Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reverse transcription polymerase chain reaction (RT-PCR) single-strand conformation polymorphism analysis was used to detect topoisomerase I (top1) mutations in total RNA from 16 specimens that were excised during surgery from eight patients with non-small cell lung cancer (NSCLC) who had received preoperative chemotherapy consisting of irinotecan (CPT-11) and cisplatin. PCR single-strand conformation polymorphism and subsequent DNA sequencing analysis showed two nucleotide substitutions resulting in Trp736stop (TGG to TGA) and Gly737Ser (GGT to AGT) in one tumor specimen. The mutations were located near a site in top1 that was previously reported to harbor a mutation in the human lung cancer cell line PC7/CPT, which was selected for CPT resistance. These results demonstrate that mutations in top1 occur after chemotherapy with CPT-11 in NSCLC patients and suggest that development of resistance to CPT-11 in some patients may involve mutation of top1. However, the significance of top1 mutations to CPT resistance needs to be further investigated.
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PMID:Point mutations in the topoisomerase I gene in patients with non-small cell lung cancer treated with irinotecan. 1184 5

A number of data are consistent with the hypothesis that increases in intracellular Na+ concentration (Na+i) during ischemia and early reperfusion lead to calcium overload and exacerbation of myocardial injury. However, the mechanisms underlying the increased Na+i remain unclear. 23Na nuclear magnetic resonance spectroscopy was used to monitor Na+i in isolated rat hearts perfused with a high concentration of fatty acid as can occur under some pathological conditions. Whole-cell patch-clamp experiments were also performed on isolated cardiomyocytes in order to investigate the role of voltage-gated sodium channels. Na+i increased to substantially above control levels during no-flow ischemia. The results show that a pharmacological reduction of Na+i increase by cariporide (1 micromol/L, a Na+/H+ exchange blocker) is not the only protection against ischemia-reperfusion damage, but that such protection may also be brought about by metabolic action aimed at reducing fatty acid utilization by myocardial cells. This action was obtained in the presence of etomoxir (0.1 micromol/L), an inhibitor of carnitine palmitoyltransferase-1 (the key enzyme involved in fatty acid uptake by the mitochondria) which also decreases long-chain acyl carnitine accumulation. The possibility of Na+ channels participating in Na+i increase as a consequence of alterations in cardiac metabolism was studied in isolated cells. Sustained I(Na) was stimulated by the presence of lysophosphatidylcholine (LPC, 10 micromol/L) whose accumulation during ischemia is, at least partly, dependent on increased long-chain acyl carnitine. Current activation was particularly significant in the range of potentials between -60 and -20 mV. This may have particular relevance in ischemia. The quantity of charge carried by sustained I(Na) was reduced by 24% in the presence of 1 micromol/L cariporide. Therefore, limitation of long-chain fatty acid metabolism, and consequent limitation of ischemia-induced long-chain acyl carnitine accumulation, may contribute to reducing intracellular Na+ increase during ischemia-reperfusion.
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PMID:Different pathways for sodium entry in cardiac cells during ischemia and early reperfusion. 1261 73

The attention deficit/hyperactivity disorder (ADHD) shows an increased prevalence in arrested offenders compared to the normal population. The aim of the present study was to investigate whether ADHD symptoms are a major risk factor for criminal behaviour, or whether further deficits, mainly abnormalities in emotion-processing, have to be considered as important additional factors that promote delinquency in the presence of ADHD symptomatology. Event related potentials (ERPs) of 13 non-delinquent and 13 delinquent subjects with ADHD and 13 controls were compared using a modified visual Go/Nogo continuous performance task (VCPT) and a newly developed version of the visual CPT that additionally requires emotional evaluation (ECPT). ERPs were analyzed regarding their topographies and Global Field Power (GFP). Offenders with ADHD differed from non-delinquent subjects with ADHD in the ERPs representing higher-order visual processing of objects and faces (N170) and facial affect (P200), and in late monitoring and evaluative functions (LPC) of behavioural response inhibition. Concerning neural activity thought to reflect the allocation of neural resources and cognitive processing capability (P300 Go), response inhibition (P300 Nogo), and attention/expectancy (CNV), deviances were observable in both ADHD groups and may thus be attributed to ADHD rather than to delinquency. In conclusion, ADHD symptomatology may be a risk factor for delinquency, since some neural information processing deficits found in ADHD seemed to be even more pronounced in offenders with ADHD. However, our results suggest additional risk factors consisting of deviant higher-order visual processing, especially of facial affect, as well as abnormalities in monitoring and evaluative functions of response inhibition.
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PMID:Neurophysiological correlates of delinquent behaviour in adult subjects with ADHD. 2224 45