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Biomedical subjects

A Roberts

Publications and source records attributed to A Roberts.

At least 289 records · Page 16Linked to original sources

The efficacy of a serum screening service for neural-tube defects: the South Wales experience.

Serum-alpha-fetoprotein (AFP) levels were measured in more than 15 000 pregnant women in an investigation designed to examine the operational issues entailed in a large-scale population screening programme for antenatal detection of neural-tube defects. The proportion of open neural-tube defects (ONTD) terminated as a result of serum screening was 56.1% (66.6% for anencephaly and 40.7% for open spina bifida). The principle causes of poor efficacy were: failure of pregnant women to undergo screening (18.2% of ONTD were not screened); failure of the screening test to detect ONTD (20.4% of those screened were below the 90th centile); decisions against termination of detected ONTD (14% of ONTD detected by serum AFP were not terminated). Given present practices and knowledge it is doubtful whether overall efficacy levels above 65% for open spina bifida can be achieved under normal service conditions. The establishment of a regional or national screening programme on grounds of clinical efficacy alone may be premature. The decision would seem to hinge principally around a careful consideration of the economic issues.

Anencephaly↗

Competition during innervation of embryonic amphibian head skin.

We have examined the initial innervation of the head skin in Xenopus laevis embryos which is by two classes of trigeminal mechanoreceptor with beaded 'free' nerve-endings. By recording receptive areas electrophysiologically and staining peripheral sensory neurites with horseradish peroxidase, we have shown that 'movement detector' neurites from one trigeminal ganglion do not normally cross the dorsal midline of the head to innervate areas of skin on the opposite side. However, if one trigeminal ganglion is removed before peripheral innervation starts, movement detector neurites from the intact side will now cross the midline to innervate contralateral skin. These observations suggest a specific competitive interaction between movement detector neurites during their innervation of head skin. The second class of receptor, 'rapid transient' detectors, have a different pattern of innervation, crossing the midline in both normal and operated animals.

Animals↗

The anatomy of two functional types of mechanoreceptive 'free' nerve-ending in the head skin of Xenopus embryos.

The structure of the two functional types of 'free' nerve-ending in the head skin of late Xenopus embryos has been examined by horseradish peroxidase staining through their cells in the trigeminal ganglion and by electron microscopy. Type I neurites are identified as the 'movement' detectors by their purely homolateral innervation. They have many fine branches between the superficial skin cells, bearing numerous large varicosities. Type II neurites cross the midline to innervate both sides of the head as do the 'rapid transient' detectors found by physiology. They have a few fairly straight branches between the skin cell layers with few elongated varicosities.

Animals↗

Induction of expression of the rat G5 nervous system antigen occurs postnatally.

G5 is a cell membrane component found in high levels in the adult rat central nervous system and in low levels on some cells of the rat immune system. Binding assays with adult brain particulate protein preparations and monoclonal antibody to G5 (G5-IgG) gave highest activity in cerebral cortex and lowest in the white matter rich regions pons and spinal cord. Three peripheral nervous system components had no G5 activity. Analysis of G5 content in particulate protein preparations from whole rat brain of ages embryonic day 15 to adult indicates that G5 is present in negligible amounts in the newborn rat. It increases in both specific and total activity to reach adult levels by postnatal day 30. A similar induction curve was observed with cerebellum samples. In adult cerebellum, high levels of G5 were found in the molecular layer using both autoradiographic and immunofluorescence techniques. White matter had essentially no activity. The density and uniformity of reaction product in these techniques suggest that G5 is present on a major cellular constituent of the molecular layer. Pharmacologic experiments indicate G5 is not detectable on climbing fibers or adrenergic fibers. Cerebellar samples from juvenile rats also had predominant G5 activity in the forming molecular layer.

Animals↗

Comparative effects of nitroglycerin and nitroprusside on prostacyclin generation in adult human vessel wall.

The precise mechanism of vasodilatory actions of nitroso-compounds is not clear. It has been suggested that these drugs might modulate release of the vasodilator, prostacyclin, from cultured endothelial cells and bovine arteries or potentiate actions of prostacyclin. This study was designed to examine the effects of nitroglycerin and nitroprusside on prostacyclin release from adult human vasculature. Saphenous vein ring preparations were incubated with nitroglycerin or nitroprusside and arachidonic acid, the substrate for prostacyclin. Vascular rings incubated with nitroglycerin released significantly more prostacyclin (measured as 6-keto-prostaglandin F1 alpha, a stable hydrolysis product of prostacyclin by radioimmunoassay) compared with the control vascular rings (p less than 0.02). This increase was observed at the therapeutic concentrations of nitroglycerin (5 to 10 ng/ml). However, incubation of saphenous vein rings with nitroprusside in concentrations as high as 1 microgram/ml was not associated with any increase in prostacyclin release. Prior incubation of vascular rings with the cyclooxygenase blocker, indomethacin, inhibited nitroglycerin-induced prostacyclin release. Incubation of vascular rings with the selective thromboxane A2 blocker, OKY 1581, resulted in additional prostacyclin release with nitroglycerin treatment, presumably by inhibiting vessel wall-generated thromboxane A2. Nitroprusside had no significant effect on prostacyclin release from indomethacin-treated or OKY 1581-treated vascular rings. This study suggests significant stimulatory effects of nitroglycerin, but not of nitroprusside, on prostacyclin release from human saphenous vein. Nitroglycerin-induced prostacyclin release may be an important mechanism of its antiischemic actions in human subjects.

6-Ketoprostaglandin F1 alpha↗

Hemolysin production as a virulence marker in symptomatic and asymptomatic urinary tract infections caused by Escherichia coli.

Potential virulence, as defined by combined levels of adhesion to urinary epithelial cells, serum resistance, and mouse toxicity, was assessed for Escherichia coli strains causing symptomatic and asymptomatic urinary tract infections in relation to the carriage of hemolysin and other suspected virulence determinants. Hemolysin production (Hly), associated with certain O (O4, O6, O18, and O75), K (5), and hemagglutination (VI and VII) antigenic types but not colicin V production (Cva), was evident in 83 and 60% of isolates in groups possessing high potential virulence and in only 11 and 6% of those with low virulence. Strains of particular O-types were not more virulent per se, but among the serotypes, specific combinations of virulence factors appeared decisive, e.g., O18 HAVI B/D/G Hly(+) K5(+/-) and O18 HAIII/IVB/V Hly(-) Cva(+/-) K1(+/-) strains were, respectively, of high and low potential virulence. Isolates with high potential virulence were found to a similar extent in symptomatic and asymptomatic infections.

Colicins↗

Human vascular tissues produce thromboxane as well as prostacyclin.

Four different types of human blood vessels were examined for spontaneous and arachidonate-stimulated release of prostacyclin (PGI2) and thromboxane A2 (TXA2). Spontaneous PGI2 release was umbilical veins greater than umbilical arteries greater than saphenous veins greater than internal mammary arteries. With stimulation, PGI2 release by all four different vessels increased significantly (P less than 0.001) and was similar. Spontaneous release of TXA2 was also identified from all vessels examined and was similar. With stimulation, TXA2 release from all vessels increased significantly (P less than 0.001). Internal mammary artery released more TXA2 than other vessels on stimulation. The identity of TXA2 was confirmed by similar displacement of TXB2 antibody by TXB2 standards and by multiple dilutions of supernates. Treatment of vessels with aspirin inhibited PGI2 as well as TXA2 release, whereas treatment with OKY 1581 (TXA2 synthetase inhibitor) inhibited TXA2 release only. Two-dimensional thin-layer chromatography showed [14C]arachidonate conversion to PGI2 and TXA2 similar to that measured by radioimmunoassay. These data suggest that TXA2 is synthesized by human vessels. In older vessels when PGI2 generation is decreased, TXA2 production may by of pathophysiological significance.

Adult↗

A study of the growth cones of developing embryonic sensory neurites.

The scanning electron microscope was used to examine the growth cones of sensory neurites on the basal lamina of the trunk skin and on the myotomes in dissected embryos of the amphibian, Xenopus laevis. On the myotomes growth cones are large and flat with extensive lamellipodia and many filopodia. On the skin growth cones are smaller and have simpler processes particularly in more ventral positions. Where growth cones contact each other or other neurites they are very intimately apposed and show many indications of strong mutual adhesion. Fasciculation and separation of growing neurites is described and the conditions leading to fasciculation are considered. Measurements of growth cones on the myotomes and different dorsoventral regions of the skin are interpreted in terms of possible differences in the adhesiveness of these substrates. We conclude that many of our observations can be explained by differences in substrate adhesion to the growth cones but that the skin may have some special, unknown attraction for them.

Animals↗

The early development of the primary sensory neurones in an amphibian embryo: a scanning electron microscope study.

We have described the development of the primary sensory system of the trunk region of Xenopus laevis embryos from larval stages 21 to 32. The system is based upon Rohon-Beard and extramedullary cells, which have central axons forming a dorsolateral spinal tract and peripheral neurites which innervate the skin. The pioneer axons of the central tract grow along the outer surface of the cord at stage 22. These pioneer axons may be used by secondary axons as a growth substrate. As the tract forms it is covered by the radially expanding distal processes, 'end feet', of the ependymal cells of the cord. Cell bodies of the extramedullary cells bulge out of the cord surface, and are first seen between the newly segmented myotomes, at stage 24. Peripheral neurites from these extramedullary cells grow out laterally from the cord. The Rohon-Beard cells, located within the cord, produce similar peripheral neurites which grow laterally with the extramedullary cell neurites, using them as a substrate. The neurites form bundles which coincide with the intermyotomes and are periodically spaced. The growth cones of these neurites contact the outer surface of the myotomes and proceed ventrally, first on the myotomes and then on the basal lamina of the skin. 'Pioneer' neurites are used by later neurites as a growth substrate, but not to the exclusion of all other substrates. The neurites form a plexus on the skin's basal lamina and contact the underlying epidermal cells through holes in the basal lamina. These holes occur in positions over the intercellular boundaries of the epidermal cells.

Animals↗

Screening for neural-tube defects and maternal anxiety.

Anxiety levels were studied in 176 women with raised serum alpha-fetoprotein levels at 16-18 weeks gestation, at the time they attended a central assessment clinic, and again 2-3 weeks later in those not found to have a fetus with a neural-tube defect. Methods of imparting information about the serum screening tests and the manner in which a normal amniotic fluid result was conveyed to the patient were also studied. Overall, women attending the clinic for further assessment were extremely anxious, irrespective of the source of their information. Anxiety scores 2-3 weeks after testing were greatly influenced by whether the patient had been given a definite normal result or whether she was told to assume that the result was normal if she did not hear from the clinic. Patients who, after reassessment, did not require amniocentesis had some residual anxiety in spite of verbal reassurance.

Amniocentesis↗

Segmental giant: evidence for a driver neuron interposed between command and motor neurons in the crayfish escape system.

1. The giant command neurons for tailflip escape behavior in crayfish have been thought to excite the nongiant fast flexor (tailflip producing) motor neurons (FFs) via monosynaptic connections. We show here that excitation of FFs instead occurs via a bilateral pair of segmental giant neurons (SGs) interposed between the command axons and FFs in each segment. 2. Anatomically, the SGs appear to make numerous contacts with ipsilateral command axons and FFs and fewer contacts contralaterally. In contrast, the command axons have only sparse direct connections to the FFs. An SG has an axon in the ipsilateral first ganglionic root and may be a modified swimmeret motor neuron. 3. Each SG is depolarized well beyond threshold by the firing of an ipsilateral command axon and is depolarized to near threshold by the firing of a contralateral command axon. The synapses between command axons and SGs are electrical and probably rectifying. 4. Each FF is excited to a level near firing threshold by the SG ipsilateral to its axon and is excited weakly by the contralateral SG. The synapses between SGs and FFs are electrical and nonrectifying. 5. Variations in excitatory postsynaptic potentials (EPSPs) recorded in FFs during prolonged, high-frequency firing of the command axons can be accounted for by refractoriness of SG spikes, as opposed to refractoriness of dendritic branch spikes as had previously been delivered. 6. These findings illustrate the limitations of conventional tests for monosynapticity. 7. The functional significance of having driver neurons interposed between command neurons and motor neurons is discussed.

Animals↗

Activity of myotomal motoneurons during fictive swimming in frog embryos.

1. Dye-filled microelectrodes have been used to identify and to examine the electrical activity of spinal cord motoneurons during fictive swimming in amphibian embryos. 2. Impaled neurons all had ventral cell bodies, dorsal, lateral, or ventral dendrites, and most showed either damaged or complete peripheral axons projecting out to the myotomes. It was rarely possible to identify cells by recording 1:1 motor root spikes evoked by intracellular current pulses. 3. During fictive swimming, motoneurons are tonically depolarized, fire 1 spike per swimming cycle, and are inhibited in phase with motor root activity on the opposite side. Motoneurons can also fire synchronously on the two sides, at double the normal swimming frequency. They occasionally also show a pattern of lower frequency alternating activity in which there is a prolonged burst of discharge on each cycle.

Animals↗

Tonic and phasic synaptic input to spinal cord motoneurons during fictive locomotion in frog embryos.

1. In curarized, late developmental stage Xenopus embryos, episodes of rhythmic motor root discharge, termed fictive swimming (17), may be evoked by touch or by dimming the lights, as in unparalyzed animals. Motoneurons are tonically depolarized throughout each episode, are phasically excited to fire 1 spike per cycle, and receive a midcycle inhibitory postsynaptic potential (IPSP) in phase with motor root activity on the opposite side. 2. Rostral hemisection of the spinal cord abolishes motor root discharge on the operated side caudal to the cut but leaves activity on the intact side unaffected. In motoneurons, the tonic depolarization is abolished on the hemisected side but is still present on the intact side. This is evidence that the tonic depolarization is a descending drive. 3. Midcycle IPSPs normally seen in motoneurons during fictive swimming are abolished by rostral hemisection of the opposite side of the cord but are still recorded on the cut side. The simplest conclusion is that the inhibitory interneurons responsible lie on the opposite side of the spinal cord to the motoneurons they inhibit, and so represent a reciprocal inhibitory pathway. 4. The phasic excitatory postsynaptic potentials (EPSPs), which drive motoneuron spikes during swimming, are still present on the intact side of a rostrally hemisected cord but are abolished on the operated side. We conclude that the excitatory interneurons responsible lie on the same side of the cord as the motoneurons they excite.

Animals↗

The neuromuscular basis of swimming movements in embryos of the amphibian Xenopus laevis.

When removed from their egg membranes, Xenopus embryos can swim. High-speed cinematography shows that, in swimming, lateral undulations pass rostro-caudally down the body. The swimming rhythm period is 40-100 ms. In swimming, electrical activity in myotomal muscles alternates on opposite sides of a segment and sweeps rostro-caudally in ipsilateral myotomes. Myotome muscle physiology was examined. Muscle fibres are electrically coupled to each other, and the fibres are able to spike. The possible role of a myotomal conduction pathway in swimming is discussed.

Animals↗

The central nervous origin of the swimming motor pattern in embryos of Xenopus laevis.

Rhythmic motor nerve activity was recorded in stage 37/38 Xenopus embryos paralysed with curare. The activity was similar to the swimming motor pattern in the following ways: cycle period (40-125 ms), alternation of activity on either side of a segment, rostro-caudal phase lag. Episodes of rhythmic motor activity could be evoked by stimuli that evoke swimming and inhibited by stimuli that normally inhibit swimming. On this basis we conclude that the swimming motor pattern is generated by a central nervous mechanism and is not dependent on sensory feedback. In addition to the swimming pattern, another pattern of motor activity ('synchrony') was sometimes recorded in curarized embryos. In this, the rhythmic bursts on either side of a segment occurred in synchrony, and the rhythm period (20-50 ms) was half that in swimming. This was probably not an artifact of curarization as there were indications of a similar pattern in uncurarized embryos. Its function remains unclear.

Animals↗

The neuromuscular basis of rhythmic struggling movements in embryos of Xenopus laevis.

Xenopus embryos struggle when restrained. Struggling involves rhythmic movements of large amplitude, in which waves of bending propagate from the tail to the head. Underlying this, electrical activity in myotomal muscles occurs in rhythmic bursts that alternate on either side of a segment. Bursts in ipsilateral segments occur in a caudo-rostral sequence. Curarized embryos can generate motor nerve activity in a struggling pattern in the absence of rhythmic sensory stimulation; the pattern is therefore produced by a central pattern generator.

Animals↗