Abstract Gastrointestinal (GI) symptoms of SARS-CoV2/COVID-19 in the form of anorexia, nausea, vomiting, abdominal pain and diarrhea are usually preceeded by respiratory manifestations and are associated with a poor prognosis. Hematochezia is an uncommon clinical presentation of COVID-19 disease and we hypothesize that older patients with significant comorbidites (obesity and cardiovascular) and prolonged hospitalization are suspectible to ischemic injury to the bowel. We reviewed the clinical course, key laboratory data including acute phase reactants, drug/medication history in two elderly male patients admitted for COVID-19 respiratory failure. Both patients had a complicated clinical course and suffered from hematochezia and acute blood loss anemia requiring blood transfusion around day 40 of their hospitalization. Colonoscopic impressions were correlated with the histopathological findings in the colonic biopies and changes compatible with ischemia to nonspecific acute inflammation, edema and increased eosinophils in the lamina propria were noted. Both patients were on anticoagulants, multiple antibiotics and antifungal agents due to respiratory infections at the time of lower GI bleeding. Hematochezia resolved spontaneously with supportive care. Both patients eventually recovered and were discharged. Elderly patients with significant comorbid conditions are uniquely at risk for ischemic injury to the bowel. Hypoxic conditions due to COVID-19 pneumonia and respiratory failure, compounded by preexisting cardiovascular complications, and/or cytokine storm orchestrated by the viral infection leading to alteration in coagulation profile and/or drug/medication injury can be difficult to distinguish in these critically ill patients. Presentation of hematochezia may further increase the mortality and morbidity of COVID-19 patients, and prompt consultation and management by gastroenterology is therefore warranted.
Indoleamine 2,3-dioxygenase (IDO) catalyzes the initial, rate-limiting step of tryptophan (Trp) catabolism along the kynurenine (KYN) pathway, and its induction in cells of the immune system in response to cytokines has been implicated in the regulation of antigen presentation and responses to cell-mediated immune attack. Microarray and quantitative PCR analyses of isolated human islets incubated with interferon (IFN)-gamma for 24 h revealed increased expression of IDO mRNA (>139-fold) and Trp-tRNA synthase (WARS) (>17-fold) along with 975 other transcripts more than threefold, notably the downstream effectors janus kinase (JAK)2, signal transducer and activator of transcription (STAT)1, IFN-gamma regulatory factor-1, and several chemokines (CXCL9/MIG, CXCL10/IP10, CXCL11/1-TAC, CCL2, and CCL5/RANTES) and their receptors. IDO protein expression was upregulated in IFN-gamma-treated islets and accompanied by increased intracellular IDO enzyme activity and the release of KYN into the media. The response to IFN-gamma was countered by interleukin-4 and 1alpha-methyl Trp. Immunohistochemical localization showed IDO to be induced in cells of both endocrine, including pancreatic duodenal homeobox 1-positive beta-cells, and nonendocrine origin. We postulate that in the short term, IDO activation may protect islets from cytotoxic damage, although chronic exposure to various Trp metabolites could equally lead to beta-cell attrition.
ABSTRACT How the human intestinal immune system is distinctly organized to respond to inflammation is still poorly understood. Here, we used single-cell RNA-sequencing to examine lamina propria CD45+ hematopoietic cells from patients with inflammatory bowel disease that have undergone ileal pouch-anal anastomosis, or the colon mucosa of ulcerative colitis patients. We identified a population of IL1B + antimicrobial macrophages and FOXP3 /+ BATF + T cells that are associated and expanded in inflamed tissues, which we further validated in other scRNA-seq datasets from IBD patients. CD8+ T cells were unexpectedly more abundant in the pouch than colon. Cell type specific markers obtained from single-cell RNA-sequencing was used to infer representation from bulk RNA sequencing datasets, which further implicated antimicrobial macrophages expressing IL1B with S100A8/A9 calprotectin as being associated with inflammation, as well as Bacteroides and Escherichia bacterial species. Finally, we find that non-responsiveness to anti-integrin biologic therapies in UC patients is associated with the signature of this antimicrobial macrophage population in a subset of patients. This study identified conserved and distinct features of intestinal inflammation between parts of the small and large intestine undergoing similar inflammation conditions.
Objective . We here describe the development of a freely available online database resource, GeneSpeed Beta Cell, which has been created for the pancreatic islet and pancreatic developmental biology investigator community. Research Design and Methods . We have developed GeneSpeed Beta Cell as a separate component of the GeneSpeed database, providing a genomics‐type data repository of pancreas and islet‐relevant datasets interlinked with the domain‐oriented GeneSpeed database. Results . GeneSpeed Beta Cell allows the query of multiple published and unpublished select genomics datasets in a simultaneous fashion (multiexperiment viewing) and is capable of defining intersection results from precomputed analysis of such datasets (multidimensional querying). Combined with the protein‐domain categorization/assembly toolbox provided by the GeneSpeed database, the user is able to define spatial expression constraints of select gene lists in a relatively rigid fashion within the pancreatic expression space. We provide several demonstration case studies of relevance to islet cell biology and development of the pancreas that provide novel insight into islet biology. Conclusions . The combination of an exhaustive domain‐based compilation of the transcriptome with gene array data of interest to the islet biologist affords novel methods for multidimensional querying between individual datasets in a rapid fashion, presently not available elsewhere.
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