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University of Manchester

1. Davies, Heather. Mucins in the alimentary canal : their structure and interactions with polyphenols.

Degree: PhD, 2014, University of Manchester

The polymeric gel-forming mucins provide the structural framework of saliva and the mucus barriers that cover the mucosal surfaces of the alimentary canal. Dietary compounds may influence the barrier properties of these protective layers. The effects of green tea polyphenols, which have many health benefits but have low bioavailability and contribute to the astringency of green tea, on the structural properties of the mucins in the alimentary canal are investigated here. Using well characterised, highly purified salivary mucins MUC5B and MUC7, and porcine gastric mucins, the effects of the green tea polyphenol epigallocatechin-3-gallate (EGCG) on mucins were studied here. Using rate-zonal centrifugation coupled to agarose gel electrophoresis, atomic force microscopy and particle tracking microrheology, EGCG, at concentrations found in a cup of green tea, caused increased aggregation of MUC5B in human whole saliva, and increased aggregation and viscosity of purified MUC5B. It was revealed using recombinant proteins of the N- and C-terminal regions of MUC5B that EGCG had these effects by aggregating the terminal globular protein domains of MUC5B. In contrast, MUC5B trypsin-resistant high molecular weight glycopeptides were not aggregated by EGCG, demonstrating that the oligosaccharide-rich, highly-glycosylated regions of mucins are not involved in the EGCG-induced aggregation of mucins. EGCG also caused the majority of MUC7 in human whole saliva to aggregate, and purified MUC7 also showed substantial aggregation in the presence of EGCG.Porcine gastric mucins were also used in order to model human gastric mucins. First, the identity of the porcine gastric mucins was explored using tandem mass spectrometry and immunohistochemistry. This revealed that Muc5ac was expressed by the surface epithelium and was the prominent mucin in porcine gastric mucus. Muc6 was expressed by gastric submucosal glands, but was not a major component of the secreted mucus barrier. Porcine Muc5ac and Muc6 were shown to be aggregated by EGCG. These data demonstrate that mucins from both saliva and the stomach are substantially altered by EGCG. This may contribute to the astringency and low bioavailability of EGCG. In contrast, the green tea polyphenol epicatechin (EC) did not cause aggregation of salivary mucins or porcine gastric mucins, suggesting that the galloyl ring of EGCG (which is absent in EC) is important for its aggregation of mucins, and that EC has different mechanisms of astringency. The structure of the mucins in the alimentary canal was studied using Raman spectroscopy, Raman optical activity (ROA) and Tip-enhanced Raman spectroscopy (TERS). The secondary structure of the oligosaccharide-rich regions of mucins was shown to be largely disordered, with some contribution of poly-proline II helix. The N- and C-terminal regions of MUC5B were largely β-sheet in structure, with some disordered structure also present in the C-terminal region. Raman spectroscopy could reliably distinguish between MUC5B glycoforms, demonstrating the…

Subjects/Keywords: 572; Mucin; Stomach; Mucus; Saliva; MUC5B; MUC7; Muc5ac; Muc6; Green tea polyphenols; Epigallocatechin-3-gallate; EGCG; Raman spectroscopy; Raman optical activity; Tip-enhanced Raman spectroscopy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Davies, H. (2014). Mucins in the alimentary canal : their structure and interactions with polyphenols. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/mucins-in-the-alimentary-canal-their-structure-and-interactions-with-polyphenols(76aaa531-bf78-4be1-94a7-c8b4db9114bb).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.677729

Chicago Manual of Style (16th Edition):

Davies, Heather. “Mucins in the alimentary canal : their structure and interactions with polyphenols.” 2014. Doctoral Dissertation, University of Manchester. Accessed September 21, 2020. https://www.research.manchester.ac.uk/portal/en/theses/mucins-in-the-alimentary-canal-their-structure-and-interactions-with-polyphenols(76aaa531-bf78-4be1-94a7-c8b4db9114bb).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.677729.

MLA Handbook (7th Edition):

Davies, Heather. “Mucins in the alimentary canal : their structure and interactions with polyphenols.” 2014. Web. 21 Sep 2020.

Vancouver:

Davies H. Mucins in the alimentary canal : their structure and interactions with polyphenols. [Internet] [Doctoral dissertation]. University of Manchester; 2014. [cited 2020 Sep 21]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/mucins-in-the-alimentary-canal-their-structure-and-interactions-with-polyphenols(76aaa531-bf78-4be1-94a7-c8b4db9114bb).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.677729.

Council of Science Editors:

Davies H. Mucins in the alimentary canal : their structure and interactions with polyphenols. [Doctoral Dissertation]. University of Manchester; 2014. Available from: https://www.research.manchester.ac.uk/portal/en/theses/mucins-in-the-alimentary-canal-their-structure-and-interactions-with-polyphenols(76aaa531-bf78-4be1-94a7-c8b4db9114bb).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.677729

2. Davies, Heather. Mucins in the alimentary canal: their structure and interactions with polyphenols.

Degree: 2014, University of Manchester

The polymeric gel-forming mucins provide the structural framework of saliva and the mucus barriers that cover the mucosal surfaces of the alimentary canal. Dietary compounds may influence the barrier properties of these protective layers. The effects of green tea polyphenols, which have many health benefits but have low bioavailability and contribute to the astringency of green tea, on the structural properties of the mucins in the alimentary canal are investigated here. Using well characterised, highly purified salivary mucins MUC5B and MUC7, and porcine gastric mucins, the effects of the green tea polyphenol epigallocatechin-3-gallate (EGCG) on mucins were studied here.Using rate-zonal centrifugation coupled to agarose gel electrophoresis, atomic force microscopy and particle tracking microrheology, EGCG, at concentrations found in a cup of green tea, caused increased aggregation of MUC5B in human whole saliva, and increased aggregation and viscosity of purified MUC5B. It was revealed using recombinant proteins of the N- and C-terminal regions of MUC5B that EGCG had these effects by aggregating the terminal globular protein domains of MUC5B. In contrast, MUC5B trypsin-resistant high molecular weight glycopeptides were not aggregated by EGCG, demonstrating that the oligosaccharide-rich, highly-glycosylated regions of mucins are not involved in the EGCG-induced aggregation of mucins. EGCG also caused the majority of MUC7 in human whole saliva to aggregate, and purified MUC7 also showed substantial aggregation in the presence of EGCG.Porcine gastric mucins were also used in order to model human gastric mucins. First, the identity of the porcine gastric mucins was explored using tandem mass spectrometry and immunohistochemistry. This revealed that Muc5ac was expressed by the surface epithelium and was the prominent mucin in porcine gastric mucus. Muc6 was expressed by gastric submucosal glands, but was not a major component of the secreted mucus barrier. Porcine Muc5ac and Muc6 were shown to be aggregated by EGCG. These data demonstrate that mucins from both saliva and the stomach are substantially altered by EGCG. This may contribute to the astringency and low bioavailability of EGCG. In contrast, the green tea polyphenol epicatechin (EC) did not cause aggregation of salivary mucins or porcine gastric mucins, suggesting that the galloyl ring of EGCG (which is absent in EC) is important for its aggregation of mucins, and that EC has different mechanisms of astringency.The structure of the mucins in the alimentary canal was studied using Raman spectroscopy, Raman optical activity (ROA) and Tip-enhanced Raman spectroscopy (TERS). The secondary structure of the oligosaccharide-rich regions of mucins was shown to be largely disordered, with some contribution of poly-proline II helix. The N- and C-terminal regions of MUC5B were largely β-sheet in structure, with some disordered structure also present in the C-terminal region. Raman spectroscopy could reliably distinguish between MUC5B glycoforms, demonstrating the… Advisors/Committee Members: BLANCH, EWAN EW, Thornton, David, Blanch, Ewan.

Subjects/Keywords: Mucin; Stomach; Mucus; Saliva; MUC5B; MUC7; Muc5ac; Muc6; Green tea polyphenols; Epigallocatechin-3-gallate; EGCG; Raman spectroscopy; Raman optical activity; Tip-enhanced Raman spectroscopy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Davies, H. (2014). Mucins in the alimentary canal: their structure and interactions with polyphenols. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:239764

Chicago Manual of Style (16th Edition):

Davies, Heather. “Mucins in the alimentary canal: their structure and interactions with polyphenols.” 2014. Doctoral Dissertation, University of Manchester. Accessed September 21, 2020. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:239764.

MLA Handbook (7th Edition):

Davies, Heather. “Mucins in the alimentary canal: their structure and interactions with polyphenols.” 2014. Web. 21 Sep 2020.

Vancouver:

Davies H. Mucins in the alimentary canal: their structure and interactions with polyphenols. [Internet] [Doctoral dissertation]. University of Manchester; 2014. [cited 2020 Sep 21]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:239764.

Council of Science Editors:

Davies H. Mucins in the alimentary canal: their structure and interactions with polyphenols. [Doctoral Dissertation]. University of Manchester; 2014. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:239764

3. Βγενοπούλου, Στεφανί. Συμπεριφορά των γλυκοπρωτεϊνών MUC1 και MUC6 στον καρκίνο του μαστού: ανοσοβιολογική μελέτη.

Degree: 2007, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)

We investigated endotumoral and peritumoral lymphocytic subsets [natural killer cells (NK), B-cells and cytotoxic/suppressor (CD8+) T-cells], and expression of MUC1 and MUC6 glycoprotein with regard to various clinicopathological parameters in invasive breast cancer tissues. The study population consisted of 64 female patients with invasive ductal breast cancer of not-otherwise-specified type. Thirty-five women with benign breast lesions served as controls. High-grade carcinomas exhibited higher numbers of endotumoral NK cells and B-cell aggregates than the rest of the tumors examined (P=0,0003 and P=0,027, respectively). Cases with more than three positive lymph nodes and with tumors over 2 cm in diameter exhibited higher numbers of endotumoral NK cells (P=0,047 and P=0,023, respectively). Increased numbers of peritumoral CD8+ T-cells were detected in cases with lymph node metastases (P=0,045). MUC1 was expressed with weaker staining intensity in the control group than in the group with breast cancer (P=0,011). Grade III carcinomas exhibited significantly stronger expression of MUC6 glycoprotein (P=0,001) than the control group. In conclusion, tumors with markers of poor prognosis exhibited increased numbers of lymphocytic infiltrates, and of NK cells in particular, and stronger MUC1 and MUC6 glycoprotein immunoreactivity than did the other tumors.714

Μελετήθηκαν οι λεμφοκυτταρικοί υποπληθυσμοί με ενδο- και περινεοπλασματική κατανομή [φυσικά κύτταρα φονείς (ΝΚ), Β-λεμφοκύτταρα και κυτταροτοξικά κατασταλτικά (CD8+) Τ-λεμφοκύτταρα), καθώς και η έκφραση των γλυκοπρωτεϊνών MUC1 και MUC6 σε σχέση με διάφορες κλινικοπαθολογοανατομικές παραμέτρους σε διηθητικά καρκινώματα του μαστού. Ο πληθυσμός που μελετήθηκε απαρτιζόταν από 64 γυναίκες ασθενείς με διηθητικό πορογενές καρκίνωμα του μαστού μη-περαιτέρω ταξινομούμενου τύπου (non-otherwise-specified, NOS). Σαν ομάδα ελέγχου χρησιμοποιήθηκαν 35 γυναίκες με καλοήθεις αλλοιώσεις του μαστού. Τα υψηλού βαθμού κακοηθείας καρκινώματα παρουσίαζαν υψηλότερους αριθμούς ενδονεοπλασματικών ΝΚ κυττάρων και αθροίσεις Β-λεμφοκυττάρων σε σχέση με τα υπόλοιπα εξεταζόμενα καρκινώματα (Ρ=0,0003 και Ρ=0,027 αντίστοιχα). Περιπτώσεις με περισσότερους από τρεις θετικούς λεμφαδένες και καρκινώματα μεγαλύτερα των 2 εκ. σε διάμετρο, εμφάνιζαν υψηλότερους αριθμούς ενδονεοπλασματικών ΝΚ κυττάρων (Ρ=0,047 και Ρ=0,023 αντίστοιχα). Αυξημένοι αριθμοί περινεοπλασματικών CD8+ Τ-κυττάρων ανιχνεύτηκαν σε περιπτώσεις ασθενών με λεμφαδενικές μεταστάσεις (Ρ=0,045). Η γλυκοπρωτεΐνη MUC1 εκφραζόταν με ασθενέστερη ένταση στην ομάδα ελέγχου από ότι στην ομάδα των ασθενών με καρκίνο του μαστού (Ρ=0,011). Τα καρκινώματα υψηλού βαθμού κακοήθειας (Grade III) εμφάνισαν σημαντικά εντονότερη έκφραση της γλυκοπρωτεΐνης MUC6 (Ρ=0,001) από ότι η ομάδα ελέγχου. Συμπερασματικά, όγκοι με δείκτες πτωχής πρόγνωσης εμφάνισαν αυξημένους αριθμούς λεμφοκυτταρικών διηθήσεων, ιδιαίτερα των κυττάρων φυσικών φονέων (NK cells), καθώς και εντονότερη ανοσο-έκφραση των γλυκοπρωτεϊνών

Subjects/Keywords: Καρκίνος μαστού; Βλεννοπρωτεϊνες; MUC1 βλεννοπρωτεϊνη; MUC6 βλεννοπρωτεϊνη; Breast cancer; TIL (Tumor Infiltrating Lymphocytes); Mucins

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Βγενοπούλου, . . (2007). Συμπεριφορά των γλυκοπρωτεϊνών MUC1 και MUC6 στον καρκίνο του μαστού: ανοσοβιολογική μελέτη. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/17158

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Βγενοπούλου, Στεφανί. “Συμπεριφορά των γλυκοπρωτεϊνών MUC1 και MUC6 στον καρκίνο του μαστού: ανοσοβιολογική μελέτη.” 2007. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed September 21, 2020. http://hdl.handle.net/10442/hedi/17158.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Βγενοπούλου, Στεφανί. “Συμπεριφορά των γλυκοπρωτεϊνών MUC1 και MUC6 στον καρκίνο του μαστού: ανοσοβιολογική μελέτη.” 2007. Web. 21 Sep 2020.

Vancouver:

Βγενοπούλου . Συμπεριφορά των γλυκοπρωτεϊνών MUC1 και MUC6 στον καρκίνο του μαστού: ανοσοβιολογική μελέτη. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2007. [cited 2020 Sep 21]. Available from: http://hdl.handle.net/10442/hedi/17158.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Βγενοπούλου . Συμπεριφορά των γλυκοπρωτεϊνών MUC1 και MUC6 στον καρκίνο του μαστού: ανοσοβιολογική μελέτη. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2007. Available from: http://hdl.handle.net/10442/hedi/17158

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.