Stephen Brimijoin

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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(More)
We report highly potent, selective, and low cost bifunctional acetylcholinesterase (AChE) inhibitors developed by our two-step prototype optimization strategy utilizing computer modeling of ligand docking with target proteins: 1) identify low affinity sites normally missed by x-ray crystallography; and 2) design bifunctional analogs capable of simultaneous(More)
Butyrylcholinesterase (BuChE) is increased in the cerebral cortex of Alzheimer's disease (AD) patients, particularly those carrying epsilon4 allele of the apolipoprotein E gene (ApoE) and certain BuChE variants that predict increased AD risk and poor response to anticholinesterase therapy. We measured BuChE activity and protein level in CSF of eighty mild(More)
The toxicological literature is replete with studies which have attempted to correlate differences in in vivo sensitivity to anticholinesterases with a common in vitro measure: acetylcholinesterase (AChE) IC50 values. Generally, it is assumed that these IC50 values reflect the intrinsic sensitivity of the AChE molecule to the inhibitor. Our goal was to(More)
Butyrylcholinesterase purified from human plasma and acetylcholinesterase purified from human red blood cells were used to immunize separate groups of BALB/c mice. A solid-phase immunoadsorbance assay was developed to screen and characterize antibodies specific for the cholinesterases. Immunized spleen cells were fused with a non-immunoglobulin-secreting(More)
Successive rational mutations of human butyrylcholinesterase (BChE) followed by fusion to human serum albumin have yielded an efficient hydrolase that offers realistic options for therapy of cocaine overdose and abuse. This albumin-BChE prevented seizures in rats given a normally lethal cocaine injection (100 mg/kg, i.p.), lowered brain cocaine levels even(More)
We have mapped areas within the central nervous system (CNS) of the developing fetal rat which immunostain for the 1,25-dihydroxyvitamin D3 receptor (VDR). The VDR was detected from days 12 to 21 of gestation throughout the CNS; immunostaining was particularly intense in the neuroepithelium and within the differentiating fields of various areas of the(More)
Enzyme-linked immunosorbent assays for acetylcholinesterase (AChE) and for butyrylcholinesterase (BuChE) were markedly more specific than conventional assays using selective enzyme inhibitors. The new assays were used with blood and brain samples containing traces of one enzyme dominated by large amounts of the other. The results showed that human plasma(More)
We have studied the retrograde axonal transport of dopamine-beta-hydroxylase (DBH) with the aid of a new stop-flow technique. Rabbit sciatic nerves in vitro were incubated in chambers which exposed different regions to oxygenated physiological saline solution at different temperatures. These chambers contained no mechanical barriers that could generate(More)