Studies in the expression and modulation of mucosal addressin cell adhesion molecule-1 (MAdCAM-1)
Bibliographic record
Abstract
Introduction: The endothelial mucosal cell adhesion molecule (MAdCAM-1) is \nconsidered to be critically important in recruiting lymphocytes expressing the α4β7 cell \nsurface integrin. In addition to its well-characterised role in the normal gastrointestinal \ntract, there is emerging evidence of its role in liver and gastrointestinal inflammation. The \nability to detect MAdCAM-1 has thus far been challenging, hindering progress into studies \nto explore its modulation. \nAims: (i) To characterise MAdCAM-1 in the liver and gut, (ii) establish an in vitro \nmodel system of MAdCAM-1 and (iii) investigate the factors leading to its expression \nand subsequent modulation. \nMethods: I have described novel methods of detecting MAdCAM-1 by: \n1. Characterising its presence in the human liver, gut and associated tissues e.g. pancreas. \n2. Developing a reverse transcriptase–polymerase chain reaction (RT-PCR) technique so as \nto detect MAdCAM-1 in the gastrointestinal system and thus quantify its expression using \nReal-Time RT-PCR analysis. \n3. Developing an in vitro cell culture system using the endothelial SVEC4-10 cells to express \nand subsequently modulate the expression of MAdCAM-1. \nResults: Using immunohistochemical methodology I found that in end stage chronic liver \ndisease, MAdCAM-1 is expressed primarily on the peribiliary plexus and lymphoid \naggregates, where it may facilitate lymphocyte egress. MAdCAM-1’s constitutive \nexpression was confirmed in histologically normal gut tissue and its upregulation was \ndemonstrated in ulcerative colitis and Crohn’s disease, particularly localised to the venular \nendothelium of the lamina propria and follicular dendritic cells. MAdCAM-1 mRNA from \nhuman gut was measured by a RT-PCR technique in which a 94 base pair product \nconsistent with human mucosal vascular MAdCAM-1 was detected in normal large bowel. \nReal Time analysis confirmed that MAdCAM-1 was upregulated in end stage liver \ndisease. In a cell culture system MAdCAM-1 was shown to be upregulated by TNFα on \nSVEC4-10 using immunofluoresence studies and its expression was further modulated by \nsteroids and anti-sense oligonucleotides. \nConclusion: The importance of MAdCAM-1 in the gastrointestinal system is emphasised \nthroughout. Our in vitro culture system utilising the SVEC endothelial cell line provides \nthe basis for studying the modulation of MAdCAM-1 expression.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".