Function of cyclo‐oxygenase‐1 and cyclo‐oxygenase‐2 in the ductus arteriosus from foetal lamb: differential development and change by oxygen and endotoxin
Bibliographic record
Abstract
1. Prenatal patency of the ductus arteriosus is maintained mainly by prostaglandin(PG) E(2). Here we have examined the relative importance of cyclo-oxygenase-1 (COX1) and cyclo-oxygenase-2 (COX2) for PGE(2) formation in the foetal lamb ductus (0.65 gestation onwards). 2. Using fluorescence microscopy and immunogold staining, COX1 appeared more abundant than COX2 in endothelial and smooth muscle cells, and this difference was greater before-term. Inside muscle cells, COX1 and COX2 immunoreactivity was located primarily in the perinuclear region. Endotoxin, given to the lamb in utero (approximately 0.1 microg kg(-1)), caused COX2 upregulation, while an opposite effect with disappearance of the enzyme followed endotoxin treatment in vitro (100 ng ml(-1)). COX1 immunoreactivity remained virtually unchanged with either treatment; however, this isoform as well as any induced COX2 migrated towards the outer cytoplasm. 3. The COX2 inhibitor L-745,337 (1--10 microM) contracted the isolated ductus at term, the response being almost as high as that to indomethacin (dual COX1/COX2 inhibitor) over the same dose-range. Conversely, L-745,337 was relatively less effective in the premature. 4. Pretreatment of the premature in vivo with endotoxin enhanced the contraction of the ductus to L-745,337, while in vitro endotoxin had a variable effect. 5. The premature ductus exhibited a stronger contraction to L-745,337 following exposure to oxygen. On the other hand, the oxygen contraction, which is modest before-term, was enhanced by L-745,337. 6. We conclude that COX1 and COX2 develop unevenly in the ductus. While both enzymes contribute to PGE(2) formation at term, COX1 is the major isoform in the premature. COX2, however, may acquire greater importance before-term following physiological and pathophysiological stimuli.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".