Joseph W. Kosh

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We characterized the NADPH-dependent metabolism of 17beta-estradiol (E2) by liver microsomes from 21 male and 12 female human subjects. A large number of radioactive estrogen metabolite peaks were detected following incubations of [3H]E2 with male or female human liver microsomes in the presence of NADPH. The structures of 18 hydroxylated or keto estrogen(More)
Acetylcholine-rich synaptic vesicles were isolated from myenteric plexus-longitudinal muscle strips derived from the guinea pig ileum by the method of Dowe, Kilbinger, and Whittaker [J. Neurochem. 35, 993-1003 (1980)] using either unstimulated preparations or preparations field-stimulated at 1 Hz for 10 min using pulses of 1 ms duration and 10 V . cm-1(More)
1. The metabolism of arecoline (ARE) was examined in homogenates of mouse blood, brain, kidney, and liver tissue. 2. Liver and kidney tissues exhibited the greatest rates of ARE metabolism. 3. The specific carboxylesterase inhibitor TOCP (tri-o-tolyl-phosphate) as well as ISO-OMPA (tetraisopropyl-pyrophosphoramide) completely blocked ARE metabolism in liver(More)
A series of N-aryl-2-[[[5-[(dimethylamino)methyl]-2- furanyl]methyl]thio]ethylamino analogs of the H2-antagonist, ranitidine, was synthesized and the abilities of the compounds to alleviate the cholinergic deficit characteristic of Alzheimer's disease evaluated. The compounds were initially tested for their ability to inhibit human erythrocyte(More)
1. Choline, and the choline analogues monoethylcholine (MEC) and N-aminodeanol (NAD) were examined for prophylactic activity in acute acetylcholinesterase inhibitor toxicity in mice. The rank order of potency of the compounds was MEC greater than NAD greater than choline. 2. Simultaneous administration of MEC (60 mg kg-1) or NAD (200 mg kg-1) with(More)
1 The site (i.e. peripheral or central) of the toxicity produced by hemicholinium-3 in mice was investigated. 2 Hemicholinium-3 was measured fluorometrically and acetylcholine was determined by gas chromatography after intraventricular or intraperitoneal administration of hemicholinium-3. 3 Hemicholinium-3 was not detected in the brain nor were(More)
1. The novel choline analogs selenonium choline (SeCh) and acetylselenonium choline (ASeCh) have been examined for selected biological activities. 2. ASeCh was found to be an alternative substrate for acetylcholine esterase with Km and Vmax values similar to acetylcholine. 3. ASeCh and SeCh inhibited acetylthiocholine hydrolysis by acetylcholinesterase with(More)
Famotidine and selected H2-antagonists were evaluated with respect to toxicity and selected pharmacological activities. When administered intraperitoneally to mice at a dose equivalent to 10 times their respective H2-antagonist ED50 values, no deaths were observed. Similarly, no alteration in brain ACh concentrations or overt pharmacological effects were(More)
Hemicholinium-3 (HC-3) was administered intraperitoneally to mice concurrently with the intraperitoneal administration of physostigmine or neostigmine. HC-3 increased the LD50 values for both physostigmine and neostigmine but did not alter the effect on brain ACh levels produced by these agents. Since HC-3 does not cross the blood brain barrier after(More)