Author
Stephen Brimijoin
Other affiliations: University of Minnesota, University of Nebraska Medical Center, University of Rochester ...read more
Bio: Stephen Brimijoin is an academic researcher from Mayo Clinic. The author has contributed to research in topics: Acetylcholinesterase & Butyrylcholinesterase. The author has an hindex of 47, co-authored 202 publications receiving 7402 citations. Previous affiliations of Stephen Brimijoin include University of Minnesota & University of Nebraska Medical Center.
Papers published on a yearly basis
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TL;DR: The generally high levels of BChE activity in tissues, including the motor endplate, and the observation that mice live without AChE, suggest that B ChE has an essential function in nullizygous mice and probably in wild‐type mice as well.
Abstract: We have described recently an acetylcholinesterase (AChE) knockout mouse. While comparing the tissue distribution of AChE and butyrylcholinesterase (BChE), we found that extraction buffers containing Triton X-100 strongly inhibited mouse BChE activity. In contrast, buffers with Tween 20 caused no inhibition of BChE. Conventional techniques grossly underestimated BChE activity by up to 15-fold. In Tween 20 buffer, the intestine, serum, lung, liver, and heart had higher BChE than AChE activity. Only brain had higher AChE than BChE activity in AChE +/+ mice. These findings contradict the dogma, based mainly on observations in Triton X-100 extracts, that BChE is a minor cholinesterase in animal tissues. AChE +/- mice had 50% of normal AChE activity and AChE -/- mice had none, but all mice had similar levels of BChE activity. BChE was inhibited by Triton X-100 in all species tested, except rat and chicken. Inhibition was reversible and competitive with substrate binding. The active site of rat BChE was unique, having an arginine in place of leucine at position 286 (human BChE numbering) in the acyl-binding pocket of the active site, thus explaining the lack of inhibition of rat BChE by Triton X-100. The generally high levels of BChE activity in tissues, including the motor endplate, and the observation that mice live without AChE, suggest that BChE has an essential function in nullizygous mice and probably in wild-type mice as well.
329 citations
TL;DR: The present work and previous computational studies strongly suggest that a low affinity THA peripheral site exists in AChE, and this peripheral site provides a structural basis for design of improved cholinesterase ligands for treating Alzheimer's disease and for other health-related purposes.
328 citations
TL;DR: The behavior of SPLI during ultracentrifugation of nerve and ganglion extracts indicated that this peptide was normally present both in a soluble form and in association with particles but was transported primarily in the latter form.
243 citations
TL;DR: The authors showed that AChE may play a role in pathogenesis of Alzheimer's disease at 9-12 months of the mouse's life, and that plaque onset in the hybrids occurred 30-50% sooner than in the parental lines.
185 citations
182 citations
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TL;DR: The present review focuses on the organisation of descending pathways and their pathophysiological significance, the role of individual transmitters and specific receptor types in the modulation and expression of mechanisms of descending inhibition and facilitation and the advantages and limitations of established and innovative analgesic strategies which act by manipulation of descending controls.
2,565 citations
TL;DR: It is concluded that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses, and fundamental changes in chemical testing and safety determination are needed to protect human health.
Abstract: For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from...
2,475 citations
TL;DR: Etude du mecanisme d'action des neurones sensoriels et des fonctions de leurs effecteurs locaux en reponse a differents stimuli, au niveau des tissus directement en contact avec l'environnement exterieur.
1,685 citations
01 Jan 1976
TL;DR: A positive temperature coefficient is the term which has been used to indicate that an increase in solubility occurs as the temperature is raised, whereas a negative coefficient indicates a decrease in Solubility with rise in temperature.
Abstract: A positive temperature coefficient is the term which has been used to indicate that an increase in solubility occurs as the temperature is raised, whereas a negative coefficient indicates a decrease in solubility with rise in temperature.
1,573 citations
TL;DR: With the present development of various new anticancer agents, it is recommended that alternative formulation approaches should be pursued to allow a better control of the toxicity of the treatment and the pharmacological interactions related to the use of CrEL.
1,546 citations