ORGAN-CULTURED AIRWAY EXPLANTS: A NEW MODEL OF AIRWAY HYPERRESPONSIVENESS
Bibliographic record
Abstract
Respiratory pathology research is limited by the number of appropriate multicellular models suitable for studying mechanical properties and signaling pathways that are involved in airway responsiveness. In this study, the electrophysiological and pharmacomechanical properties of organ-cultured explants derived from normal guinea pig bronchi and trachea were investigated. The explants maintained their basic histological phenotype but became hyperreactive to excitatory (muscarinic, histaminergic, serotinergic, and thromboxane receptor agonists, 60 mM KCl) and inhibitory (norepinephrine, isoproterenol) stimuli within the first 3 days in culture, with or without serum in the culture medium. Indomethacin pretreatment did not modify the spasmogen responses of the explant. The onset of this intrinsic overreactivity was highly dependent on the initial presence of epithelium, took 3 days to reach its maximum, and lasted over several days (days 3 to 7). Removal of Ca2+ from the bathing solution initially normalized the inotropic responses of the cultured versus freshly isolated airway tissues. However, the responses to repetitive carbachol challenges in the absence of Ca2+ displayed a slower inactivation in the cultured explants compared to fresh tissues. Smooth muscle resting membrane potential and potassium-induced depolarizations were unaffected by organ culture. Immunohistochemical analyses revealed the presence of apoptotic bodies in the submucosa and epithelial layers, but none in the smooth muscle layer of cultured airways. These functional and histological findings may prove useful in understanding signaling processes involved in tissue hyperresponsiveness related to asthma.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.001 | 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".