Pulmonary hypertension in the newborn GTP-cyclohydrolase 1 deficient mouse is unrelated to endothelium-dependent vasorelaxation potential
Bibliographic record
Abstract
Background: Tetrahydrobiopterin (BH4) is an endothelial nitric oxide (NO) synthase (eNOS) cofactor. Its absence results in eNOS uncoupling and a shift from NO to reactive oxygen species (ROS) generation. The hph-1 mouse is deficient in GTP-cyclohydrolase 1 (GCH1) production, resulting in lowered BH4 tissue content. The adult hph-1 mouse has pulmonary hypertension secondary to eNOS uncoupling, yet whether similar changes are evident in the newborn is presently unknown. Thus, we evaluated 1-3 day old newborn hph-1 pups and compared them to wild-type mice (C57BL/6xCBA). Methods and results: Lung morphometry, BH4 and its oxidized metabolite BH2 content were measured and near-resistance pulmonary arteries were studied. In control and hph-1 mice, the BH4 lung content is inversely proportional with age, but significantly lower in the mutated animals (P<0.01). Pulmonary hypertension is evident in the newborn hph-1 as an increase in the right ventricle-to-left-ventricle+septum ratio, compared with wild-type mice (P<0.05). In response to the thromboxane A2 analogue (U46619), the pulmonary arteries of hph-1 mice generate less force (P<0.01), when compared with controls, but show a similar vasorelaxant response to eNOS-dependent and -independent stimulation. As compared with wild-type, a significant increase in medial thickness of small pulmonary arteries is evident in the newborn hph-1 mice (P<0.05). Conclusion: Pulmonary hypertension is present from birth in the GCH1 deficient mice, not as a result of vasoconstriction, but secondary to pulmonary vascular remodeling.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".