Leukotriene C4 synthase deficiency causes spontaneous emphysematous changes in mice
Bibliographic record
Abstract
Introduction: Emphysema is an important component of chronic obstructive pulmonary disease (COPD) for which effective therapies are lacking. Emphysema is proposed to be caused by chronic inflammation induced by noxious particles but is also associated with lung development. Cysteinyl-leukotrienes (LTC4, LTD4, and LTE4, cysLTs) are inflammatory lipid mediators derived from arachidonic acid and the cysLT1 receptor expression is reportedly increased in COPD patients with severe exacerbations. However, whether cysLT synthesis influence the development emphysema is unknown. Aim: To investigate the influence of the constitutive synthesis of cysLTs on lung structure. Methods: Lung structure and function were assessed in leukotriene C4 synthase knockout (LTC4S-KO) mice, ranging in age from 1-40 weeks, by the measurement of pulmonary mechanics using FlexiVent and the mean linear intercept (MLI), respectively. To examine the involvement of immune cells, differential cell counts in bronchoalveolar lavage (BAL) and immunohistochemistry of lung were performed. Emphysema-related molecules including protease/antiprotease expression were assessed by qPCR and ELISA. Results: Histological examination revealed premature emphysematous changes in the lungs, in evidence as early as 5 weeks of age. Static compliance and the K value (Salazar-Knowles equation) were higher and tissue elastance was lower in LTC4S-KO mice than in age matched wild type (WT) mice. Additionally, MLI was higher in LTC4S-KO mice. In BAL fluid from LTC4S-KO mice, hemosiderin-laden macrophages were increased. Conclusions: LTC4S deficiency in vivo leads to emphysematous changes spontaneously, and it may be caused by abnormal maturation of lung.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.008 | 0.003 |
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".