Time-dependent toxicity of sulfonamide reactive metabolites in cells of patients with sulfonamide hypersensitivity
Bibliographic record
Abstract
Background Sulfonamide hypersensitivity is a major clinical problem for many patients and the mechanisms remain largely unknown. We have previously identified altered response to reactive drug metabolites as an important component of drug hypersensitivity. Methods Peripheral blood mononuclear cells from patients with a history of sulfonamide hypersensitivity (n=6) and normal controls (n=6) were incubated with increasing concentrations of sulfamethoxazole and sulfamethoxazole hydroxylamine over time with determinations of cell viability every 6 hours up to 36 hours. Cell viability was determined using an MTT method and the degree of apoptosis determined using FACS. Results A time-dependent decrease in viability was seen in the cells of both controls and patients, with significantly more cell death (p>0.05) seen in the cells of patients than controls after 12 hours of incubation (p>0.05). This was associated with a significant increase in cell death related to necrosis in the cells of patients (p>0.01) versus controls at time 24 hours. Conclusions Time-related delays in differential cellular sensitivity to reactive drug metabolites and differential mechanisms of cell death suggest that there are alterations in the ability of the cells of susceptible individiuals to respond that limits the ability of these cells to deal with reactive drug metabolites. Possible cellular mechanism(s) include may include altered ability to deal with reactive species. Clinical Pharmacology & Therapeutics (2004) 75, P26–P26; doi: 10.1016/j.clpt.2003.11.097
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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 | 0.001 |
| 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".