Bilateral pallidal stimulation for cervical dystonia: Dissociated pain and motor improvement
Bibliographic record
Abstract
Septic shock is a dangerous condition with high mortality rates. In sepsis, the inducible form of nitric oxide (NO) synthase is induced, releasing high amounts of NO. Glucocorticoids have potent anti-inflammatory properties and are very effective in inhibiting the induction of this enzyme if administered before the shock onset. It is known that glucocorticoid receptor (GR) has critical cysteine residues for steroid binding in its hormone-binding and DNA-binding domains. It has also been reported that NO reacts with —SH groups, forming<i>S</i>-nitrosothiols. Therefore, we examined the potential effect of NO on the ligand-binding ability of GR. NO donors (<i>S</i>-nitroso-acetyl-dl-penicillamine,<i>S</i>-nitroso-dl-penicillamine, or<i>S</i>-nitroso-glutathione) decreased, in a time- and dose-dependent manner, the binding of [<sup>3</sup>H]triamcinolone to immunoprecipitated GR from mouse L929 fibroblasts. The nonnitrosylated parent molecules,<i>N</i>-acetyl-dl-penicillamine, and reduced gluthatione were without effect. Scatchard plots revealed that the number of ligand binding sites and <i>K</i><sub>d</sub> were reduced (50%) by NO donors. Western blot analysis ruled out the possibility that dissociation of GR/heat shock protein 90 heterocomplex or decrease in GR protein would account for the inhibitory effect of NO. Decreased ligand binding to GR was found when NO donors were incubated with intact fibroblasts. Incubation with NO donors also decreased the steroid-induced reduction in [<sup>3</sup>H]uridine incorporation into RNA. All of these NO effects were inhibited by the thiol-protecting agent dithiothreitol. Therefore,<i>S</i>-nitrosylation of critical —SH groups in GR by NO with consequent decreases in binding and affinity may be the mechanisms which explain the failure of glucocorticoids to exert their anti-inflammatory effects in septic shock.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".