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Biomedical subjects

J S Oliver

Publications and source records attributed to J S Oliver.

At least 19 recordsLinked to original sources
PubMed1991

Terpenoid biosynthesis and the stereochemistry of enzyme-catalysed allylic addition-elimination reactions.

Allylic addition-elimination reactions are widely used in the enzyme-catalysed formation of terpenoid metabolites. It has earlier been shown that the isoprenoid chain elongation reaction catalysed by farnesyl pyrophosphate synthase involving successive condensations of dimethylallyl pyrophosphate (DMAPP) and geranyl pyrophosphate (GPP) with isopentenyl pyrophosphate (IPP) corresponds to such an SE' reaction with net syn stereochemistry for the sequential electrophilic addition and proton elimination steps. Studies of the enzymic cyclization of farnesyl pyrophosphate (FPP) to pentalenene have now established the stereochemical course of two additional biological SE' reactions. Incubation of both (9R)- and (9S)-[9-3H,4,8-14]FPP with pentalenene synthase and analysis of the resulting labelled pentalenene has revealed that H-9re of FPP becomes H-8 of pentalenene, while H-9si undergoes net intramolecular transfer to the adjacent carbon, becoming H-1re (H-1 alpha) of pentalenene, as confirmed by subsequent experiments with [10-2H, 11-13C]FPP. These results correspond to net anti-stereochemistry in the intramolecular allylic addition-elimination reaction. The stereochemical course of a second SE' reaction has now been examined by analogous incubations of (4S,8S)-[4,8-3H,4,8-14C]FPP and (4R,8R)-[4,8-3H, 4.8-14C]FPP with pentalenene synthase. Determination of the distribution of label in the derived pentalenenes showed stereospecific loss of the original H-8si proton. Analysis of the plausible conformation of the presumed reaction intermediates revealed that the stereochemical course of the latter reaction cannot properly be described as either syn or anti, since cyclization and subsequent double bond formation require significant internal motions to allow proper overlap of the scissile C-H bond with the developing carbocation.

Carbon Radioisotopes↗
PubMed1989

2-(Fluoromethyl)-3-phytyl-1,4-naphthoquinone and its 2,3-epoxide. Inhibition of vitamin K epoxide reductase.

2-(Fluoromethyl)-3-phytyl-1,4-naphthoquinone (7) was synthesized from the known compound 2-bromo-3-methyl-1,4-dimethoxynaphthalene by N-bromosuccinimide bromination of the 3-methyl group, conversion to the corresponding 3-fluoromethyl compound with silver fluoride, attachment of the 3-phytyl substitutent via the lithium diaryl cuprate and phytyl bromide, and then silver oxide oxidation to 7. Epoxidation with basic hydrogen peroxide gave the corresponding 2,3-oxide (1) in a very low yield. Compound 1 was not a time-dependent inhibitor of beef liver microsomal vitamin K epoxide reductase, but it was a competitive, reversible inhibitor. It was not possible to determine if 1 was a substrate for the enzyme because the expected product of reduction, namely 7, rapidly decomposed under the assay conditions.

Animals↗
PubMed1988

Rapid extraction of oxazepam from greyhound urine for high performance liquid chromatography analysis.

A rapid and efficient procedure is described for the extraction and analysis of oxazepam, the major urinary metabolite of diazepam in greyhounds. Urine was extracted by passing through a bonded silica column (Bond Elut) following enzyme hydrolysis. The adsorbed drug was eluted and then detected and measured by high performance liquid chromatography (HPLC). Recoveries were in excess of 85% at 50 ng/ml concentrations. Detection was possible up to 30 h after a single oral dose of diazepam (5 mg).

Animals↗
PubMed1987

Fatal outcome following inhalation of Tipp-Ex.

Recent measures to combat glue sniffing have led to a decrease in the availability of toluene-based glues. As a result, abuse of other more accessible solvents appears to have increased. Of particular concern are the halogenated hydrocarbons which are more likely to cause fatal cardiac arrhythmias than toluene. We wish to report three cases presenting within a period of six months where death occurred following inhalation of Tipp-Ex, a seemingly innocuous preparation of 1,1,1-trichloroethane which is widely available in offices and schools.

Acute Disease↗
PubMed1986

Sedation in intensive care: morphine and renal function.

Intravenous morphine infusions have been administered to 12 critically-ill patients during controlled ventilation. Acute oliguric renal failure was present in 4 patients, who were treated with a combination of haemofiltration and haemodialysis. Severity of physiological disturbance was assessed using a modified APACHE Score, level of sedation by a linear-analogue scale, and blood morphine levels by high-pressure liquid chromatography. Morphine clearance was impaired in renal failure, and was dependent on haemofiltration volumes; accumulation of morphine did not occur during this form of treatment. Conscious level was clearly more closely related to the degree of physiological disturbance than blood morphine levels; and for a given blood morphine level, depression of consciousness was more pronounced the greater the degree of physiological disturbance. Use of a physiological sickness score may help to clarify some of the factors influencing cerebral function during critical illness. Careful clinical monitoring of level of sedation is important in patients with oliguric renal failure receiving morphine, and haemofiltration appears to reduce the risk of morphine accumulation in these patients.

Acute Kidney Injury↗
PubMed1981

Solvent encephalopathy.

Nineteen children aged 8-14 years were admitted over a six-year period with an acute encephalopathy due to toluene intoxication. Seven had a history of euphoria and hallucinations. The remainder presented with coma (4), ataxia (3), convulsions (3), and behaviour disturbance with diplopia (2), A history of glue sniffing was elicited in 14, but in the remainder toluene assay confirmed the diagnosis. Thirteen children recovered completely; five still had psychological impairment and personality change on discharge from hospital but were lost to follow-up, and one has a persistent cerebellar ataxia one year after the acute episode, despite absence of further exposure. Toluene inhalation is an important cause of encephalopathy in children and may lead to permanent neurological damage. Diagnosis is most important if further damage due to continued abuse is to be prevented, and toluene assay is a valuable aid to diagnosis.

Adhesives↗
PubMed1980

Oral sustained-release aminophylline in medical inpatients: factors related to toxicity and plasma theophylline concentrations.

1 Consecutive medical inpatients expected to benefit from a theophyllinate were treated with sustained-release aminophylline in a protocol conforming with ordinary practice. Of 16 patients, five had toxicity with aminophylline 450 mg daily, and a further three with 900 mg daily. Toxicity was serious in three patients. 2 Toxicity was significantly less common in cigarette smokers, and was related to higher plasma theophylline concentrations. However, there was a large overlap between concentrations associated with toxicity (as low as 9 micrograms/ml) and the accepted therapeutic range (5-20 micrograms/ml). Most patients with toxicity had theophylline levels within the therapeutic range. 3 For the same dose of aminophylline there was sevenfold variation between patients in plasma theophylline, with higher concentrations in non-smokers, infrequent alcohol users, older patients, those with left ventricular failure and those with lower serum transaminases. There variables could not be separated completely because of the small number of observations. 4 A nomogram for aminophylline dosage or monitoring of serum theophylline levels would have prevented little of the toxicity observed in these patients, although these measures would ensure that therapeutic concentrations were attained, and might prevent life-threatening toxicity.

Administration, Oral↗