This study was designed to compare the activity of skeletal muscle carnitine palmitoyltransferase I (CPT I) in trained and inactive men (n = 14) and women (n = 12). CPT I activity was measured in intact mitochondria, isolated from needle biopsy vastus lateralis muscle samples ( approximately 60 mg). The variability of CPT I activity determined on two biopsy samples from the same leg on the same...

Irinotecan [7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11)] is a promising water-soluble analogue of camptothecin [S. Sawada et al., Chem. & Pharm. Bull. (Tokyo), 39: 1446-1454, 1991]. We have reported previously the presence of an important polar metabolite, in addition to 7-ethyl-10-hydroxycamptothecin (SN-38) beta-glucuronide, in samples of plasma taken from patie...

The search for new water-soluble analogues of camptothecin (CPT) with higher activity and less toxicity has led to the development of a novel compound, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11), which showed significant antitumor activity against a broad spectrum of experimental tumor models by i.p., i.v., or oral administration. When its activity against L1210...

Irinotecan (CPT-11) is an analogue of 20(S)-camptothecin with promising activity against several tumor types. In patients, CPT-11 is metabolized to 7-ethyl-10-hydroxycamptothecin (SN-38) and to the beta-glucuronide of SN-38. Recently, we identified an additional metabolite of CPT-11, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin (APC; L. P. Rivory et al. , Cancer...

Biotransformation of irinotecan (CPT-11) into its pharmacologic active metabolite SN-38 was investigated in patients treated for advanced colorectal cancer. A dose of 180 mg/m(2) CPT-11 was administered to 6 patients by 60 min hepatic intra-arterial infusion (HAI) via a surgically implanted Port-a-Cath® system. Blood samples were collected from 0 to 360 min after start of HAI, and CPT-11 plus m...

The replication fork temporarily stalls when encountering an obstacle on the DNA, and replication resumes after the barrier is removed. Simultaneously, activation of the replication checkpoint delays the progression of S phase and inhibits late origin firing. Camptothecin (CPT), a topoisomerase I (Top1) inhibitor, acts as a DNA replication barrier by inducing the covalent retention of Top1 on D...

It has been reported that sodium cholate can separate the catalytic component of carnitine palmitoyltransferase-I (CPT-I) from a putative malonyl-CoA-binding regulatory protein capable of conferring sensitivity to malonyl-CoA on CPT-II. We found that cholate preferentially extracted a contaminating malonyl-CoA-sensitive CPT from mitochondrial inner membranes. When cholate extracts of outer memb...

The effects of endurance training on PGE (2) levels and upon the maximal activity of hepatic carnitine palmitoyltransferase (CPT) system were studied in rats bearing the Walker 256 carciosarcoma. Animals were randomly assigned to a sedentary control (SC), sedentary tumor-bearing (ST), exercised control (EC), and as an exercised tumor-bearing (ET) group. Trained rats ran on a treadmill (60% VO (...

This paper explores a tree kernel-based method for nominal semantic role labeling (SRL). In particular, a new dependency-driven constituent parse tree (D-CPT) structure is proposed to better represent the dependency relations in a CPT-style structure, which employs dependency relation types instead of phrase labels in CPT. In this way, D-CPT not only keeps the dependency relationship informatio...

Invariance under the combined transformations of CPT (in any order) is guaranteed in Quantum Field Theory in flat space times due to a basic theorem (CPT Theorem). The currently used formalism of particle physics phenomenology is based on this theorem. However, there may be violations of the basic underlying assumptions of this theorem in models of quantum gravity, namely Lorentz covariance, un...