scholarly journals Regionally Distinct Immune and Metabolic Transcriptional Responses in the Bovine Small Intestine and Draining Lymph Nodes During a Subclinical Mycobacterium avium subsp. paratuberculosis Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Eveline M. Ibeagha-Awemu ◽  
Nathalie Bissonnette ◽  
Duy N. Do ◽  
Pier-Luc Dudemaine ◽  
Mengqi Wang ◽  
...  
Keyword(s):  
Small Intestine ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Mycobacterium Avium ◽  
Functional Enrichment ◽  
Host Responses ◽  
Immune Disease ◽  
Term Survival ◽  
Go Terms ◽  
Disease Pathways

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative infectious agent of Johne’s disease (JD), an incurable granulomatous enteritis affecting domestic livestock and other ruminants around the world. Chronic MAP infections usually begin in calves with MAP uptake by Peyer’s patches (PP) located in the jejunum (JE) and ileum (IL). Determining host responses at these intestinal sites can provide a more complete understanding of how MAP manipulates the local microenvironment to support its long-term survival. We selected naturally infected (MAPinf, n=4) and naive (MAPneg, n=3) cows and transcriptionally profiled the JE and IL regions of the small intestine and draining mesenteric lymph nodes (LN). Differentially expressed (DE) genes associated with MAP infection were identified in the IL (585), JE (218), jejunum lymph node (JELN) (205), and ileum lymph node (ILLN) (117). Three DE genes (CD14, LOC616364 and ENSBTAG00000027033) were common to all MAPinf versus MAPneg tissues. Functional enrichment analysis revealed immune/disease related biological processes gene ontology (GO) terms and pathways predominated in IL tissue, indicative of an activated immune response state. Enriched GO terms and pathways in JE revealed a distinct set of host responses from those detected in IL. Regional differences were also identified between the mesenteric LNs draining each intestinal site. More down-regulated genes (52%) and fewer immune/disease pathways (n=5) were found in the ILLN compared to a higher number of up-regulated DE genes (56%) and enriched immune/disease pathways (n=13) in the JELN. Immunohistochemical staining validated myeloid cell transcriptional changes with increased CD172-positive myeloid cells in IL and JE tissues and draining LNs of MAPinf versus MAPneg cows. Several genes, GO terms, and pathways related to metabolism were significantly DE in IL and JE, but to a lesser extent (comparatively fewer enriched metabolic GO terms and pathways) in JELN suggesting distinct regional metabolic changes in IL compared to JE and JELN in response to MAP infection. These unique tissue- and regional-specific differences provides novel insight into the dichotomy in host responses to MAP infection that occur throughout the small intestine and mesenteric LN of chronically MAP infected cows.

scholarly journals Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Nancy G. Casanova ◽  
Manuel L. Gonzalez-Garay ◽  
Belinda Sun ◽  
Christian Bime ◽  
Xiaoguang Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Mediastinal Lymph Node ◽  
Immunological Response ◽  
Functional Enrichment ◽  
Genomic Biomarkers ◽  
Genomic Markers ◽  
Embedded Blocks ◽  
Granulomatous Diseases

Abstract Rationale Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures. Objective To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis). Methods Transcriptomic profiles of immune-related gene from micro-dissected sarcoidosis granulomas within lung and mediastinal lymph node tissues and compared to infectious granulomas from paraffin-embedded blocks. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways. Results Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers (STAB1, HBEGF, and NOTCH4), excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, NPR1 and CXCL2. Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level. Conclusion These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.

scholarly journals Host Responses to Persistent Mycobacterium avium SubspeciesparatuberculosisInfection in Surgically Isolated Bovine Ileal Segments

2012 ◽  
Vol 20 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Chandrashekhar Charavaryamath ◽  
Patricia Gonzalez-Cano ◽  
Patrick Fries ◽  
Susantha Gomis ◽  
Kimberley Doig ◽  
...  
Keyword(s):  
Lymph Node ◽  
T Cell ◽  
Lamina Propria ◽  
Mycobacterium Avium ◽  
Mesenteric Lymph Node ◽  
Cell Receptor ◽  
Host Responses ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Mesenteric Lymph

ABSTRACTA lack of appropriate disease models has limited our understanding of the pathogenesis of persistent enteric infections withMycobacterium aviumsubsp.paratuberculosis. A model was developed for the controlled delivery of a defined dose ofM. aviumsubsp.paratuberculosisto surgically isolated ileal segments in newborn calves. The stable intestinal segments enabled the characterization of host responses to persistentM. aviumsubsp.paratuberculosisinfections after a 9-month period, including an analysis of local mucosal immune responses relative to an adjacent uninfected intestinal compartment.M. aviumsubsp.paratuberculosisremained localized at the initial site of intestinal infection and was not detected by PCR in the mesenteric lymph node.M. aviumsubsp.paratuberculosis-specific T cell proliferative responses included both CD4 and γδ T cell receptor (γδTcR) T cell responses in the draining mesenteric lymph node. The levels of CD8+and γδTcR+T cells increased significantly (P< 0.05) in the lamina propria, andM. aviumsubsp.paratuberculosis-specific tumor necrosis factor alpha (TNF-α) and gamma interferon secretion by lamina propria leukocytes was also significantly (P< 0.05) increased. There was a significant (P< 0.05) accumulation of macrophages and dendritic cells (DCs) in the lamina propria, but the expression of mucosal toll-like receptors 1 through 10 was not significantly changed byM. aviumsubsp.paratuberculosisinfection. In conclusion, surgically isolated ileal segments provided a model system for the establishment of a persistent and localized entericM. aviumsubsp.paratuberculosisinfection in cattle and facilitated the analysis ofM. aviumsubsp.paratuberculosis-specific changes in mucosal leukocyte phenotype and function. The accumulation of DC subpopulations in the lamina propria suggests that further investigation of mucosal DCs may provide insight into host responses toM. aviumsubsp.paratuberculosisinfection and improve vaccine strategies to preventM. aviumsubsp.paratuberculosisinfection.

scholarly journals Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas

2020 ◽  
Author(s):  
Nancy G. Casanova ◽  
Manuel L Gonzalez-Garay ◽  
Belinda Sun ◽  
Christian Bime ◽  
Kenneth S. Knox ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Immunological Response ◽  
Functional Enrichment ◽  
Genomic Biomarkers ◽  
Diagnosis And Prognosis ◽  
Genomic Markers ◽  
Affected Tissue ◽  
Granulomatous Diseases

Abstract Rationale: Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures. Objective: To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis). Methods: Transcriptomic profiles of immune-related gene from micro-dissected lungs and mediastinal lymph nodes sarcoidosis granulomas was compared to infectious granulomas. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways. Results: Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers, excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, CXCL2, FABP4 . Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level. Conclusion : These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in two commonly affected tissue in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.

scholarly journals Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas

2020 ◽  
Author(s):  
Nancy G. Casanova ◽  
Manuel L Gonzalez-Garay ◽  
Belinda Sun ◽  
Christian Bime ◽  
Kenneth S. Knox ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Immunological Response ◽  
Functional Enrichment ◽  
Genomic Biomarkers ◽  
Diagnosis And Prognosis ◽  
Genomic Markers ◽  
Affected Tissue ◽  
Granulomatous Diseases

Abstract Rationale: Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures.Objective: To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis). Methods: Transcriptomic profiles of immune-related gene from micro-dissected lungs and mediastinal lymph nodes sarcoidosis granulomas was compared to infectious granulomas. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways. Results: Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers, excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, CXCL2, FABP4. Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level.Conclusion: These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in two commonly affected tissue in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.

Prognostic significance of lymph node dissection on stage-specific survival for patients with primary small intestine tumor treated with enterectomy: A population-based study, 2004-2015

2020 ◽  
Author(s):  
Yifei Chen ◽  
Fei He ◽  
Dan Guo ◽  
Yarui Li ◽  
Ruhua Wang ◽  
...  
Keyword(s):  
Small Intestine ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Cox Regression ◽  
Cox Model ◽  
Prognostic Significance ◽  
Survival Curves ◽  
Small Bowel Tumors ◽  
Kaplan Meier ◽  
Better Than

Abstract Background: The positive rate of lymph node detection(LND) can be used as a predictor of prognosis for patients undergoing radical resection of small bowel tumors; thorough local LND may be crucial for the accurate staging and management of the disease.The purpose of our study was to determine the effect of the LND in specific stages. Methods: This study included 5413 patients with primary small intestine tumors after enterectomy within SEER database from 2004-2015. A multivariable COX model and Kaplan-Meier plots survival curves were used to analyze survival.Results: Of the 5413 patients, 4675(86.4%) underwent lymphadenectomy, and 3896(72.0%) were moved 4 or more than 4 lymph nodes. LND was performed in 67.8%, 83.3%, 87.9%, 89.3% in pT1/2/3/4 disease. In multivariable Cox regression analyses, LND was associated with OS and CSS, and the extended LND are better than limited LND (all P<0.05 except pT2). Kaplan-Meier plots survival curves showed that LND can benefit patients.Conclusions: The removal of LND with 4 or more lymph nodes in pT1/3/4 patients has relatively obvious benefits for survival. The effect of LND with more lymph nodes is significantly better than limited LND. For pT1, pT3 and pT4, LND can be considered.

scholarly journals A Case of DisseminatedMycobacterium aviumInfection in a Dog in Greece

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
V. Kontos ◽  
E. I. Papadogiannakis ◽  
G. Mantziaras ◽  
M. Styliara ◽  
S. Kanavaki
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Mycobacterium Avium ◽  
Fine Needle Aspiration ◽  
Bacterial Culture ◽  
Pcr Amplification ◽  
Needle Aspiration ◽  
Molecular Techniques ◽  
Fine Needle ◽  
Pcr Products

A Basset Hound dog was presented with anorexia, fever, diarrhea, significant level of splenomegaly, and enlargement of mesenteric and superficial lymph nodes. Cytology of fine-needle-aspiration material, obtained from popliteal lymph node, revealed macrophages with intracytoplasmic, nonstaining, slender, rod-like structures, indicative of mycobacteria. Bacterial culture of lymph node aspirated material produced a colony which by means of molecular techniques (PCR amplification and hybridization of PCR products) was subsequently identified asMycobacterium avium. This is the first report of disseminatedM. aviuminfection in a dog in Greece.

RA02.01: COMPARISON OF THREE-FIELD VERSUS TWO-FIELD LYMPHADENECTOMY FOR THORACIC MIDDLE AND LOWER ESOPHAGEAL CANCER: POST-OPERATIVE RESULTS OF A RANDOMIZED CONTROLLED TRIAL

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 19-20
Author(s):  
Bin Li ◽  
Jiaqing Xiang ◽  
Yawei Zhang ◽  
Jie Zhang ◽  
Yihua Sun ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Lymph Node ◽  
Postoperative Complications ◽  
Lymph Nodes ◽  
Conflicts Of Interest ◽  
Tumor Staging ◽  
Operating Time ◽  
Thoracic Esophageal Cancer ◽  
Term Survival

Abstract Background Patients with esophageal cancer can benefit from extended lymphadenectomy. However, the role of 3-field lymphadenectomy is unclear, and the extent of lymphadenectomy for thoracic esophageal cancer is still under discussion. Methods From June 2013 to November 2016, 400 patients with middle and lower thoracic esophageal cancer were randomly assigned to receive 3-field (3FL, n = 200) or the 2-field (2FL, n = 200) lymphadenectomy. The postoperative complications, according to the Clavien-Dindo classification, and lymph node metastasis were compared on the basis of intention-to-treat principle. Results Baseline characteristics were balanced between the 2 arms. There were 187 patients (93.5%) had squamous cell carcinoma in 3FL arm, and 192 (96.0%) in the 2FL arm, P = 0262. According to the pathological reports, T staging in the 2 arms were comparable, however more N3 patients in the 3FL arm (10.5%, 21/200) than that in the 2FL arm (10%, 5/200), P = 0040. Consequently, less TNM staging I patients in the 3FL arm (16.0%, 32/200) than that in the 2FL arm (25.5%, 51/200), P = 0.019. Operating time was significantly longer in the 3FL arm (median, 183 vs. 168 [2FL] minutes, P < 0.001). Six patients in the 3FL arm (3%, 6/200) had reintubation, whereas no reintubation in the 2 FL arm (0%, 0/200), P = 0.030. Other postoperative complications were comparable in the 2 arms. One patient in the 2-field arm died of chyloperitoneum. According to the Clavien-Dindo classification of surgical complications, the distribution of severity were similar between the 2 arms, P = 0.416. More lymph nodes were resected in the 3FL arm (Median, 37 vs. 24 [2FL], P < 0.001). Lymph nodes resected in the mediastinum and upper abdomen were comparable between the 2 arms. 44 patients (22%) in the 3FL arm had positive lymph nodes. Conclusion Compared with 2-field lymphadenectomy, 3-field lymphadenectomy doesn’t increase the surgical risks for patients with thoracic esophageal cancer. 3-field lymphadenectomy can be performed safely, removing unforeseen cervical positive lymph node, and offering more accurate tumor staging. Long-term survival analysis under protocol will clarify the role of 3-field lymphadenectomy for esophageal cancer. Disclosure All authors have declared no conflicts of interest.

scholarly journals TRANSHIATAL ESOPHAGECTOMY IN SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS: WHAT ARE THE BEST INDICATIONS?

2020 ◽  
Vol 33 (4) ◽  
Author(s):  
Felipe Monge VIEIRA ◽  
Marcio Fernandes CHEDID ◽  
Richard Ricachenevsky GURSKI ◽  
Carlos Cauduro SCHIRMER ◽  
Leandro Totti CAVAZZOLA ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Cell Carcinoma ◽  
Neoadjuvant Therapy ◽  
Squamous Cell ◽  
Operative Time ◽  
Transhiatal Esophagectomy ◽  
Term Survival

ABSTRACT Background: Southern Brazil has one of the highest incidences of esophageal squamous cell carcinoma in the world. Transthoracic esophagectomy allows more complete abdominal and thoracic lymphadenectomy than transhiatal. However, this one is associated with less morbidity. Aim: To analyze the outcomes and prognostic factors of squamous esophageal cancer treated with transhiatal procedure. Methods: All patients selected for transhiatal approach were included as a potentially curative treatment and overall survival, operative time, lymph node analysis and use of neoadjuvant therapy were analyzed. Results: A total of 96 patients were evaluated. The overall 5-year survival was 41.2%. Multivariate analysis showed that operative time and presence of positive lymph nodes were both associated with a worse outcome, while neoadjuvant therapy was associated with better outcome. The negative lymph-node group had a 5-year survival rate of 50.2%. Conclusion: Transhiatal esophagectomy can be safely used in patients with malnutrition degree that allows the procedure, in those with associated respiratory disorders and in the elderly. It provides considerable long-term survival, especially in the absence of metastases to local lymph nodes. The wider use of neoadjuvant therapy has the potential to further increase long-term survival.

Sign in / Sign up

Export Citation Format

Share Document