3,467 research outputs found
GPR15L-dependent lymphocyte trafficking in inflammatory bowel disease
No full textHintergrund und Ziele:
Die Prävalenz chronisch entzündlicher Darmerkrankungen (CED) hat seit dem letzten Jahrhundert in den Industrieländern zugenommen. Jedoch konnte die genaue Pathogenese dieser Erkrankungen bisher noch nicht abschließend geklärt werden und die therapeutischen Möglichkeiten sind nach wie vor begrenzt. Ein wichtiger Mechanismus im Krankheitsprozess der CED ist die Auswanderung von Immunzellen aus der Blutzirkulation in das Darmgewebe. Dieser Mechanismus wird „Darmhoming“ genannt. Er besteht aus mehreren Schritten, von denen einer die Chemokin-induzierte Zellaktivierung ist, welche die Voraussetzung für eine feste Bindung an der Endotheloberfläche schafft. Diese Aktivierung wird über G-Protein-gekoppelte Rezeptoren vermittelt und führt hierüber zur einer Konformationsänderung der Oberflächenintegrine, wodurch eine feste Bindung an die Zelladhäsionsmoleküle der Endothelzellen ermöglicht wird. Bisherige Daten legen nahe, dass der G-Protein-gekoppelte Rezeptor 15 (GPR15) insbesondere die Einwanderung von T-Zellen in das Colon beeinflusst. GPR15 wurde daher bereits als therapeutische Zielstruktur für die Colitis im Rahmen von CED postuliert. Limitierend war bislang, dass der endogene Ligand von GPR15 (GPR15L) bis 2017 nicht bekannt war. Die Bedeutung von GPR15L im Kontext von CED ist daher noch unklar. Das Ziel dieser Dissertation war es daher, die Rolle von GPR15L genauer zu untersuchen. Die Hypothese war, dass GPR15L durch Steuerung des T-Lymphozytenhomings in den Dickdarm
zur Pathogenese intestinaler Entzündungsreaktionen beiträgt.
Methoden:
Um dieser Hypothese nachzugehen, wurden T-Lymphozyten humaner Spender in vitro mit funktionellen dynamischen Adhäsionsassays untersucht. Des Weiteren wurde die Ko-Expression von GPR15 mit Darmhoming-relevanten Integrinen in durchflusszytometrischen Untersuchungen in T-Zell-Subsets gesunder Spender und von Patienten mit CED beurteilt. Es wurden experimentelle DSS-Colitismodelle (Natrium-Dextransulfat, engl.: „dextran sulfate sodium“) der Maus, unter Verwendung einer GPR15L-überexprimierenden Mauslinie, untersucht. Der Schweregrad der Colitis wurde klinisch, endoskopisch, histologisch und durch in vivo-Bildgebungsverfahren beurteilt.
Ergebnisse und Beobachtungen:
Die Untersuchungen zeigen in vitro eine vermehrte Adhäsion von T-Zellen an die intestinalen Zelladhäsionsmoleküle MAdCAM-1 (engl.: „mucosal vascular addressin cell adhesion molecule 1“) und VCAM-1 (engl.: „vascular cell adhesion molecule 1“) nach Inkubation mit GPR15L. Weiterhin bestätigen Daten von humanen CD4+ T-Zellen eine hohe Ko-Expression von GPR15 und den Darmhoming-spezifischen Integrinen α4β7 und α4β1. Im DSS-Colitismodell zeigt sich bei GPR15L-überexprimierenden Mäusen eine geringere entzündliche Aktivität im Vergleich zu Wildtyp-Geschwistertieren. Eine zusätzliche Behandlung mit anti-α4β7-Antikörpern egalisierte diesen Effekt und spricht daher für einen Homing-abhängigen protektiven Einfluss von GPR15L in einer experimentellen Colitis.
Schlussfolgerungen:
Zusammenfassend zeigt die vorliegende Arbeit, dass GPR15L Einfluss auf das Darmhoming von T- Zellen in den Integrinen vorgeschalteten Signalkaskaden ausübt und daher eine vielversprechende Zielstruktur für eine zukünftige organselektive Therapie bei
CED sein könnte.Objectives:
The prevalence of inflammatory bowel diseases (IBDs) in industrialized countries has been increasing since the last century. However, the exact pathogenesis of these diseases is still unknown, and the therapeutic options are limited. A crucial process in the pathogenesis of IBDs is the extravasation of immune cells from the blood circulation into the intestinal tissues. This process is called gut homing. It consists of several steps, one of which is the chemokine-induced cell activation, which is necessary for a firm arrest at the endothelium. This activation is induced by G protein-coupled receptors and leads to conformational changes in surface integrins,
thereby allowing firm binding to cell adhesion molecules on endothelial cells. Recent studies indicated that the G protein-coupled receptor 15 (GPR15) selectively regulates gut homing of T cells to the large intestine. Therefore, GPR15 has been strongly suggested as a potential therapeutic target for colitis in IBDs. Further research in the field has been facing the problem that the ligand for GPR15 (GPR15L) had been unknown until 2017. The impact of GPR15L on IBDs is unclear so far. Thus, the role of GPR15L was further investigated in this doctoral thesis. The hypothesis was, that by controlling the homing process of T lymphocytes to the large
intestine, GPR15L contributes to the pathogenesis of intestinal inflammation.
Design and methods:
To address this question, T lymphocytes derived from human blood samples were studied in vitro with functional dynamic adhesion assays. Further, co-expression of GPR15 and gut-homing integrins was assessed with flow cytometry in T cell subsets from healthy donors and patients with IBDs. Experimental DSS (dextran sulfate sodium) mouse models for IBDs were used taking advantage of a GPR15L-overexpressing mouse strain. Severity of colitis was characterized by clinical disease activity, endoscopy, histology, and in vivo imaging.
Observations and results:
The findings show in vitro an increased adhesion of T cells to the intestinal cell adhesion molecules MAdCAM-1 (mucosal vascular addressin cell adhesion molecule 1) and VCAM-1 (vascular cell adhesion molecule 1) after incubation with GPR15L. Additionally, data of human CD4+ T cells confirm a high co-expression of GPR15 with gutspecific homing integrins α4β7 and α4β1. Moreover, GPR15L-overexpressing mice develop less inflammation in the DSS colitis model compared to wildtype littermates. Additional treatment with anti-α4β7 antibodies abrogated this effect, suggesting a homing-dependent protective influence
of GPR15L in experimental colitis.
Conclusions:
In summary, this doctoral thesis shows that GPR15L controls T lymphocyte gut homing upstream of integrins and might thus be a promising target for future organ-selective treatment of IBDs
sj-docx-2-tag-10.1177_17562848231218555 – Supplemental material for Long-term outcomes of cyclosporin induction and ustekinumab maintenance combination therapy in patients with steroid-refractory acute severe ulcerative colitis
No full textSupplemental material, sj-docx-2-tag-10.1177_17562848231218555 for Long-term outcomes of cyclosporin induction and ustekinumab maintenance combination therapy in patients with steroid-refractory acute severe ulcerative colitis by Francesco Vitali, Timo Rath, Entcho Klenske, Anna-Lena Vögele, Ingo Ganzleben, Sebastian Zundler, Deike Strobel, Carol Geppert, Arndt Hartmann, Markus F. Neurath and Raja Atreya in Therapeutic Advances in Gastroenterology</p
Episode 35: Alexis Castellanos, Author of “Isla to Island”, and Her Panel Presentation during the Operación Pedro Pan Two-Day Event
No full textIn Part 1 of “Operación Pedro Pan: The Voices and Stories of Cuba’s Child Exodus—A Knights HistoryCast Mini-Series,” the Department of History’s Sebastian Garcia talked with Alexis Castellanos, an author, illustrator, graphic novelist, and a panelist at the esteemed, conspicuous, and powerful “Operación Pedro Pan: Honoring the Cultural, Historical Legacy of Cuba’s Child Exodus” Two-Day Program that Florida Humanities, UCF’s Department of English and Department of Modern Languages and Literatures sponsored (see https://cah.ucf.edu/pedro-pan/ for more details on sponsors and the program in general).
Sebastian structured this specific episode on Alexis Castellanos’ Isla to Island, a wordless graphic novel grounded by her personal family history and the history of Operación Pedro Pan (Operation Peter Pan). By analyzing such a historic event through the medium of fiction, Sebastian argued that this is one of the most unique Knights HistoryCast episodes of all time. Naturally, their conversation expanded to what she talked about during her panel presentation in Panel One, Day 1 of the event that featured “internationally renowned scholars that discussed the political, historical, and cultural legacy of Operación Pedro Pan (1960-1962).” (https://cah.ucf.edu/pedro-pan/)
To purchase Isla to Island (strongly recommend), check out: https://islatoisland.com/.
To find out more about Alexis and her professional work, check out her website at https://alexiscastellanos.com/https://stars.library.ucf.edu/knightshistorycast/1034/thumbnail.jp
sj-tif-1-tag-10.1177_17562848221098899 – Supplemental material for Vedolizumab blocks α4β7 integrin-mediated T cell adhesion to MAdCAM-1 in microscopic colitis
No full textSupplemental material, sj-tif-1-tag-10.1177_17562848221098899 for Vedolizumab blocks α4β7 integrin-mediated T cell adhesion to MAdCAM-1 in microscopic colitis by Laura Besendorf, Tanja M. Müller, Carol-Immanuel Geppert, Ines Schneider, Laura Mühl, Imke Atreya, Francesco Vitali, Raja Atreya, Markus F. Neurath and Sebastian Zundler in Therapeutic Advances in Gastroenterology</p
sj-docx-1-tag-10.1177_17562848231218555 – Supplemental material for Long-term outcomes of cyclosporin induction and ustekinumab maintenance combination therapy in patients with steroid-refractory acute severe ulcerative colitis
No full textSupplemental material, sj-docx-1-tag-10.1177_17562848231218555 for Long-term outcomes of cyclosporin induction and ustekinumab maintenance combination therapy in patients with steroid-refractory acute severe ulcerative colitis by Francesco Vitali, Timo Rath, Entcho Klenske, Anna-Lena Vögele, Ingo Ganzleben, Sebastian Zundler, Deike Strobel, Carol Geppert, Arndt Hartmann, Markus F. Neurath and Raja Atreya in Therapeutic Advances in Gastroenterology</p
"Cronica der Turckey" Sebastian Franck's Translation of the "Tractatus de Moribus, Condicionibus et Nequitia Turcorum" by Georgius de Hungaria
Full text linkThe Tractatus de moribus, condicionibus et nequitia Turcorum is one of the most important first-hand accounts of life in fifteenth-century Turkey known to modern scholarship. It is the work of a Christian former slave of the Turks, writing after his return to the West. Although the author does not name himself, he can be identified as a
Dominican priest, Georgius de Hungaria, who died in Rome in 1502. His Tractatus is conceived as a work of anti-Islamic polemic, yet it contains a surprisingly unbiased appraisal of Turkish customs.
First printed c.1480 when European apprehension in the face of Ottoman expansion was at its height, the Tractatus was reprinted in numerous editions, and was widely used as a
source by other authors. Luther edited the text in 1530, using the positive account of Turkish customs and religious observance as a weapon in his polemic against the Roman
Catholic Church: if heathens could perform such exemplary works, who could fail to doubt the efficacy of works as a means of salvation?
Sebastian Franck in his German translation of the Tractatus went further: replacing Georgius' commentary with his own, he used the text to attack institutional religion as a
whole and to promote his concept of a non-dogmatic, spiritual Church of individuals united with each other only through their union with God -a Church which was not closed to Moslems or members of any other creed. This translation or adaptation, the Cronica der Türckey, marks Franck's decisive break with the Lutheran cause and the beginning of his lonely path as a 'spiritual individualist'. Franck reworked his translation of the Tractatus for his major geographical work, the Weltbuch of 1534.
This thesis concerns itself primarily with Franck's Cronica, providing the first modern critical edition of this text, in a near-diplomatic transcription with an extensive glossary. The thesis also includes transcriptions of the Tractatus; of Türckei, an anonymous translation of the Tractatus, and of relevant additional material from Franck's Weltbuch. None of these texts has been published in full in a modern edition.
In the Introduction Franck's Cronica is compared in detail with the Tractatus, highlighting the changes that occur in translation; the character and the significance of these changes are then discussed. It is established that Franck, whilst being unwilling to reverse any of Georgius' value judgements on Islam and Turkish culture, is highly selective in his choice of material for translation, and frequently gives the text new nuances and adds his own
comment. The question of the Tractatus' influence on Franck's further development as a writer and thinker is also raised.
The investigation then turns to Franck's use of the Tractatus material in his Weltbuch. His eclecticism becomes apparent in this text, in which Georgius' account is juxtaposed - but not synthesised - with material from other sources, often of lesser veracity and greater anti-Islamic bias. Franck's distortion of the Tractatus material to suit his own line of argument is clearly discernible: from the unique phenomenon presented in the Tractatus the Turks
become one more example of the general human tendency to externalise and dogmatise faith.
In addition, the transmission of Cronica and Türckei is examined, and the relationship between these two translations is clarified: Franck certainly used Türckei in writing his Cronica, but is unlikely to be the author of the anonymous work
sj-docx-1-tag-10.1177_17562848211054707 – Supplemental material for α4β7 integrin-dependent adhesion of T cells to MAdCAM-1 is blocked by vedolizumab in patients with chronic refractory pouchitis
No full textSupplemental material, sj-docx-1-tag-10.1177_17562848211054707 for α4β7 integrin-dependent adhesion of T cells to MAdCAM-1 is blocked by vedolizumab in patients with chronic refractory pouchitis by Michaela Melde, Tanja M. Müller, Ines Schneider, Carol-Immanuel Geppert, Laura Mühl, Laura Besendorf, Clarissa Allner, Emily Becker, Imke Atreya, Francesco Vitali, Raja Atreya, Markus F. Neurath and Sebastian Zundler in Therapeutic Advances in Gastroenterology</p
Diagnostic Endoscopic Ultrasound in Pancreatology: Focus on Normal Variants and Pancreatic Masses
Full text linkBackground: Endoscopic ultrasound (EUS) is a main tool in gastroenterology for both diagnosis and exclusion of pancreatic pathology. It allows minimally invasive assessment of various diseases or anatomic variations affecting the pancreas also with the help of new Doppler technologies, elastography, contrast-enhanced imaging including post hoc image processing with quantification analyses, three-dimensional reconstruction, and artificial intelligence. EUS also allows interventional direct access to the pancreatic parenchyma and the retroperitoneal space, to the pancreatic duct, pancreatic masses, cysts, and vascular structures. Summary: This review aimed to summarize new developments of EUS in the field of pancreatology. We highlight the role of EUS in evaluating pancreatic pathology by describing normal anatomic variants like pancreas divisum, pancreatic lipomatosis, pancreatic fibrosis in the elderly and characterizing pancreatic masses, both in the context of chronic pancreatitis and within healthy pancreatic parenchyma. EUS is considered the optimal imaging modality for pancreatic masses of uncertain dignity and allows both cytological diagnosis and histology, which is essential not only for neoplastic conditions but also for tailoring therapy for benign inflammatory conditions. Key Messages: EUS plays an indispensable role in pancreatology and the development of new diagnostic and interventional approaches to the retroperitoneal space and the pancreas exponentially increased over the last years. The development of computer-aided diagnosis and artificial intelligence algorithms hold the potential to overcome the obstacles associated with interobserver variability and will most likely support decision-making in the management of pancreatic disease
2. A Human Being to Be Remembered | The 2024 UCF VLP Podcast Series
No full textIn Episode Two, Andrew Carroll’s herculean efforts to seek and collect over 210,000 war letters—that span since the American Revolution—demonstrate how others are as seriously committed to preserving the legacies of the men and women who served and fought for their country. Andrew shares several letters from his impressive collection, allowing us to be as close as possible to the Veterans—engaging with their own words, thoughts, and emotions. Indeed, themes central to UCF VLP are often exemplified in the 210,000 war letters Andrew has preserved for over twenty-five years.
Andrew Carroll is an award-winning historian and author and is the founder and director of the Center for American War Letters at Chapman University. Andrew was the second keynote speaker invited to share his extraordinary work during the 2024 UCF VLP Institute.
This episode was directed, produced, written, edited, and hosted by Sebastian Garcia and featured Andrew Carroll.
Executive Producers: Sebastian Garcia and Dr. Amelia Lyons.
Music: “Honor and Glory” and “Real Heroes” by SergePavkinMusic (Pixabay)
Podcast Cover Artwork: Sebastian Garcia
The 2024 UCF VLP Podcast Series is brought to you by the UCF History Department Podcast Network and UCF’s Veterans Legacy Program—a partnership with the U.S. Department of Veterans Affairs’ National Cemetery Administration.https://stars.library.ucf.edu/knightshistorycast/1051/thumbnail.jp
Wang Tao’s Diary: excerpts Translated by Sebastian Eicher
No full textIn a little regarded episode from Wang Tao’s diaries, the author tells us about a two-week long journey from Shanghai to Hangzhou and to the West Lake. Wang Tao undertook this journey together with the missionary Griffith John, who at that time was trying to find ways to preach the gospel outside the treaty port of Shanghai. We know the rough outline of this journey from Griffith John’s writings, as it was the second half of a longer journey along the Grand Canal. But Wang Tao’s presence and his notes on it have so far been neglected. This is a loss, as the diary Wang Tao kept offers not only a personal and lively account of the journey, it also gives us some insight in the Chinese perception of the missionaries’ activities and a description of the Hangzhou era before the Taiping would ravage it only a bit more than a year later
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