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pancreatic inflamation

C Danny Darlington, G Fatima Shirly Anitha
Meckel's diverticulum is a remnant of the proximal part of the vitellointestinal duct and is the most common congenital anomaly of the gastrointestinal tract. It may either remain asymptomatic or present with myriad of clinical presentations. Gastrointestinal bleeding is the most common presentation in children whereas it is intestinal obstruction in the case of adults. We report a 9-year-old boy who presented with acute onset of periumbilical pain and nonbilious vomiting. His clinical and laboratory parameters were unremarkable, except for serum amylase levels...
November 2017: Indian Journal of Critical Care Medicine
Andres Rubiano, Daniel Delitto, Song Han, Michael Gerber, Carly Galitz, Jose Trevino, Ryan M Thomas, Steven J Hughes, Chelsey S Simmons
Pancreatic ductal adenocarcinoma (PDAC) is almost universally fatal, in large part due to a protective fibrotic barrier generated by tumor-associated stromal (TAS) cells. This barrier is thought to promote cancer cell survival and confounds attempts to develop effective therapies. We present a 3D in vitro system that replicates the mechanical properties of the PDAC microenvironment, representing an invaluable tool for understanding the biology of the disease. Mesoscale indentation quantified viscoelastic metrics of resected malignant tumors, inflamed chronic pancreatitis regions, and histologically normal tissue...
February 2018: Acta Biomaterialia
Nadine Nagy, Adi de la Zerda, Gernot Kaber, Pamela Y Johnson, Kenneth H Hu, Michael J Kratochvil, Koshika Yadava, Wenting Zhao, Yi Cui, Guadalupe Navarro, Justin P Annes, Thomas N Wight, Sarah C Heilshorn, Paul L Bollyky, Manish J Butte
We have identified a novel role for hyaluronan (HA), an extracellular matrix polymer, in governing the mechanical properties of inflamed tissues. We recently reported that insulitis in type 1 diabetes of mice and humans is preceded by intraislet accumulation of HA, a highly hygroscopic polymer. Using the double transgenic DO11.10 × RIPmOVA (DORmO) mouse model of type 1 diabetes, we asked whether autoimmune insulitis was associated with changes in the stiffness of islets. To measure islet stiffness, we used atomic force microscopy (AFM) and developed a novel "bed of nails"-like approach that uses quartz glass nanopillars to anchor islets, solving a long-standing problem of keeping tissue-scale objects immobilized while performing AFM...
January 12, 2018: Journal of Biological Chemistry
Peter Szatmary, Tingting Liu, Simon T Abrams, Svetlana Voronina, Li Wen, Michael Chvanov, Wei Huang, Guozheng Wang, David N Criddle, Alexey V Tepikin, Cheng-Hock Toh, Robert Sutton
BACKGROUND: Clinical and experimental acute pancreatitis feature histone release within the pancreas from innate immune cells and acinar cell necrosis. In this study, we aimed to detail the source of circulating histones and assess their role in the pathogenesis of acute pancreatitis. METHODS: Circulating nucleosomes were measured in patient plasma, taken within 24 and 48 h of onset of acute pancreatitis and correlated with clinical outcomes. Using caerulein hyperstimulation, circulating histones were measured in portal, systemic venous and systemic arterial circulation in mice, and the effects of systemic administration of histones in this model were assessed...
November 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
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
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 β-cells. Insulin represents a key self-antigen in disease pathogenesis, as recent studies identified proinsulin-responding T cells from inflamed pancreatic islets of organ donors with recent-onset T1D. These cells respond to an insulin B-chain (InsB) epitope presented by the HLA-DQ8 molecule associated with high T1D risk. Understanding insulin-specific T-cell frequency and phenotype in peripheral blood is now critical. We constructed fluorescent InsB10-23 :DQ8 tetramers, stained peripheral blood lymphocytes directly ex vivo, and show DQ8+ patients with T1D have increased tetramer+ CD4+ T cells compared with HLA-matched control subjects without diabetes...
December 2017: Diabetes
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...
November 2017: Cellular and Molecular Life Sciences: CMLS
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...
October 2017: Gastroenterology
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
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
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
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
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
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
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
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
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
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
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
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
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