Bibliographic record
Abstract
The leukotrienes are eicosanoids, derived from a cell membrane phospholipid constituent arachidonic acid, which is selectively cleaved by phospholipase A 2 from cell membranes. Arachidonic acid is converted sequentially to 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and then to leukotriene A 4 (LTA 4 ) by a catalytic complex consisting of 5-lipoxygenase (5LO) and the 5-lipoxygenase-activating protein (FLAP). In the presence of leukotriene-C 4 synthase, glutathione is adducted at the C-6 position of LTA 4 to yield the molecule known as LTC 4 , which is exported from the cytosol to the extracellular microenvironment, where the glutamic acid moiety is cleaved to form LTD 4 . Cleavage of the glycine moiety from LTD 4 results in the formation of LTE 4 , which is the stable excretory product. LTC 4 , LTD 4 , and LTE 4 , are known as the cysteinyl leukotrienes; together these molecules constitute the material formerly known as the slow-reacting substance of anaphylaxis (SRS-A). All three cysteinyl leukotrienes have the same range of biological effects; however, LTE 4 is much less potent than its precursor molecules. Among the cells in the lung that possess the enzymatic activities to produce the cysteinyl leukotrienes are mast cells, eosinophils, and alveolar macrophages. There is, now, compelling information to implicate the cysteinyl leukotrienes as mediators of asthmatic bronchoconstriction. Increased production of the cysteinyl leukotrienes, as measured by increases in urinary excretion of LTE 4 , has been demonstrated after allergen inhalation (1, 2) in subjects with atopic asthma and during episodes of acute severe asthma (2). Also, subjects with aspirin-induced asthma have higher baseline levels of urinary LTE 4 when compared with other subjects with asthma (3); this level increases after aspirin ingestion, and is associated with an overexpression of LTC 4 synthase in airway biopsies (4). Treatment with drugs that inhibit the synthesis of the cysteinyl leukotrienes or block the CysLT 1 receptor, which mediates the action of the cysteinyl leukotrienes in the airways, markedly attenuates allergen-induced, aspirin-induced, and exercise-induced bronchoconstriction (5–7) and allergen-induced airway hyperresponsiveness (8), as well as improving spontaneous bronchoconstriction (9, 10), and other indices of asthma control (11). Taken together, these studies indicate an important role for the cysteinyl leukotrienes in causing bronchoconstriction.
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 | 0.002 | 0.007 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.003 | 0.005 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.006 | 0.004 |
| 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".