), respectively. No mutations of K-ras , β-catenin, or DPC4 genes; p53 overexpression; or loss of staining for DPC4 was present in any tumors. These findings suggest that allelic loss of chromosomes 11q, 16q, and 18q in Goblet Cell carcinoids and ileal carcinoids may have an important role in the pathogenesis of these tumors.
Darlene A Dartt - One of the best experts on this subject based on the ideXlab platform.
-
context dependent regulation of conjunctival Goblet Cell function by allergic mediators
Scientific Reports, 2018Co-Authors: Darlene A Dartt, Laura Garciaposadas, Robin R Hodges, Yolanda DieboldAbstract:In the eye, Goblet Cells responsible for secreting mucins are found in the conjunctiva. When mucin production is not tightly regulated several ocular surface disorders may occur. In this study, the effect of the T helper (Th) 2-type cytokines IL4, IL5, and IL13 on conjunctival Goblet Cell function was explored. Goblet Cells from rat conjunctiva were cultured and characterized. The presence of cytokine receptors was confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Changes in intraCellular [Ca2+], high molecular weight glycoconjugate secretion, and proliferation were measured after stimulation with Th2 cytokines with or without the allergic mediator histamine. We found that IL4 and IL13 enhance Cell proliferation and, along with histamine, stimulate Goblet Cell secretion. We conclude that the high levels of IL4, IL5, and IL13 that characterize allergic conjunctivitis could be the reason for higher numbers of Goblet Cells and mucin overproduction found in this condition.
-
effect of tear hyperosmolarity and signs of clinical ocular surface pathology upon conjunctival Goblet Cell function in the human ocular surface
Investigative Ophthalmology & Visual Science, 2011Co-Authors: Jonathan E Moore, Gilbert T Vasey, Darlene A Dartt, Victoria Mcgilligan, Sarah D Atkinson, Claire Grills, P J Lamey, Antonio LeccisottiAbstract:PURPOSE To investigate the effect of tear hyperosmolarity and signs of clinical ocular surface pathology on conjunctival Goblet Cell population. METHODS 111 participants were assessed using tear osmolarity (TO) measurements and a comprehensive selection of clinical ophthalmic tests. The resultant clinical database was assessed for evidence of patterns of composite increasing pathology. The total, filled, and empty Goblet Cell numbers were measured: total number of Goblet Cells as per cytokeratin 7 (CK7) immunofluorescence and number of filled Goblet Cells as per periodic acid Schiff's reagent (PAS) or lectin helix pomatia agglutinin (HPA). Goblet Cell profile was correlated with composite clinical pathologic grades. RESULTS No significant correlation was found between TO and Goblet Cell number or function (as indicated by number of filled or unfilled Goblet Cells). Distinct composite clinical pathologic groups 0-IV with increasing pathology were created based on the frequency of positive pathologic signs, which adhered to the Dry Eye Workshop purported mechanism. Only in group IV was there significantly increased mean tear osmolarity of 344 mOsm/L (P < 0.000) along with significantly decreased empty Goblet Cell number (CK7+ and HPA-) compared to filled (CK7+ and HPA+, P = 0.000). When the number of filled Goblet Cells (PAS+) was analyzed there was significant increase in tear osmolarity for the two most severe grades; 3 and 4. CONCLUSIONS The Goblet Cell population does not appear to be affected by isolated tear hyperosmolarity. Hyperosmolarity when combined with other ocular surface pathology or inflammation alters the Goblet Cell population.
-
conjunctival Goblet Cell secretion stimulated by leukotrienes is reduced by resolvins d1 and e1 to promote resolution of inflammation
Journal of Immunology, 2011Co-Authors: Darlene A Dartt, Robin R Hodges, Marie A Shatos, Kameran Lashkari, Charles N SerhanAbstract:The conjunctiva is a mucous membrane that covers the sclera and lines the inside of the eyelids. Throughout the conjunctiva are Goblet Cells that secrete mucins to protect the eye. Chronic inflammatory diseases such as allergic conjunctivitis and early dry eye lead to increased Goblet Cell mucin secretion into tears and ocular surface disease. The purpose of this study was to determine the actions of the inflammatory mediators, the leukotrienes and the proresolution resolvins, on secretion from cultured rat and human conjunctival Goblet Cells. We found that both cysteinyl leukotriene (CysLT) receptors, CysLT1 and CysLT2, were present in rat conjunctiva and in rat and human cultured conjunctival Goblet Cells. All leukotrienes LTB4, LTC4, LTD4, and LTE4, as well as PGD2, stimulated Goblet Cell secretion in rat Goblet Cells. LTD4 and LTE4 increased the intraCellular Ca2+ concentration ([Ca2+]i), and LTD4 activated ERK1/2. The CysLT1 receptor antagonist MK571 significantly decreased LTD4-stimulated rat Goblet Cell secretion and the increase in [Ca2+]i. Resolvins D1 (RvD1) and E1 (RvE1) completely reduced LTD4-stimulated Goblet Cell secretion in cultured rat Goblet Cells. LTD4-induced secretion from human Goblet Cells was blocked by RvD1. RvD1 and RvE1 prevented LTD4- and LTE4-stimulated increases in [Ca2+]i, as well as LTD4 activation of ERK1/2. We conclude that cysteinyl leukotrienes stimulate conjunctival Goblet Cell mucous secretion with LTD4 using the CysLT1 receptor. Stimulated secretion is terminated by preventing the increase in [Ca2+]i and activation of ERK1/2 by RvD1 and RvE1.
-
role of mitogen activated protein kinase in cholinergic stimulation of conjunctival Goblet Cell secretion
Advances in Experimental Medicine and Biology, 2002Co-Authors: Darlene A Dartt, Jose D Rios, Harumi Kanno, Driss ZoukhriAbstract:Conjunctival Goblet Cells are a primary source for the mucous layer of the tear film. We showed previously that conjunctival Goblet Cell mucin secretion is under neural control as activation of afferent sensory nerves in the cornea stimulates mucin secretion.1 This neural reflex is mediated either by the parasympathetic and sympathetic nerves that surround the Goblet Cells, or by antidromic stimulation of the sensory nerves in the conjunctiva and collateral sensory nerves from the cornea. Exogenous addition of the parasympathetic agonist carbachol or the parasympathetic neuropeptide VIP stimulated conjunctival Goblet Cell secretion.2,3 Cholinergic agonists released from parasympathetic nerves bind to and activate G protein linked- M2 and M3 muscarinic receptors. In most tissues, activation of these receptors stimulates phospholipase C to hydrolyze phosphatidylinositol 4,5-bisphosphate into inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). IP3 binds to specific receptors on the endoplasmic reticulum to increase intraCellular Ca2+. The increased intraCellular Ca2+ either directly, or in combination with Ca2+/calmodulin-dependent protein kinases, activates mucin secretion. DAG in turn stimulates protein kinase C (PKC). In many tissues, cholinergic agonists also activate the mitogen-activated protein kinase (MAPK) signaling pathway used by growth factor receptors, which usually regulate Cell growth and proliferation. Activation of the MAPK pathway by cholinergic agonists can occur through several mechanisms. One such mechanism is through transactivation of the EGF receptor in an EGF-independent manner.4 The activated recepter then serves as a scaffold for recruitment of Grb2-SoS complex via tyrosine phosphorylation of Shc.
-
immunolocalization of muscarinic and vip receptor subtypes and their role in stimulating Goblet Cell secretion
Investigative Ophthalmology & Visual Science, 1999Co-Authors: Jose D Rios, Robin R Hodges, James D Zieske, Driss Zoukhri, Ian Rawe, Darlene A DarttAbstract:PURPOSE. TO determine the subtypes of cholinergic muscarinic receptors and receptors for vasoactive intestinal peptide (VIP) present in rat conjunctival Goblet Cells and whether cholinergic agonists and VIP stimulate Goblet Cell secretion. METHODS. Immunofluorescence studies were performed using antibodies against the m1( m2, and m3 muscarinic receptor subtypes and VIP receptors 1 and 2 (VIPR1 and VIPR2). The lectin Ulex europeus agglutinin I was used to measure glycoconjugate secretion, the index of secretion, from Goblet Cells in an enzyme-linked lectin assay. In this assay, pieces of conjunctiva were placed on filter paper and incubated for 15 to 120 minutes, with or without increasing concentrations of the cholinergic agonist carbachol or VIP. The muscarinic antagonist atropine and the muscarinic receptor-subtype-selective antagonists pirenzepine (M,), gallamine (M2), and 4-4-diphenylacetoxy-7V-(2-chloroethyl)-piperidine hydrochloride (4-DAMP mustard; M3) were incubated with carbachol to determine specificity of receptor activation. RESULTS. Immunoreactivity to M2 and M3 receptors was found on Goblet Cell membranes subjacent to the secretory granules. Immunoreactivity to M, receptor was not on Goblet Cells but was on the stratified squamous Cells. Immunoreactivity to VIPR2 was found on Goblet Cells with a localization similar to that of the M2 and M3 receptors. VIPR1 was not found on Goblet Cells or on the stratified squamous Cells. Carbachol and VIP induced a time- and concentration-dependent stimulation of glycoconjugate secretion. Carbachol, at 10~ 4 M, induced a threefold increase in glycoconjugate secretion, which was completely inhibited by atropine (10~ 5 M). Carbachol-induced secretion was inhibited 54% ± 8% by pirenzepine (1CT 5 M), 69% ± 14% by gallamine (10~ 5 M), and 72% ± 11% by 4-DAMP mustard (10~ 5 M). A twofold increase in glycoconjugate secretion was obtained with VIP at 10~ 8 M. CONCLUSIONS. Cholinergic agonists, through M2 and/or M3 muscarinic receptors, and VIP, through VIPR2, regulate conjunctival Goblet Cell secretion, suggesting that Goblet Cell secretion in vivo is under the control of parasympathetic nerves. (Invest Ophthalmol Vis Sci. 1999;40:1102-1 111)
Atsushi Nagai - One of the best experts on this subject based on the ideXlab platform.
-
niflumic acid inhibits Goblet Cell degranulation in a guinea pig asthma model
Allergology International, 2012Co-Authors: Mitsuko Kondo, Jun Tamaoki, Kiyoshi Takeyama, Junko Nakata, Naoki Arai, Takehiro Izumo, Etsuko Tagaya, Atsushi NagaiAbstract:ABSTRACT Background: Human Ca 2+ -activated Cl ion channel 1 (hCLCAl) is expressed in Goblet Cell hyperplasia in the airway of asthmatics, and murine CLCA3 is associated with antigen-sensitized and IL-13-induced Goblet Cell metaplasia in mice. However, the role of CLCA in Goblet Cell degranulation is not fully investigated. Niflumic acid (NFA), a relatively specific CLCA inhibitor, inhibits Goblet Cell metaplasia, but the effect of NFA on Goblet Cell degranulation has not been determined in an asthma model. Methods: Guinea pigs were sensitized with ovalbumin (OA) twice and then challenged with saline, OA, histamine, and one of the Ca 2+- dependent secretagogues, UTP. The PAS/AB-stained mucus area in the tracheal epithelium was measured with a computer image analysis system, and the morphology of mucus granules was examined by transmission electron microscopy. In the in vitro experiment, Goblet Cells cultured with IL-13 at the air-liquid interface were stimulated with UTP in the presence or absence of NFA, and the MUC5AC level in Cell lysates was measured by ELISA. Results: The mucus areas were smaller in the OA-, histamine-, and UTP-challenged animals than in the saline-challenged animals. NFA inhibited the decrease in mucus area and morphological changes in mucus granules. UTP caused swelling and exocytosis of mucus granules and MUC5AC secretion by cultured Goblet Cells, and NFA inhibited these changes. Conclusions: NFA inhibited the secretory response of mucus granules in an asthma model, suggesting that CLCA may be associated with Goblet Cell degranulation and that CLCA inhibitors may be useful for the treatment of hypersecretion in asthma.
-
interleukin 13 induces Goblet Cell differentiation in primary Cell culture from guinea pig tracheal epithelium
American Journal of Respiratory Cell and Molecular Biology, 2002Co-Authors: Mitsuko Kondo, Jun Tamaoki, Kiyoshi Takeyama, Junko Nakata, Atsushi NagaiAbstract:The Th2 cytokines, interleukin (IL)-4 and IL-13, bind to IL-4R, that IL-4 inhibited mucus secretion and attenuated the gene and cause Goblet Cell metaplasia/hyperplasia with increased expression of MUC5AC and MUC5B in primary human mucin expression in vivo. However, there is not enough evi- bronchial epithelial Cells (8), and that IL-4 did not induce dence that these cytokines directly induce mucin production in MUC5AC gene expression in mucoepidermoid carcinoma vitro. In this study, primary epithelial Cells from guinea pig Cell line, NCI-H292 (9). Concerning IL-13, Longphre and cotrachea were cultured at an air–liquid interface, and immedi- workers (10) reported that IL-13 did not increase MUC5AC ately after achieving confluence at Day 7 they were treated gene expression in NCI-H292 Cells, but it is uncertain with human recombinant IL-4 or IL-13 for 14 d. IL-13–treated whether IL-13 induces mucin production and MUC5AC Cells consisted of a large number of fully mature Goblet Cells expression in primary culture of lower airway epithelium. with a smaller number of ciliated Cells. Secretory granules of the Goblet Cells were positive for both periodic acid-Schiff and We studied the effects of IL-4 and IL-13 on airway epitoluidine blue, and showed exocytosis. By contrast, IL-4 failed thelial differentiation using air–liquid interface culture, a to induce Goblet Cell differentiation. The electric resistances of procedure that induces high levels of differentiation (11–13), IL-13–treated Cells were lower than those of IL-4–treated Cells with airway epithelial Cells differentiating into both ciliated and nontreated Cells, suggesting leaky epithelia. MUC5AC pro- and Goblet Cells. In this study, we focused on the numbers of tein level in Cell lysates measured by ELISA was several-fold Goblet Cells and ciliated Cells, because Goblet Cell hyperplasia higher in IL-13–treated Cells than in nontreated Cells, whereas along with correspondingly fewer ciliated Cells may cause the level in IL-4–treated Cells was not changed. These data the impairment of mucociliary clearance that is found in suggest that human recombinant IL-13, but not IL-4, can induce the airways of patients who die of asthma (14). We also
Mirela Stancu - One of the best experts on this subject based on the ideXlab platform.
-
genetic alterations in Goblet Cell carcinoids of the vermiform appendix and comparison with gastrointestinal carcinoid tumors
Modern Pathology, 2003Co-Authors: Mirela Stancu, Charita Wallace, Patrick S Houlihan, Tsung Teh Wu, Stanley R Hamilton, Asif RashidAbstract:Genetic Alterations in Goblet Cell Carcinoids of the Vermiform Appendix and Comparison with Gastrointestinal Carcinoid Tumors
-
Genetic Alterations in Goblet Cell Carcinoids of the Vermiform Appendix and Comparison with Gastrointestinal Carcinoid Tumors
Modern Pathology, 2003Co-Authors: Mirela Stancu, Charita Wallace, Patrick S Houlihan, Tsung Teh Wu, Stanley R Hamilton, Asif RashidAbstract:Goblet Cell carcinoid is a relatively rare neuroendocrine tumor of the vermiform appendix with poorly understood molecular pathogenesis. We studied the clinicopathologic features and genetic alterations, including allelic loss of chromosomes 11q, 16q, and 18q; sequencing of the K-ras , β-catenin, and DPC4 ( SMAD4 ) genes; and p53 overexpression and loss of DPC4 by immunohistochemistry; in 16 Goblet Cell carcinoids. We compared the allelic loss in Goblet Cell carcinoids to those in 18 gastrointestinal carcinoid tumors. For Goblet Cell carcinoids, appendiceal perforation was the most common (70%, 7/10) clinical presentation. The mean tumor size was 2.0 ± 1.5 cm (range, 0.4 to 4.5 cm). The tumor invaded to appendiceal serosa in 50% (8/16) of patients, and two patients had metastasis in lymph nodes or adjoining viscera. With mean follow-up of 24 ± 14 months (median, 23 mo), 1 of 10 patients had died of disease, and 2 others had tumor recurrence. All four patients with metastases, recurrences, and/or death from disease had serosal involvement at presentation ( P = .02). Loss of heterozygosity of chromosome 11q was present in 25% of Goblet Cell carcinoids, 14% of ileal carcinoid tumors, and 9% of nonileal carcinoid tumors; of chromosome 16q in 38%, 29%, and 0 ( P = .02); and of chromosome 18q in 56%, 86%, and 9% ( P = .002), respectively. No mutations of K-ras , β-catenin, or DPC4 genes; p53 overexpression; or loss of staining for DPC4 was present in any tumors. These findings suggest that allelic loss of chromosomes 11q, 16q, and 18q in Goblet Cell carcinoids and ileal carcinoids may have an important role in the pathogenesis of these tumors.
Koichiro Matsumoto - One of the best experts on this subject based on the ideXlab platform.
-
differential regulation by glucocorticoid of interleukin 13 induced eosinophilia hyperresponsiveness and Goblet Cell hyperplasia in mouse airways
American Journal of Respiratory and Critical Care Medicine, 2003Co-Authors: Atsuko Kibe, Hiromasa Inoue, Satoru Fukuyama, Kentaro Machida, Koichiro MatsumotoAbstract:Interleukin (IL)-13 induces important features of bronchial asthma such as eosinophilic infiltration, airway hyperresponsiveness (AHR), and mucus hypersecretion. Although glucocorticoids suppress airway inflammation and remain the most effective therapy for asthma, the effects of glucocorticoids on the IL-13–dependent features are unknown. We studied the effects of dexamethasone on eotaxin production, eosinophil accumulation, Goblet Cell hyperplasia, and AHR after IL-13 administration into the airways of mice in vivo. MUC5AC gene expression, a marker of Goblet Cell hyperplasia, was also analyzed. IL-13 alone dose dependently induced AHR. Treatment with dexamethasone inhibited eotaxin expression and completely abolished eosinophil accumulation, but it did not affect AHR, MUC5AC overexpression, or Goblet Cell hyperplasia induced by IL-13. The effects of tumor necrosis factor-α on IL-13–induced AHR were also examined. Tumor necrosis factor-α did not affect AHR despite marked enhancement of eosinophil infiltr...
