- Inflammatory Bowel Disease
- Microscopic Colitis
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Asthma and respiratory diseases
- Pediatric health and respiratory diseases
- Sphingolipid Metabolism and Signaling
- Cell Adhesion Molecules Research
- RNA Research and Splicing
- Neonatal Respiratory Health Research
- Monoclonal and Polyclonal Antibodies Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- COVID-19 Clinical Research Studies
- Cancer-related molecular mechanisms research
- SARS-CoV-2 and COVID-19 Research
- Vasculitis and related conditions
- Bone Metabolism and Diseases
- Sarcoidosis and Beryllium Toxicity Research
- Long-Term Effects of COVID-19
- Enterobacteriaceae and Cronobacter Research
- Colorectal Cancer Treatments and Studies
- Immune Cell Function and Interaction
- Intraperitoneal and Appendiceal Malignancies
- Occupational exposure and asthma
- T-cell and B-cell Immunology
- Inflammasome and immune disorders
Genentech
2015
Medical College of Wisconsin
2007
Etrolizumab is a humanised monoclonal antibody that selectively binds the β7 subunit of heterodimeric integrins α4β7 and αEβ7. We aimed to assess etrolizumab in patients with moderately-to-severely active ulcerative colitis.In this double-blind, placebo-controlled, randomised, phase 2 study, colitis who had not responded conventional therapy were recruited from 40 referral centres 11 countries. Eligible (aged 18-75 years; Mayo Clinic Score [MCS] 5 higher [or ≥6 USA]; disease extending 25 cm...
Etrolizumab is a humanized monoclonal antibody against the β7 integrin subunit that has shown efficacy vs placebo in patients with moderate to severely active ulcerative colitis (UC). Patients colon tissues expressed high levels of αE gene (ITGAE) appeared have best response. We compared differences colonic expression ITGAE and other genes between who achieved clinical remission etrolizumab those did.We performed retrospective analysis data collected from 110 UC participated phase 2...
In Crohn's disease (CD), clinical symptoms correspond poorly to inflammatory activity. Biomarkers reflective of mucosal and bowel wall inflammation would be useful monitor The EMBARK study evaluated activity in patients with ulcerative colitis (UC) CD, used endoscopy or without cross-sectional imaging for biomarker discovery.UC (n=107) CD (n=157) were characterized underwent ileocolonoscopy (ICO). A subset (n=66) also computed tomography enterography (CTE). ICO CTE scored by a...
The αEβ7 integrin is crucial for retention of T lymphocytes at mucosal surfaces through its interaction with E-cadherin. Pathogenic or protective functions these cells during human intestinal inflammation, such as ulcerative colitis [UC], have not previously been defined, understanding largely derived from animal model data. Defining this phenotype in samples important UC pathogenesis and translational importance therapeutic targeting αEβ7–E-cadherin interactions. αEβ7+ αEβ7− colonic cell...
Chronic mucus hypersecretion (CMH) is a common feature in chronic obstructive pulmonary disease (COPD) and associated with worse prognosis quality of life. This study aimed to identify microRNA (miRNA)–mRNA regulatory networks underlying CMH. The expression profiles miRNA mRNA bronchial biopsies from 63 COPD patients were CMH using linear regression. Potential targets each CMH-associated identified Pearson correlations. Gene set enrichment analysis (GSEA) STRING (search tool for the...
Non-small cell lung carcinoma (NSCLC) is promoted by the increased activities of several small GTPases, including K-Ras4B, Rap1A, Rap1B, RhoC, and Rac1. SmgGDS an unusual guanine nucleotide exchange factor that activates many these thus may promote NSCLC development or progression. We report here protein levels are elevated in tumors, compared with normal tissue from same patients individuals without cancer. To characterize functions NSCLC, we tested effects silencing expression transfecting...
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with significant mortality. Prognostic biomarkers to identify rapid progressors are urgently needed improve patient management. Since the lysophosphatidic acid (LPA) pathway has been implicated in lung preclinical models and identified as potential therapeutic target, we aimed investigate if bioactive lipid LPA species could be prognostic that predict IPF progression. LPAs lipidomics were measured baseline placebo plasma of...
Abstract Background The recent outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has led to a worldwide pandemic. A subset COVID-19 patients progresses disease, with high mortality and limited treatment options. Detailed knowledge expression regulation genes required for viral entry into epithelial cells is urgently needed. Methods Here we assess patterns SARS-CoV-2 cells, their by genetic, epigenetic environmental...
The receptor for advanced glycation end products (RAGE) and Toll-like 4 (TLR4) is implicated in COPD. Although these receptors share common ligands signalling pathways, it not known whether they act concert to drive pathological processes We examined the impact of RAGE and/or TLR4 gene deficiency a mouse model COPD also determined expression correlates with airway neutrophilia hyperresponsiveness (AHR) patients.We measured inflammation AHR wild-type, RAGE-/- , TLR4-/- mice following acute...
BACKGROUND. Baseline expression of FCRL5, a marker naive and memory B cells, was shown to predict response rituximab (RTX) in rheumatoid arthritis. This study investigated baseline FCRL5 as potential biomarker clinical RTX granulomatosis with polyangiitis (GPA) microscopic (MPA).
Lysophospholipids are bioactive signaling molecules derived from cell membrane glycerophospholipids or sphingolipids and highly regulated under normal physiological conditions. Lysophosphatidic acids (LPAs) a class of lysophospholipids that act on G-protein-coupled receptors to exert variety cellular functions. Dysregulation phospholipase activity consequently LPA synthesis in serum have been linked inflammation, such as seen chronic obstructive pulmonary disease (COPD). The accurate...
Abstract Background Chronic obstructive pulmonary disease (COPD) exacerbations are heterogenous and profoundly impact the trajectory. Bioactive lipid lysophosphatidic acid (LPA) has been implicated in airway inflammation but significance of LPA COPD exacerbation is not known. The aim study was to investigate utility serum species (LPA16:0, 18:0, 18:1, 18:2, 20:4) as biomarkers exacerbation. Patients methods were measured baseline placebo sera a randomized controlled trial. Tertile levels...
Abstracts of the 9 th Congress ECCO European Crohn's and Colitis Organisation S7 (biventricular heart dysfunction sepsis) that occurred between wks 54 104.Conclusions: These data continue to support a positive benefit/ risk profile for GLM in treatment moderate severe UC; up 2 y maintained clinical benefit including reduction corticosteroid use.No new safety signals were observed with continued through wk 104; was similar 54.
COPD exacerbations are heterogeneous and can be triggered by bacterial, viral, or noninfectious insults. Exacerbations also in neutrophilic eosinophilic inflammatory responses. A noninvasive peripheral biomarker of characterised bacterial/neutrophilic inflammation is lacking. Granulocyte-colony stimulating factor (G-CSF) a key cytokine elevated during bacterial infection mediates survival, proliferation, differentiation function neutrophils.We hypothesised that high G-CSF would indicative...
<b>More DEGs are detected by RNA-Seq than microarrays in COPD lung biopsies and associated with immunological pathways. Performing bulk tissue cell-type deconvolution microarray samples, using the SVR method, reflects results.</b>https://bit.ly/2N8sY3s
Current knowledge about the respiratory microbiome is mainly based on 16S ribosomal RNA gene sequencing. Newer sequencing approaches, such as metatranscriptomics, offer technical ability to measure viable response environmental conditions smoking well explore its functional role by investigating host-microbiome interactions. However, feasibility in research, especially lung biopsies, still very limited. was performed bronchial biopsies from clinically stable smokers (n = 5) and ex-smokers 6)...