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Biomedical subjects

P R Lewis

Publications and source records attributed to P R Lewis.

At least 19 recordsLinked to original sources

Effect of myelination on the conduction velocity of optic nerve fibres.

It was proposed by Rushton in 1951, from theoretical considerations, that myelinated fibres less than 1 micron in diameter would conduct more slowly than unmyelinated fibres of the same size and that myelinated fibres below about 0.7 micron would not conduct at all. The experimental data on which he based his theory are all from the peripheral nervous system where small myelinated fibres are rare, and no experimental verification of Rushton's hypothesis has been attempted. In mammalian optic nerve, nearly all the fibres are myelinated; yet half have diameters below 1 micron, with many below 0.7 micron. The many studies of conduction velocities in the visual system enable a test of Rushton's hypothesis to be made. We have examined the correlations between conduction velocity and fibre diameter from a wide range of published studies of the mammalian visual system. The results of our analysis suggest that the small myelinated fibres of the optic nerve and optic tract conduct action potentials more rapidly than is predicted by Rushton's hypothesis, while the unmyelinated axons within the retina actually conduct more slowly than predicted. There is no reason to believe, in this case, that myelination of a small axon will reduce its conduction velocity.

Action Potentials

Contraceptive effects of extended lactational amenorrhoea: beyond the Bellagio Consensus.

We have recorded the duration of lactational anovulation and amenorrhoea in a well-nourished group of Australian women who breastfed their babies throughout the study. The data enabled us to compare the theoretical cumulative probability of conception among breastfeeding women who had unprotected intercourse irrespective of their menstrual status with that of those who had unprotected intercourse only during lactational amenorrhoea. Breastfeeding alone is not an effective form of contraception, since all the women in our study resumed normal ovulation while still breastfeeding. However, among women who have unprotected intercourse only during lactational amenorrhoea but adopt other contraceptive measures when they resume menstruation, only 1.7% would have become pregnant during the first 6 months of amenorrhoea, only 7% after 12 months, and only 13% after 24 months. Thus for our women it would be possible to extend the Bellagio Consensus Conference guidelines which stated that lactational amenorrhoea can only be relied on as a contraceptive for the first 6 months post-partum in women who are fully or almost fully breastfeeding. The lactational amenorrhoea method can be relied on for excellent contraceptive protection in the first 6 months of breastfeeding, irrespective of when supplements are introduced into the baby's diet; for women who continue to breastfeed the method can also give good protection for up to 12 months post partum. Once menstruation has returned, other forms of contraception are essential to prevent pregnancy.

Amenorrhea

The resumption of ovulation and menstruation in a well-nourished population of women breastfeeding for an extended period of time.

We have studied a large group of Australian women breastfeeding for an extended period of time to determine the duration of lactational anovulation (n = 89) and amenorrhea (n = 101). Salivary progesterone assays were used to determine ovulation. These women had a mean of 322 days of anovulation and 289 days amenorrhea. Less than 20% had ovulated and less than 25% had menstruated by 6 months postpartum. The latest ovulation was at 750 days and the latest menstruation at 698 days. There was no significant correlation between any measure of maternal nutritional status and the duration of anovulation or amenorrhea. Neither the time of first supplement introduction to the baby nor the amount of supplement given was an accurate predictor of the return of ovulation or menstruation. However, our results clearly show that lactational amenorrhea can provide good protection against pregnancy in the 1st 6 months postpartum, even in well-nourished women who are giving their babies supplemental feeds.

Adult

Vaccination against lumpy jaw and measurement of antibody response in wallabies (Macropus eugenii).

Successful protection against lumpy jaw disease in a colony of captive wallabies (Macropus eugenii) was induced by vaccination with a commercial ovine footrot vaccine. No mortalities attributable to lumpy jaw were observed in 69 vaccinated animals while six of 42 unvaccinated control wallabies died of the disease. Vaccinated animals exhibited significant increases in antibody titres to Bacteroides nodosus after the first and second doses of vaccine. Titres were measured by an enzyme-linked immunosorbent assay.

Animals

The characterization of the mutagenic activity of soil.

The solvent extracts of non-agricultural soil were shown to cause a potent mutagenic response to Salmonella bacteria. The extract of soil from local sites had activities of 100,000-250,000 TA98 revertants per kg with S9 activation and 44,000-83,000 revertants per kg to TA100 with activation. The soil is mutagenic to both strains without S9, but at lower levels. Nitroreductase-deficient bacterial strains show that the soil extract may have mutagenic compound(s) containing a nitro group. The revertant numbers per gram of soil are lowest at the surface, increase at 4-10 cm and decrease in a linear fashion to a depth of 0.5 meter. HPLC fractionation shows that there is more than one separable component responsible for the mutagenicity of the soil. The source and consequences of the high levels of mutagenicity in 'ordinary soil' are unknown. Soil mutagens can be a significant complicating factor to those using the Ames/Salmonella assay for environmental sampling.

California

Salivary oestriol and progesterone concentrations in women during late pregnancy, parturition and the puerperium.

Oestriol and progesterone concentrations were measured by specific radioimmunoassays in the saliva of six women on a daily basis during the last month of pregnancy, at frequent intervals during labour and daily during the puerperium. Salivary steroid concentrations are thought to reflect the circulating concentrations of the free hormone, and hence may be more biologically relevant than the total plasma concentration, or the urinary excretion of a metabolite. There was no sign of a fall in salivary oestriol or progesterone concentrations before the onset of labour. During the first and second stages, the concentrations fluctuated widely, perhaps due to alterations in uterine blood flow. After delivery of the placenta, hormone concentrations declined abruptly. Oestriol reached undetectable levels of less than 0.1 nmol/l within a day, whereas progesterone concentrations declined somewhat more slowly, approaching follicular-phase values after 2-3 days. This slower decline in the concentration of progesterone may be due to a leaching-out of the hormone from body fat stores. The absence of any prepartum progesterone withdrawal presumably explains the characteristic postpartum delay in the onset of lactogenesis.

Adult

The isolation and identification of a new mutagen from fried ground beef: 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).

A new mutagenic compound has been isolated from ground beef which was fried at 300 degrees C for 5.5 min on each side. The new mutagen was purified using an aqueous acid extraction, XAD-2 adsorption-solvent elution, a series of preparative and analytical h.p.l.c. purification steps, and monitored with the Ames/Salmonella assay. This study reveals a new mutagen member of the amino-imidazoazaarene class of aromatic amines, having a mol. w of 224, and a formula of C13H12N4 as determined by high-resolution mass spectrometry. N.m.r. spectrometry supports the structure, 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), for the new mutagen. The 1-methyl and 3-methyl synthesized isomers of PhIP were compared to the purified mutagen. The two isomers had identical mass spectra to the purified compound, but only the 1-methyl isomer showed similar u.v. and n.m.r. spectra. The two synthetic isomers were separable by h.p.l.c. and the beef derived component co-eluted with the 1-methyl-PhIP isomer. PhIP has a specific activity in the Ames/Salmonella assay of 1950 revertants/microgram. Although it is not as mutagenic as other compounds isolated from fried beef (e.g. MeIQx, 58 000 revertants/microgram) it is the most abundant mutagenic compound by mass in fried beef. PhIP is present at approximately 15 p.p.b. of the original weight of uncooked beef (accounting for 75% of the mass of genotoxic material) and contributes 18% of the total mutagenicity of the fried beef.

Animals

Prostaglandin in the peripheral plasma of tammar wallabies during parturition.

Tammar wallabies (Macropus eugenii) were observed for 7 days, 24 h/day, at the expected time of birth in two consecutive breeding seasons. Blood was collected from the lateral tail vein 1-2 days before birth, then at 10- to 20-min intervals in the peripartum period and less frequently to 30-h post partum. Plasma was assayed for the prostaglandin metabolite 13,14-dihydro-15-oxo-prostaglandin F2 alpha (PGFM), progesterone and LH. An assay for PGFM was validated which allows direct measurement in 100 microliter unextracted plasma with a sensitivity of 0.14 nmol/l (50 pg/ml). There was a short-lived peak of PGFM immediately before or at birth (7.15 +/- 2.52 nmol/l; 2536 +/- 892 pg/ml) which declined to less than 0.28 nmol/l (100 pg/ml) within 2-h post partum. Progesterone concentrations declined about the time of birth, coincident with the peak of PGFM, and reached levels observed in lactationally quiescent animals by 16-h post partum, which was also the time of the LH peak. The transient prostaglandin pulse was detected only by frequent sampling and suggests that, as in other mammals, prostaglandin is important in parturition.

Animals

Effects of temperature, patty thickness and fat content on the production of mutagens in fried ground beef.

The high-pressure liquid chromatography (HPLC) profiles of mutagenic components were compared for extracts of ground beef patties fried at 200, 250 and 300 degrees C for 6 min/side. The HPLC profiles of the mutagenic samples were similar, although total mutagenic activity in Salmonella typhimurium TA1538 was roughly four times as high after the 300 degrees C than after the 200 degrees C frying. Six mutagenic peaks were analysed quantitatively at different temperatures and meat thicknesses. Two major components, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and 2-aminotrimethylimidazo[4,5-f]quinoxaline, and a minor component, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), were all present at the three different temperatures. Thus, in general, cooking temperature seems to have a major effect on the quantities of mutagens produced but not on their HPLC profiles. The thickness of the meat patty did not affect the total yield of mutagens except at longer cooking times (8-10 min/side) and, in general, neither did it affect the HPLC profiles of the mutagenic components. Total mutagenic activity increased with increasing cooking times. Increasing the fat content lowered the total mutagenicity, with 150,000 revertants/kg of fresh beef at 30% fat compared with 230,000 revertants/kg at 15%, but had little effect on the mutagenicity due to IQ.

Animals

Skin diving fatalities in New Zealand.

A review of skin diving fatalities in New Zealand for the period 1961--1973 revealed 28 deaths of which 21 were scuba divers. Two-thirds of the scuba deaths occurred in water less than 15m deep. Running out of air and lack of essential equipment were frequent contributory factors. The pathological findings are presented and show drowning to be the most common mode of death. Some deficiences in the assessment of these fatalities are discussed.

Adolescent

Investigation of a dopaminergic mechanism for regulating oxytocin release.

The isolated hypothalamo-neurohypophysial system (HNS) of male rats was incubated with putative neurotransmitters in vitro to determine their significance in regulating oxytocin release. Dopamine was found to inhibit the spontaneous release of oxytocin from the HNS in a dose-related manner. The maximum inhibition produced by dopamine (10(-9) M) was significantly different from control values and was blocked by haloperidol (5 x 10(-5) M). Apomorphine (10(-9) M) mimicked the effect of dopamine on this system. The type of receptor involved in the inhibitory effect on oxytocin release is unclear, although a dopaminergic mechanism in vivo. When levodopa plus carbidopa were injected into male rats, the gland content of oxytocin in these animals was significantly increased over control values. When a similar dosage regimen was employed with pregnant rats beginning on day 16 of gestation, levodopa plus carbidopa delayed the average delivery time 12 hr. The results of these studies are also consistent with a dopaminergic mechanism for the regulation of oxytocin release.

Animals

Regional distribution of choline acetyltransferase and acetylcholinesterase within the amygdaloid complex and stria terminalis system.

The distribution of "marker" enzymes for cholinergic neurons has been studied in 10 subdivisions of the amygdaloid complex of the rat brain. Choline acetyltransferase activity was measured using a radiochemical method in samples dissected from fresh serial sections. Acetylcholinesterase was studied using a histochemical procedure. Both enzymes had similar patterns of distribution within the amygdaloid complex and were most concentrated in the posterior lateral and basolateral nuclei and in the nucleus of the lateral olfactory tract. These enzymes were much less concentrated in the cortical, medial, central, and basomedial nuclei. Large differences in acetylcholinesterase staining were found within the lateral posterior and the basolateral nuclei and within the pyriform cortex. Biochemical studies showed a parallel distribution of choline acetyltransferase within these nuclei. The results indicate that cholinergic neural elements in the amygdala are concentrated primarily in the basolateral complex and suggest that this region may be innervated by cholinergic fibers traveling in the ventral amygdalo-fugal pathway.

Acetylcholinesterase

Effects of vagotomy on the distribution of cholinesterases in the cat medulla oblongata.

Histochemical study of the distribution of cholinesterases in the cat medulla oblongata reveals that all neurones in the dorsal motor nucleus of the vagus (DMV) contain true cholinesterase (AChE) but, while most contain this enzyme alone, a small proportion of cells contain pseudocholinesterase (BuChE) as well. Cervical vagotomy affects the two types of cell to different degrees of severity. The BuChE-containing neurones lose their enzyme completely within 2-3 weeks and they atrophy and disappear as a result of the operation. On the other hand, the reaction is less severe and is reversible in those cells containing AChE only. Vagotomy also causes reduction of AChE and BuChE staining in the nearby area subpostrema; the depletion here is pronounced at 2-3 weeks and recovery occurs within the year. These findings suggest that some cells in the area subpostrema project peripherally via the vagus and that the area is part of the vagal nuclear complex. Moreover, capilllaries in the area contain AChE and BuChE in the endothelial lining and this is one of the few areas of the cat hindbrain to exhibit such vascular enzyme activity. The ependyma of the area postrema, which overlies the area subpostrema, is heavily stained for BuChE but this is unaffected by vagotomy.

Animals

Cholinesterase activity in the hypoglossal nucleus of the rat and the changes produced by axotomy: a light and electron microscopic study.

Within the hypoglossal nucleus large amounts of acetylcholinesterase (AChE) activity are present in all the neurons, whereas intracellular butyrylcholinesterase (BuChE) activity occurs only within a ventro-caudally situated cluster of cells. AChE activity within the neurons occurs mainly in the cisternae of the granular endoplasmic reticulum but there is some in the intermembranous space of the nuclear envelope and in the Golgi complexes. In the neuropil, reaction product is seen along some axonal and synaptic membranes. The distribution of BuChE in the ventro-caudal cells is identical with that of AChE except that BuChE activity is absent from the neuropil. The level of intraneuronal AChE activity falls rapidly during the first few days after axotomy. The fall is due partly to a dissolution and peripheral migration of the E.R. but also to a decrease in AChE content of the E.R. that remains. Return of staining begins in the 4th week and continues as the E.R. reassembles. Staining in the neuropil falls more slowly, but recovers less completely. The ventro-caudal group of cells shows the same kinds of change, but more dramatically. BuChE activity returns only erratically and never completely. The similarity in normal distribution, and in response to axotomy, of the two cholinesterases suggests that their functions are related.

Acetylcholinesterase

The localization of acetylcholinesterase in the locus coeruleus of the normal rat and after 6-hydroxydopamine treatment.

The locus coerulus is a densely packed group of neurons in the floor of the fourth ventricle, and is the largest aggregate of noradrenaline-containing cells in the mammalian brain. The distribution within the locus of acetylcholinesterase (AChE), which is present in high concentration, has been studied at light and electron microscope level, both in normal rats and in ones treated with 6-hydroxydopamine. Neuronal enzyme activity is entirely intracellular and mainly concentrated in stacks of ER which occupy much of the cell cytoplasm. There are no indications of a cholinergic input. After 6-hydroxydopamine treatment extensive cell death occurs and AChE activity virtually disappears. A majority of the many blood vessels in the locus also stain strongly for AChE, unlike those present in most other areas of the rat brain. The locus coeruleus therefore represents an area of the rat brain with a high content of AChE, but no evidence of a cholinergic mechanism. Some possible explanations for this anomalous presence of AChE are briefly discussed.

Acetylcholinesterase