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pancreatic inflamation

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https://www.readbyqxmd.com/read/28864875/deciphering-the-pathogenesis-of-human-type-1-diabetes-t1d-by-interrogating-t-cells-from-the-scene-of-the-crime
#1
REVIEW
Sally C Kent, Stuart I Mannering, Aaron W Michels, Jenny Aurielle B Babon
PURPOSE OF REVIEW: Autoimmune-mediated destruction of insulin-producing β-cells within the pancreas results in type 1 diabetes (T1D), which is not yet preventable or curable. Previously, our understanding of the β-cell specific T cell repertoire was based on studies of autoreactive T cell responses in the peripheral blood of patients at risk for, or with, T1D; more recently, investigations have included immunohistochemical analysis of some T cell specificities in the pancreas from organ donors with T1D...
September 2, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28842400/increased-effector-memory-insulin-specific-cd4-t-cells-correlate-with-insulin-autoantibodies-in-recent-onset-type-1-diabetic-patients
#2
Justin A Spanier, Nathanael L Sahli, Joseph C Wilson, Tijana Martinov, Thamotharampillai Dileepan, Adam L Burrack, Erik B Finger, Bruce R Blazar, Aaron W Michels, Antoinette Moran, Marc K Jenkins, Brian T Fife
Type 1 diabetes (T1D) results from T-cell mediated destruction of insulin producing beta cells. Insulin represents a key self-antigen in disease pathogenesis as recent studies identified proinsulin responding T-cells from inflamed pancreatic islets of recent onset T1D organ donors. These cells respond to an insulin B chain epitope presented by human leukocyte antigen (HLA) DQ8 molecule associated with high T1D risk. It is now critical to understand insulin specific T-cell frequency and phenotype in peripheral blood...
August 25, 2017: Diabetes
https://www.readbyqxmd.com/read/28656348/pap-reg3a-favors-perineural-invasion-in-pancreatic-adenocarcinoma-and-serves-as-a-prognostic-marker
#3
Jérémy Nigri, Meritxell Gironella, Christian Bressy, Elena Vila-Navarro, Julie Roques, Sophie Lac, Caroline Bontemps, Coraline Kozaczyk, Jérôme Cros, Daniel Pietrasz, Raphaël Maréchal, Jean-Luc Van Laethem, Juan Iovanna, Jean-Baptiste Bachet, Emma Folch-Puy, Richard Tomasini
Pancreatic ductal adenocarcinoma (PDA) is a fatal and insidious malignant disease for which clinicians' tools are restricted by the current limits in knowledge of how tumor and stromal cells act during the disease. Among PDA hallmarks, neural remodeling (NR) and perineural invasion (PNI) drastically influence quality of life and patient survival. Indeed, NR and PNI are associated with neuropathic pain and metastasis, respectively, both of which impact clinicians' decisions and therapeutic options. The aim of this study was to determine the impact and clinical relevance of the peritumoral microenvironment, through pancreatitis-associated protein (PAP/REG3A) expression, on PNI in pancreatic cancer...
June 27, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28634110/pharmacological-rescue-of-ductal-cftr-rescue-pancreatic-and-salivary-glands-acinar-cells-and-tissue-function-in-mouse-models-of-autoimmune-diseases
#4
Mei Zeng, Mitchell Szymczak, Malini Ahuja, Changyu Zheng, Hongen Yin, William Swaim, John A Chiorini, Robert J Bridges, Shmuel Muallem
BACKGROUND & AIMS: Sjögren's syndrome and autoimmune pancreatitis are disorders with decreased function of salivary, lacrimal glands, and the exocrine pancreas. Nonobese diabetic/ShiLTJ mice and mice transduced with the cytokine BMP6 develop Sjögren's syndrome and chronic pancreatitis and MRL/Mp mice are models of autoimmune pancreatitis. Cystic fibrosis transmembrane conductance regulator (CFTR) is a ductal Cl(-) channel essential for ductal fluid and HCO3(-) secretion. We used these models to ask the following questions: is CFTR expression altered in these diseases, does correction of CFTR correct gland function, and most notably, does correcting ductal function correct acinar function? METHODS: We treated the mice models with the CFTR corrector C18 and the potentiator VX770...
June 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28599853/post-obstructive-cyst-formation-in-pancreas-and-cystic-acinar-transformation-are-they-same
#5
Xuchen Zhang, Hongfa Zhu, Xiu Yang, Volkan N Adsay, Dhanpat Jain
Pancreatic "acinar cell cystadenoma" (PACA) is a rare benign pancreatic cystic lesion showing acinar cell differentiation. The neoplastic nature of PACA has been questioned and its exact pathogenesis remains unclear. To investigate that acinar cell differentiation is a non-specific metaplastic phenomenon that can occur in pancreatic ductal system, especially when chronically inflamed and dilated, and doesn't necessarily imply an acinar cell neoplasm, we retrospectively analyzed cases diagnosed as PACA and cases with post-obstructive cystic dilatation of pancreatic ducts for acinar cell differentiation using immunohistochemistry for trypsin...
August 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28550204/cutting-edge-origins-recruitment-and-regulation-of-cd11c-cells-in-inflamed-islets-of-autoimmune-diabetes-mice
#6
Joanna E Klementowicz, Ashley E Mahne, Allyson Spence, Vinh Nguyen, Ansuman T Satpathy, Kenneth M Murphy, Qizhi Tang
In NOD mice, CD11c(+) cells increase greatly with islet inflammation and contribute to autoimmune destruction of pancreatic β cells. In this study, we investigated their origin and mechanism of recruitment. CD11c(+) cells in inflamed islets resembled classical dendritic cells based on their transcriptional profile. However, the majority of these cells were not from the Zbtb46-dependent dendritic-cell lineage. Instead, monocyte precursors could give rise to CD11c(+) cells in inflamed islets. Chemokines Ccl5 and Ccl8 were persistently elevated in inflamed islets and the influx of CD11c(+) cells was partially dependent on their receptor Ccr5...
July 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28380359/quantitative-multiplex-immunohistochemistry-reveals-myeloid-inflamed-tumor-immune-complexity-associated-with-poor-prognosis
#7
Takahiro Tsujikawa, Sushil Kumar, Rohan N Borkar, Vahid Azimi, Guillaume Thibault, Young Hwan Chang, Ariel Balter, Rie Kawashima, Gina Choe, David Sauer, Edward El Rassi, Daniel R Clayburgh, Molly F Kulesz-Martin, Eric R Lutz, Lei Zheng, Elizabeth M Jaffee, Patrick Leyshock, Adam A Margolin, Motomi Mori, Joe W Gray, Paul W Flint, Lisa M Coussens
Here, we describe a multiplexed immunohistochemical platform with computational image processing workflows, including image cytometry, enabling simultaneous evaluation of 12 biomarkers in one formalin-fixed paraffin-embedded tissue section. To validate this platform, we used tissue microarrays containing 38 archival head and neck squamous cell carcinomas and revealed differential immune profiles based on lymphoid and myeloid cell densities, correlating with human papilloma virus status and prognosis. Based on these results, we investigated 24 pancreatic ductal adenocarcinomas from patients who received neoadjuvant GVAX vaccination and revealed that response to therapy correlated with degree of mono-myelocytic cell density and percentages of CD8(+) T cells expressing T cell exhaustion markers...
April 4, 2017: Cell Reports
https://www.readbyqxmd.com/read/28373582/chronic-fibro-inflammatory-responses-in-autoimmune-pancreatitis-depend-on-ifn-%C3%AE-and-il-33-produced-by-plasmacytoid-dendritic-cells
#8
Tomohiro Watanabe, Kouhei Yamashita, Yasuyuki Arai, Kosuke Minaga, Ken Kamata, Tomoyuki Nagai, Yoriaki Komeda, Mamoru Takenaka, Satoru Hagiwara, Hiroshi Ida, Toshiharu Sakurai, Naoshi Nishida, Warren Strober, Masatoshi Kudo
In previous studies, we found that human IgG4-related autoimmune pancreatitis (AIP) and murine AIP are driven by activation of plasmacytoid dendritic cells (pDCs) producing IFN-α. In the present studies we examined additional roles of pDC-related mechanisms in AIP pathogenesis, particularly those responsible for induction of fibrosis. We found that in murine AIP (MRL/Mp mice treated with polyinosinic-polycytidylic acid) not only the pancreatic infiltration of immune cells but also the development of fibrosis were markedly reduced by the depletion of pDCs or blockade of type I IFN signaling; moreover, such treatment was accompanied by a marked reduction of pancreatic expression of IL-33...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28363903/ifn-regulatory-factor-3-potentiates-emphysematous-aggravation-by-lipopolysaccharide
#9
Takashi Ishii, Keisuke Hosoki, Yuichi Nikura, Naohide Yamashita, Takahide Nagase, Naomi Yamashita
Acute exacerbation of chronic obstructive pulmonary disease (COPD) is often induced by infection and often has a poor prognosis. Bacterial LPS activates innate immune receptor TLR4 followed by activation of a transcriptional factor IFN regulatory factor-3 (IRF3) as well as NF-κB, resulting in upregulation of various inflammatory mediators. To clarify the role of IRF3 in the pathogenesis of LPS-triggered COPD exacerbation, porcine pancreatic elastase (PPE) followed by LPS was administered intranasally to wild-type (WT) or IRF3(-/-) male mice...
May 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28322389/alteration-of-pancreatic-carcinoma-and-promyeloblastic-cell-adhesion-in-liver-microvasculature-by-co-culture-of-hepatocytes-hepatic-stellate-cells-and-endothelial-cells-in-a-physiologically-relevant-model
#10
Mathieu Danoy, Marie Shinohara, Astia Rizki-Safitri, Dominique Collard, Vincent Senez, Yasuyuki Sakai
In vitro models of the liver microvasculature, especially with respect to cancer cell extravasation, should include not only endothelial and cancer cells but also surrounding cells to mimic the physiological situation. To this end, in the present study, we established a physiologically-relevant hierarchical co-culture model by stacking layers of primary rat hepatocytes (Hep), hepatic stellate cells embedded in collagen gel (LX-2) and endothelial cells (HUVECs) on a specially designed oxygen-permeable polydimethylsiloxane PDMS bottom plate...
April 18, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28236277/dual-drainage-using-a-percutaneous-pancreatic-duct-technique-contributed-to-resolution-of-severe-acute-pancreatitis
#11
Tatsunori Satoh, Masataka Kikuyama, Yoshihiro Yokoi, Shinya Kawaguchi
A 66-year-old man was admitted for severe acute alcoholic pancreatitis with infected pancreatic necrosis (IPN). Abdominal computed tomography revealed an inflamed pancreatic head, a dilated main pancreatic duct (MPD), and a large cavity with heterogeneous fluid containing gas adjacent to the pancreatic head, and extending to the pelvis. The cavity was drained percutaneously near the pancreatic head on admission; another tube was inserted into the pelvic cavity on hospital day 3. The drained fluid contained pus with high amylase concentration...
April 2017: Clinical Journal of Gastroenterology
https://www.readbyqxmd.com/read/28025477/duodenal-loop-obstruction-as-an-unusual-cause-of-acute-pancreatitis-a-case-series
#12
Hyeonmin Lee, Yonghyeok Choi, Hyewon Jeong, Jae Kyu Lim, Taeyoung Jung, Joung Ho Han, Seon Mee Park
Duodenal loop obstruction is an unusual cause of acute pancreatitis. Increased intraluminal pressure hinders pancreatic flow, causing dilatation of the pancreatic duct and inducing acute pancreatitis. We experienced three cases of acute pancreatitis that resulted from duodenal loop obstruction after (1) an esophagectomy with gastric pull-up procedure for esophageal cancer, (2) a gastrectomy with Billroth I reconstruction for gastric cancer, and (3) a gastrojejunostomy for abdominal trauma. An abdominal CT scan revealed a distended duodenal loop, dilated pancreatic duct, and inflamed pancreas with fluid collection...
December 25, 2016: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/27923620/fluorescent-diphenylphosphonate-based-probes-for-detection-of-serine-protease-activity-during-inflammation
#13
Laura E Edgington-Mitchell, Nicholas Barlow, Luigi Aurelio, Aminath Samha, Monika Szabo, Bim Graham, Nigel Bunnett
Activity-based probes are small molecules that covalently bind to the active site of a protease in an activity-dependent manner. We synthesized and characterized two fluorescent activity-based probes that target serine proteases with trypsin-like or elastase-like activity. We assessed the selectivity and potency of these probes against recombinant enzymes and demonstrated that while they are efficacious at labeling active proteases in complex protein mixtures in vitro, they are less valuable for in vivo studies...
January 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27920643/elevated-lipase-during-initial-presentation-of-ulcerative-colitis-in-a-pediatric-patient-do-we-check-for-it
#14
Piyali Ray, Melissa R Van Arsdall
There are very few reports of elevated lipase in pediatric inflammatory bowel disease (IBD). Symptoms of pancreatitis may be masked by abdominal pain in pediatric IBD. During the initial presentation of IBD in our patient, lipase was elevated to more than 3 times the upper limit of normal. Normalization of values coincided with remission of IBD. This may be due to extraintestinal involvement of the pancreas as part of the inflammatory process or due to leakage of pancreatic enzymes from an inflamed gut or mediated by inflammatory cytokines...
September 2016: Case Reports in Gastroenterology
https://www.readbyqxmd.com/read/27920090/islet-derived-cd4-t-cells-targeting-proinsulin-in-human-autoimmune-diabetes
#15
Aaron W Michels, Laurie G Landry, Kristen A McDaniel, Liping Yu, Martha Campbell-Thompson, William W Kwok, Kenneth L Jones, Peter A Gottlieb, John W Kappler, Qizhi Tang, Bart O Roep, Mark A Atkinson, Clayton E Mathews, Maki Nakayama
Type 1 diabetes results from chronic autoimmune destruction of insulin-producing β-cells within pancreatic islets. Although insulin is a critical self-antigen in animal models of autoimmune diabetes, due to extremely limited access to pancreas samples, little is known about human antigenic targets for islet-infiltrating T cells. Here we show that proinsulin peptides are targeted by islet-infiltrating T cells from patients with type 1 diabetes. We identified hundreds of T cells from inflamed pancreatic islets of three young organ donors with type 1 diabetes with a short disease duration with high-risk HLA genes using a direct T-cell receptor (TCR) sequencing approach without long-term cell culture...
March 2017: Diabetes
https://www.readbyqxmd.com/read/27843953/considerations-for-defining-cytokine-dose-duration-and-milieu-that-are-appropriate-for-modeling-chronic-low-grade-inflammation-in-type-2-diabetes
#16
REVIEW
Craig S Nunemaker
Proinflammatory cytokines have been implicated in the pathophysiology of both type 1 diabetes (T1D) and type 2 diabetes (T2D). T1D is an autoimmune disease involving the adaptive immune system responding to pancreatic beta-cells as antigen-presenting cells. This attracts immune cells that surround pancreatic islets (insulitis) and secrete cytokines, such as IL-1beta, IFN-gamma, and TNF-alpha, in close proximity to pancreatic beta-cells. In contrast, there is little evidence for such a focused autoimmune response in T2D...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27366048/prospective-small-bowel-mucosal-assessment-immediately-after-chemoradiotherapy-of-unresectable-locally-advanced-pancreatic-cancer-using-capsule-endoscopy-a-case-series
#17
Takeshi Yamashina, Ryoji Takada, Noriya Uedo, Tomofumi Akasaka, Noboru Hanaoka, Yoji Takeuchi, Koji Higashino, Tatsuya Ioka, Ryu Ishihara, Teruki Teshima, Kinji Nishiyama, Hiroyasu Iishi
In this case series, three consecutive patients with unresectable locally advanced pancreatic cancer (ULAPC) underwent capsule endoscopy (CE) before and after chemoradiotherapy (CRT) to evaluate duodenal and jejunal mucosa, and to examine the relationship between CE findings and dose distribution. CE after CRT showed duodenitis and proximal jejunitis in all three patients. The most inflamed region was the third part of the duodenum, and in dose distribution, this was the closest region to the center of irradiation...
July 2016: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
https://www.readbyqxmd.com/read/27343548/combination-of-radiotherapy-and-vaccination-overcomes-checkpoint-blockade-resistance
#18
Wenxin Zheng, Kinga B Skowron, Jukes P Namm, Byron Burnette, Christian Fernandez, Ainhoa Arina, Hua Liang, Michael T Spiotto, Mitchell C Posner, Yang-Xin Fu, Ralph R Weichselbaum
The majority of cancer patients respond poorly to either vaccine or checkpoint blockade, and even to the combination of both. They are often resistant to high doses of radiation therapy as well. We examined prognostic markers of immune cell infiltration in pancreatic cancer. Patients with low CD8+ T cell infiltration and high PD-L1 expression (CD8+ TloPD-L1hi) experienced poor outcomes. We developed a mouse tumor fragment model with a trackable model antigen (SIYRYYGL or SIY) to mimic CD8+ TloPD-L1hi cancers...
July 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27183218/platelet-derived-cxcl4-regulates-neutrophil-infiltration-and-tissue-damage-in-severe-acute%C3%A2-pancreatitis
#19
Erik Wetterholm, Johan Linders, Mohammed Merza, Sara Regner, Henrik Thorlacius
Platelets are known to play an important role in acute pancreatitis (AP) via promotion of neutrophil accumulation, although mechanisms behind platelet-dependent accumulation of neutrophils in the pancreas remain elusive. Platelets contain a wide spectrum of different pro-inflammatory compounds, such as chemokines. CXCL4 (platelet factor 4) is one of the most abundant chemokine in platelets, and we hypothesized that CXCL4 might be involved in platelet-dependent accumulation of neutrophils in the inflamed pancreas...
October 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27044747/ubiquitin-d-regulates-ire1%C3%AE-c-jun-n-terminal-kinase-jnk-protein-dependent-apoptosis-in-pancreatic-beta-cells
#20
Flora Brozzi, Sarah Gerlo, Fabio Arturo Grieco, Matilda Juusola, Alexander Balhuizen, Sam Lievens, Conny Gysemans, Marco Bugliani, Chantal Mathieu, Piero Marchetti, Jan Tavernier, Décio L Eizirik
Pro-inflammatory cytokines contribute to pancreatic beta cell apoptosis in type 1 diabetes at least in part by inducing endoplasmic reticulum (ER) stress and the consequent unfolded protein response (UPR). It remains to be determined what causes the transition from "physiological" to "apoptotic" UPR, but accumulating evidence indicates that signaling by the ER transmembrane protein IRE1α is critical for this transition. IRE1α activation is regulated by both intra-ER and cytosolic cues. We evaluated the role for the presently discovered cytokine-induced and IRE1α-interacting protein ubiquitin D (UBD) on the regulation of IRE1α and its downstream targets...
June 3, 2016: Journal of Biological Chemistry
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