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Biomedical subjects

C M Thompson

Publications and source records attributed to C M Thompson.

96 records · Page 6Linked to original sources
PubMedDate not supplied

Kinetics of the postinhibitory reactions of acetylcholinesterase poisoned by chiral isomalathion: a surprising nonreactivation induced by the RP stereoisomers.

Inhibitory (ki), spontaneous (k0), and oxime-mediated reactivation (k(oxime)) reaction kinetics for the four stereoisomers of isomalathion (SPRC,SPSC,RPRC, and RPSC) were determined against rat brain acetylcholinesterase (AChE). (SPRC)-Isomalathion was the most potent anticholinesterase agent and RPSC-isomalathion the least potent with racemic material approximately midway in activity. Following inhibition of rat brain AChE by (SPRC)- or (SPSC)-isomalathion, k0 and k(oxime) values were obtained that were comparable to (SP)-isoparathion methyl, indicating that the same mechanism of inhibition was shared, namely, formation of an O,S-dimethyl phosphorothiolated enzyme. Conversely, no appreciable reactivation occurred with or without oxime following inhibition of rat brain AChE by (RPSC)- or (RPRC)-isomalathion. This observation was not consistent with (RP)-isoparathion methyl, and a switch in inhibition mechanism to the loss of the thiomethyl moiety is suggested. The nonreactivation of rat brain AChE following inhibition by the (RP)-isomalathion stereoisomers is postulated to result from a mechanism involving either a beta-elimination of diethyl fumarate or displacement of the thiosuccinate moiety from the phosphate moiety.

Acetylcholinesterase↗
PubMedDate not supplied

Synthesis, absolute configuration, and analysis of malathion, malaoxon, and isomalathion enantiomers.

Syntheses of the enantiomers of malathion, malaoxon, and isomalathion are reported herein. Malathion enantiomers were prepared from (R)- or (S)-malic acid in three steps. Enantiomers of malathion were converted to the corresponding enantiomers of malaoxon in 52% yield by oxidation with monoperoxyphthalic acid, magnesium salt. The four isomalathion stereoisomers were prepared via two independent pathways using strychnine to resolve the asymmetric phosphorus moiety. The absolute configurations of the four stereoisomers of isomalathion were determined by X-ray crystallographic analysis of an alkaloid salt precursor. A high-performance liquid chromatography technique was developed to resolve the four stereoisomers of isomalathion, and to determine their stereoisomeric ratios.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Interaction of acetylcholinesterase with the enantiomers of malaoxon and isomalathion.

The biomolecular reaction constants (ki), dissociation constants (Kd), and phosphorylation constants (kp) were determined for the enantiomers of malaoxon against rat brain acetylcholinesterase, and for the stereoisomers of isomalathion against rat brain acetylcholinesterase and electric eel acetylcholinesterase. (R)-Malaoxon was an 8.6-fold more potent anti-cholinesterase than (S)-malaoxon. Isomalathion stereoisomers with the R configuration at carbon were 3-13-fold stronger inhibitors than those with the S configuration. The isomalathion stereoisomers with the R configuration at phosphorus were 4.3-8.8-fold stronger inhibitors of rat brain acetylcholinesterase, yet 3.4-5.8-fold weaker inhibitors of electric eel acetylcholinesterase, than the isomalathion stereoisomers with the S configuration at phosphorus. The rat brain acetylcholinesterase spontaneous (k0 = approximately 13.0 x 10(-3) min-1) and oxime-mediated (koxime) = 51.0 x 10(-3) min-1) reactivation rate constants following inhibition by isomalathion stereoisomers with the R configuration at phosphorus were comparable to spontaneous (11.3 x 10(-3) min-1) and oxime-mediated (50.2 x 10(-3) min-1) reactivation rates obtained for (S)-isoparathion methyl. These data support a common phosphorylation mechanism, namely, the displacement of the thiosuccinyl moiety from isomalathion stereoisomers with the R configuration at phosphorus, and displacement of the p-nitrophenoxy ligand from (S)-isoparathion methyl to form the same O,S-dimethyl phosphorothiolated enzyme. Rat brain acetylcholinesterase inhibited by the isomalathion stereoisomers with the S configuration at phosphorus were refractory to reactivation, suggesting an alternate mechanism of inhibition, i.e., the loss of the methylthio ligand. Several mechanisms are proposed to account for the subsequent nonreactivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗
PubMedDate not supplied

Epidemic of meningitis and febrile illness in neonates caused by ECHO type 11 virus in Philadelphia.

Between April and November, 1980, an outbreak of meningitis and of febrile illness of neonates caused by ECHO 11 virus occurred in Philadelphia and surrounding communities. Thirty-eight virologically confirmed and ten virologically presumptive cases of meningitis were hospitalized in two Philadelphia hospitals for children. Most patients had fever and irritability. Vomiting, upper respiratory symptoms and poor feeding were present in one-third to one-half of the cases. Seventy-five percent of cases occurred between June 10 and August 18. The number of males and females was similar; 71% of children were 4 months of age or younger. This out break differed from those previously reported on enteroviruses in general, and on ECHO 11 virus in particular, in that no strong male predominance occurred and the patients were younger. A minimum attack rate of 4.1 per 1000 Philadelphia resident children ages 1 day to 4 months was estimated.

Adolescent↗
PubMedDate not supplied

Cosegregation of the Tnfalpha locus with cardiovascular phenotypes in the F2 generation of a New Zealand genetically hypertensive and Brown Norway cross.

1. The association of the Tnfalpha locus with several cardiovascular phenotypes and body mass has been studied in the F2 generation of a reciprocal cross between rats of the New Zealand genetically hypertensive (GH) and the normotensive Brown Norway (BN) strains. In the total F2 population the GH allele of Tnfalpha cosegregated with increased intra-arterial blood pressure (BP) in a recessive manner. A similar but weaker effect was observed for tail BP. 2. An association between genotype and body mass in females with GH grandfathers was also detected. 3. An association between genotype and pulse rate was observed for females. 4. This work supports other evidence pointing to an association of a gene (or genes) on rat chromosome 20 with hypertension.

Animals↗