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P J Lewis

Publications and source records attributed to P J Lewis.

At least 19 recordsLinked to original sources
PubMed1991

Vigabatrin.

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Aminocaproates↗
PubMed1991

Neuropathologic findings in patients receiving long-term vigabatrin therapy for chronic intractable epilepsy.

Vigabatrin is a new antiepileptic drug that acts by the irreversible inhibition of gamma-aminobutyric acid (GABA) aminotransferase. During animal safety testing, vigabatrin was found to cause reversible intramyelinic edema in the brains of rodents and dogs but not in primates. In humans, the drug is well tolerated, and extensive clinical, neurophysiologic, neurochemical, and psychometric testing has failed to demonstrate any evidence of neurotoxicity. Neuropathologic examination has now been carried out on 62 patients with refractory epilepsy, who were on vigabatrin therapy either prior to undergoing neurosurgery for their epilepsy or before death. A further ten similar cases have been included in the study from age-matched patients with refractory epilepsy who had not been treated with vigabatrin prior to surgery or death. None of the neuropathologic changes seen in the preclinical animals studies have been observed in the human cases. In no case was there considered to be any evidence of myelin microvacuolation or myelin sheath splitting that could be attributed to vigabatrin treatment. Demyelination has never been observed in either the animal or human material. These findings support the clinical tolerability seen in long-term treatment.

Adolescent↗
PubMed1990

Identification of the replication terminator protein binding sites in the terminus region of the Bacillus subtilis chromosome and stoichiometry of the binding.

DNase I footprinting of the interaction between the replication terminator protein (RTP) of Bacillus subtilis and the inverted repeat region (IRR) at the chromosome terminus, to which it binds to block the clockwise replication fork, showed that two major regions of 41 base pairs (bp) were protected from cleavage. These regions corresponded approximately to the imperfect inverted repeats (IRI and IRII) identified previously. Band retardation analyses of the interaction between RTP and portions of the IRR established that each inverted repeat (IRI or IRII) contained two RTP binding sites. By sedimentation equilibrium in the ultracentrifuge, RTP was found to exist as a dimer of 29 kDa at neutral pH and concentrations above 0.2 g/l. Quantitative studies of the RTP-IRR interaction using [3H]RTP and [32P]IRR showed that the fully saturated complex contained eight RTP monomers per IRR. It is concluded that a dimer of RTP binds to each of the four sites in IRR. The apparent dissociation constant for the interaction was estimated (in the presence of 50% glycerol) to be 1.2 x 10(-11) M (dimer of RTP). Glycerol was found to have a marked effect on the affinity of RTP for the IRR and on the relative amounts of the interaction complexes formed; in the absence of glycerol the dissociation constant was approximately 50-fold higher and there was pronounced co-operative binding of RTP dimers to adjacent sites in each inverted repeat. Examination of the DNA sequence in IRI and IRII identified two 8 bp direct repeats in each. The regions protected from DNase I cleavage in each inverted repeat and the protection afforded by a core sequence spanning just one of the 8 bp direct repeats were consistent with each 8 bp repeat representing a recognition sequence for the RTP dimer. A model describing the binding of RTP to the IRR is presented.

Bacillus subtilis↗
PubMed1989

Intra-individual variation in plasma and erythrocyte cholinesterase activities and the monitoring of uptake of organo-phosphate pesticides.

The measurement of plasma and erythrocyte cholinesterase activities is used to monitor absorption of anti-cholinesterase organo-phosphorus compounds. A fall in an individual's enzyme activity signifies excessive exposure if it is clearly greater than the normal intra-individual variation found in unexposed subjects. The extent of normal variation in enzyme activity as measured is dependent on both the true intra-individual biological variation and the precision of the method used. This report defines normal variation in plasma and erythrocyte cholinesterase activity using the assay developed and used routinely in our laboratory. We have also defined the relation between the precision of the assay used by a laboratory and the sensitivity with which a significant depression in successive enzyme measurements can be detected. This allows occupational physicians, who use cholinesterase measurements to monitor organo-phosphate exposure, to establish percentage depressions from their method precision data that may possibly indicate organo-phosphate uptake between successive enzyme measurements. We have calculated that, with our analytical precision, percentage drops between two successive measurements that are greater than 15 and 7.5 per cent for the plasma and erythrocyte enzymes respectively suggest significant organo-phosphorus absorption in pesticide workers.

Cholinesterase Inhibitors↗
PubMed1989

DNA and protein sequence conservation at the replication terminus in Bacillus subtilis 168 and W23.

Cloned DNA from the replication terminus region of Bacillus subtilis 168 was used to identify and construct a restriction map of the homologous region in B. subtilis W23. With this information, DNA from the terminus region of W23 was cloned and the sequence was determined for a 1,499-base-pair segment spanning the expected terC site. The position of the site was then located more precisely. Use of the cloned DNA from strain W23 as a probe for digests of DNA from exponentially growing cells of the same strain established the presence of the slowly migrating replication termination intermediate (forked DNA). The orientation and dimensions of the forked molecule were consistent with arrest of the clockwise fork at the terC site in W23, as has been shown to occur in strain 168. Thus, despite significant differences between the two strains, the same termination mechanism appears to be used. The DNA sequences spanning the terC site in strains 168 and W23 showed a high level of homology (90.2%) close to the site but very little at a distance of approximately 250 base pairs from the site in one particular direction. The overall sequence comparison emphasised the importance of the open reading frame for a 122-amino-acid protein adjacent to terC. Although there were 22 base differences in the open reading frames between the strains, the amino acid sequence of the encoded protein was completely conserved. It is suggested that the amino acid sequence conservation reflects a role for the protein in the clockwise fork arrest mechanism as proposed earlier (M.T. Smith and R.G. Wake, J. Bacteriol. 170:4083-4090, 1988).

Amino Acid Sequence↗
PubMed1989

A protein involved in termination of chromosome replication in Bacillus subtilis binds specifically to the terC site.

The small basic protein encoded by the open reading frame adjacent to the terC site in the Bacillus subtilis chromosome and previously implicated in termination of the replication process was purified. Band retardation assays established that this protein (now called the replication terminator protein, encoded by the rtp gene) binds specifically to a 209-base-pair fragment of DNA within which terC is located.

Bacillus subtilis↗
PubMed1979

Fetal breathing movements and other tests of fetal wellbeing: a comparative evaluation.

Sixty pregnant women whose fetuses were considered to be at high risk were intensively studied with fetal and placental function tests. Fetal breathing movements were studied with real-time ultrasound and the amount of time spent breathing and the variability of the breath-to-breath interval were measured. A reduction in the amount of time the fetus spent making breathing movements and decreased variability were indicative of fetal compromise. When these results were compared with those of other tests of fetal wellbeing measurement of fetal breathing movements and ultrasound assessment of growth were more sensitive tests of fetal wellbeing than the biochemical measures (urinary oestrogen, human placental lactogen, pregnancy-specific beta-1-glycoprotein, and unconjugated oestriol concentrations) or fetal heart rate. The predictive value was highest with serum unconjugated oestriol but the results of other tests were similar. Study of fetal breathing movements or an ultrasonic assessment of growth may provide a better screening test for fetal compromise than biochemical estimations.

Estriol↗
PubMed1979

Prophylaxis of neonatal jaundice with maternal antipyrine treatment.

A randomised controlled trial of antipyrine (phenazone) in the prophylaxis of neonatal jaundice was completed in 48 women. Treatment of mothers from the 38th week of pregnancy reduced neonatal plasma-bilirubin concentrations on the 4th day after birth by an average of 44%. Prophylaxis of neonatal jaundice merits a wider trial.

Antipyrine↗
PubMed1979

Measurement of 6-oxo-PGF1 alpha in human plasma using gas chromatography-mass spectrometry.

The plasma concentration of the prostacyclin (PGI2) hydration product 6-oxo-PGF1 alpha has been assayed by stable isotope dilution GC-MS in six normal volunteers infused with increasing doses of PGI2 intravenously. The predosing levels of 6-oxo-PGF1 alpha ranged between 114 and 266 pg/ml. Infusion of PGI2 increased 6-oxo-PGF1 alpha concentration in plasma but the increments were lower than expected suggesting less conversion of the PGI2 to 6-oxo-PGF1 alpha at high infusion rates.

6-Ketoprostaglandin F1 alpha↗
PubMed1979

Fetal breathing patterns in intrauterine growth retardation.

Fetal breathing movements were studied with real time ultrasound in 21 normal fetuses and 30 fetuses born small-for-dates (less than the 5th centile). The events of the study period were recorded on punched paper tape which was subjected to computer analysis. In the normal group the percentage time of breathing was 54 +/- 12.7 (mean +/- SD). The breath to breath interval was 1.34 +/- 0.25 seconds and the coefficient of variation of this interval was 49.6 +/- 7.7 per cent. In 17 of the small-for-dates group amount of breathing was reduced with short breathing episodes and long apnoea intervals. In the other 13 patients in the small-for-dates group the coefficient of variation for the breath to breath interval was significantly reduced (39.6 +/- 7.9 per cent, p less than 0.01).

Female↗