Tetrahydrobiopterin deficiency induces gastroparesis in newborn mice
Bibliographic record
Abstract
Pyloric stenosis, the most common infant gastrointestinal disease, has no known etiology and clinically presents as abnormal gastric emptying with evidence of pyloric muscle hypertrophy. Whether abnormalities in gastric muscle contraction and/or relaxation have a role in this condition is poorly known, but gastroparesis is commonly observed in association with delayed gastric emptying in adults. Therefore, we evaluated the tetrahydrobiopterin (BH4)-deficient newborn mouse model of this disease (hph-1) and hypothesized that their gastric muscle properties are impaired, when compared with wild-type control animals. In vitro studies evaluating the age-dependent gastric fundus muscle contraction and relaxation potential were conducted. Compared with wild-type mice, the hph-1 stomach content/body weight ratio was significantly increased in newborn but not juvenile or adult animals, confirming abnormal gastric emptying. Gastric tissue neuronal nitric oxide synthase (nNOS) protein expression was upregulated in both newborn and adult hph-1 mice, but in the former there was evidence of enzyme uncoupling and higher tissue superoxide generation when compared with same age-matched animals. As opposed to the lack of strain differences in the U46619-induced force, the newborn hph-1 gastric muscle carbachol-induced contraction and nNOS-dependent relaxation were significantly reduced (P < 0.01). These group differences were not present in juvenile or adult mice. Preincubation with BH4 significantly enhanced the newborn hph-1, but not wild-type, gastric muscle contraction. In conclusion, changes compatible with gastroparesis are present in the newborn mouse model of pyloric stenosis. The role of BH4 deficiency and possibly associated gastroparesis in the pathogenesis of infantile pyloric stenosis warrants further investigation.
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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 | 0.001 |
| 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".