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Biomedical subjects

M K Johnson

Publications and source records attributed to M K Johnson.

At least 235 records · Page 13Linked to original sources
PubMed1980

Repeated small doses of a neurotoxic organophosphate. Monitoring of neurotoxic esterase in brain and spinal cord.

The effects of small repeated oral doses of mono-2-cresyl diphenyl phosphate (MOCP, 2.5 mg/kg/day) on hen brain and spinal cord neurotoxic esterase (NTE) were measured. The enzyme levels were depressed to about 40% and 55% of normal respectively and maintained at that level for 8 weeks. No clinical and only doubtful histological signs of neuropathy were detected. Neuropathy could be precipitated by depressing the level to < 20% either with a single high dose (50 mg/kg), or by an increase of the repeated dose level to 5 mg/kg/day. There was no correlation between inhibition of NTE in the nervous tissue and the "NTE-like" activity in lymphocytes. "NTE-like" activity in spleen was consistently inhibited but to a lesser extent than that in the brain or spinal cord. Brain AChE and BuChE were not affected.

Acetylcholinesterase↗
PubMed1980

The effects of phenylmethanesulfonyl fluoride on delayed organophosphorus neuropathy.

A delayed localized neuropathy of peripheral nerves in a single hind leg of the cat develops after a single intraarterial 2 mg/kg injection of diisopropylfluorophosphate (DFP). This neuropathy is manifested by a maximum loss of the capacity of soleus alpha-motor nerve terminals to generate stimulus-bound repetition 21 days after DFP exposure. Phenylmethanesulfonyl fluoride (PMSF) is a protective inhibitor of the neurotoxic esterase which is associated with the development of the delayed organophosphorus neuropathy. Pretreatment of cats with PMSF (30 mg/kg i.p.) 24 h before the DFP injection protected the cats from the delayed neuropathy. No clinical neurotoxic signs were observed at 21 days after DFP. The stimulus-bound repetitive capacity of soleus alpha-motor nerve terminals was not lost at this time and its incidence was much greater than that which occurred in cats not pretreated with PMSF.

Action Potentials↗
PubMed1980

Biochemical events in delayed neurotoxicity: is aging of chymotrypsin inhibited by saligenin cyclic phosphates a model for aging of neurotoxic esterase?

Chymotrypsin and neurotoxic esterase (NTE) have some similarities. After inhibition of concentrated (80-800 micro M) chymotrypsin by aryl saligenin cyclic phosphates it is known that aging occurs and some phenolic material becomes attached to protein. This binding has now been shown to be a manifestation of non-specific reaction with any available electrophile such as Tris, reduced glutathione (GSH), or protein. The reaction is therefore not a model for the 100% efficient transfer of alkyl groups to protein which occurs during aging of NTE inhibited by dialkyl phosphates.

Benzyl Alcohols↗
PubMed1980

Delayed neurotoxicity caused by chronic feeding of organophosphates requires a high-point of inhibition of neurotoxic esterase.

Experiments are reported showing that chronic feeding of either mono-2-cresyl diphenyl phosphate or diisopropyl phosphorofluoridate (DFP) to hens does not cause clinically observable delayed neurotic effects prior to a point when inhibition of neurotoxic esterase (NTE) of brain and spinal cord reaches 70-90%. These results are contrary to another study with diisopropyl phosphorofluoridate, which claims neuropathy without high inhibition, but are supported by results of chronic feeding experiments with tri-o-cresyl phosphate. The discrepancy cannot be attributed to differences in the strains of hens used.

Animals↗
PubMed1980

The mechanism of delayed neuropathy caused by some organophosphorus esters: using the understanding to improve safety.

The mechanism of delayed neurotoxicity of some OP (organophosphorus) esters such as DFP (di-isopropyl phosphorofluoridate) and TOCP (tri-o-cresyl phosphate) involves an initial two-step process affecting an esterase called NTE (neurotoxic esterase). This understanding permits the assessment of delayed neuropathic potential in terms of a quantitative measurement of inhibition of NTE in tissue taken from dosed hens. Structure/activity relationships have been rationalized and the neurotoxic potential of those OP esters which are direct inhibitors of esterases may now be assessed in vitro. The response of human NTE can usefully be compared with that of hen NTE. Nil delayed neurotoxic potential is associated with carbamate or phosphinate anticholinesterases which may be designed as insecticides.

Animals↗
PubMed1980

Binding of cholesterol by sulfhydryl-activated cytolysins.

The binding of cholesterol by pneumolysin, alveolysin, and streptolysin O has been demonstrated. The properties of the cytolysin-cholesterol interaction parallel those of cytolysin-erythrocyte interaction in that the reaction is rapid, temperature independent, decreased at elevated pH, and shows the same specificity with respect to other related sterols. However, oxidized or p-hydroxymercuribenzoate-treated thoxin showed no decrease in cholesterol-binding activity, whereas the ability of cytolysin to bind to erythrocytes was modified by such treatment.

Cholesterol↗
PubMed1980

Production and properties of heat-stable extracellular hemolysin from Pseudomonas aeruginosa.

Of 12 strains of Pseudomonas aeruginosa, 10 were found to produce heat-stable extracellular hemolysin in highly aerated peptone broth supplemented with glycerol, fructose, or mannitol. Glucose supported good hemolysin production only in medium that was highly buffered. The yield of both cells and hemolysin was lower with organic acids as supplement. Growth-limiting phosphate concentrations produced maximum hemolysin levels. Purified hemolysin preparations contained two hemolytic glycolipids. The kinetics of hemolysis at various levels of purified lysin and the effects of variation in lysin and erythrocyte concentration are described.

Glycerol↗
PubMed1980

Audit mechanism for hospital drug distribution.

The development and application of a pharmacy department audit of its unit dose drug distribution system is described. Criteria used in the program were based on broad drug distribution criteria developed by the Minnesota Society of Hospital Pharmacists' PSRO Liaison Committee, with subcriteria developed by the staff of the hospital pharmacy department. Month-long audits are based on one of three criteria. A committee consisting of two staff pharmacists, one administrative pharmacist and one technician audits a predetermined number of randomly selected medication orders, medication profiles, filled medication orders or medication drawers. Deficiency patterns are identified, and appropriate corrective action is taken. Audits require approximately eight hours of pharmacist time and three hours of technician time per month per criterion. Audit of the drug distribution system makes pharmacy staff more aware of the quality of service it provides.

Hospital Bed Capacity, 500 and over↗
PubMed1980

Irreversible phosphorylation of brain neurotoxic esterase. The primary event leading to the delayed neuropathy caused by some organophosphorus esters.

Organophosphorus compounds which cause delayed neurotoxic effects phosphorylate a characteristic nervous-tissue protein and inhibit its activity as an esterase. Studies with a variety of inhibitors reveal that the toxic effect does not occur because of the loss of esterase activity but depends on the chemistry of the inhibited enzyme. A process analogous to the 'aging' of inhibited cholinesterase occurs after neurotoxic esterase has been inhibited by neurotoxic agents which leaves a charged acidic group attached to the membrane-bound esterase. This charge could disrupt normal metabolism in the neurone. Protective compounds inhibit neurotoxic esterase but the 'aging' process cannot occur, so that there is no formation of a charged group. Neurotoxic esterase occurs widely in the brain. Attempts are being made to locate the enzyme intraneuronally. The present understanding is of great value in toxicology. However, it has not yet clarified the physiological processes which maintain long axons in normal health.

Animals↗
PubMed1980

Alcohol and elaborative schemas for sentences.

Three experiments were conducted to determine whether alcohol-induced impairments of memory would be reduced by providing subjects with elaborative schemas. Anomalous sentences were presented to sober or intoxicated subjects either alone or with context words to facilitate comprehension. Memory was tested immediately with a yes-no recognition task. The results consistently showed that context words did not increase the number of hits in either sober or intoxicated subjects, and sober subjects made reliably more hits whether or not context words had been provided. The accuracy of recognition of distractors, however, was consistently improved by the presentation of context words, and was much more improved for intoxicated than for sober subjects. The results indicate that alcohol intoxication disrupted the production of elaborative schemas for understanding, but that intoxicated subjects were quite successful at utilizing such schemas as long as the schemas had been provided for them.

Adult↗
PubMed1979

Rapid aging of neurotoxic esterase after inhibition by di-isopropyl phosphorofluoridate.

1. It was proposed [Johnson (1974) J. Neurochem.23, 785-789] that an essential step in the genesis of delayed neuropathy caused by some organophosphorus esters was aging of phosphorylated neurotoxic esterase, involving generation of a charged monosubstituted phosphoric acid residue on the protein. 2. Neurotoxic esterase of hen brain was inhibited with di-isopropyl phosphorofluoridate either unlabelled or mixed-labelled with (3)H and (32)P. 3. Reactivation of inhibited enzyme by KF was possible only immediately after a brief inhibition:aging at pH8.0 and 37 degrees C occurred with a half-life of about 2-4min. 4. When the radiolabelled enzyme was studied no loss of label was observed during the expected aging period, but a change in the nature of the bound radioisotopes occurred (half-life=3.25min). 5. Alkaline hydrolysis of labelled enzyme liberated di-isopropyl phosphate at early times after labelling, but increasing amounts of monoisopropyl phosphate plus a volatile tritiated compound (possibly propan-2-ol) at later times. 6. Treatment of labelled enzyme with KF released di-isopropyl phosphate and caused reactivation of enzyme to similar degrees. It is concluded that the chemical change from di-isopropyl phosphoryl-enzyme to mono-isopropyl phosphoryl-enzyme and the loss of reactivatibility are related. 7. The rate of aging is similar at pH5.2, 6.5 and 8. Aging is unaffected by addition of reduced glutathione and imidazole at pH5.2 or 8, and none of the transferred (3)H is trapped by these reagents. The mechanism of aging must be different from the better-known dealkylation aging of the cholinesterases.

Animals↗
PubMed1979

Some magnetic properties of Pseudomonas cytochrome oxidase.

The magnetic properties of the haem groups of Pseudomonas cytochrome oxidase and its cyanide-bound derivatives were studied in both the oxidized and reduced states by means of m.c.d. (magnetic circular dichroism) at low temperatures. In addition, the oxidized forms of the enzyme were also investigated by e.p.r. (electron-paramagnetic-resonance) spectroscopy, and a parallel study, using both e.p.r. and m.c.d., was made on Pseudomonas cytochrome c-551 to aid spectral assignments. For ascorbate-reduced Pseudomonas cytochrome oxidase, the temperature-independence of those features in the m.c.d. spectrum corresponding to the haem c, and the temperature-dependence of those signals corresponding to the haem d1, showed the former to be low-spin and the latter to be high-spin (s = 2). However, addition of cyanide to the reduced enzyme gave a form of the protein that was completely low-spin. The e.p.r. and m.c.d. sectra of oxidized Pseudomonas cytochrome oxidase and its cyanide derivative were consistent with the haem c and d1 components being low-spin in both cases. Pseudomonas cytochrome c-551 was found to be low-spin in both its oxidized and reduced redox states.

Ascorbic Acid↗
PubMed1979

Fact and fantasy: the roles of accuracy and variability in confusing imaginations with perceptual experiences.

In Experiment 1, pictures were presented to subjects two, five, or eight times, and subjects were asked to imagine each pciture two, five, or eight times. Subsequently, subjects estimated the number of times each picture had been presented. Their estimates of the frequency of these external events were influenced by imagination trials; this effect was greater for good imagers than for poor imagers. Experiment 2 involved a similar design in which subjects were asked either to imagine the same referent for a word or to imagine a different referent for a word on successive imagination trials. Consistency (same referent) did not increase the influence of imaginations on immediate judgments of external frequency. Thus, the results of Experiment 1 were attributed to the greater accuracy (as opposed to greater consistency) of good imagers' internal generations of the stimuli. Furthermore, variation (imagining different referents), like greater accuracy, increased the effects of imagination trials on immediate but not on delayed judgments of frequency. Possible mechanisms underlying these effects are discussed. In general, the two studies show that qualitative characteristics of completely covert generations influence their impact on estimates of the frequency of external events.

Form Perception↗