Measurement of the energy spectrum of cosmic-ray induced neutrons aboard an ER-2 high-altitude airplane.

Crews working on present-day jet aircraft are a large occupationally exposed group with a relatively high average effective dose from galactic cosmic radiation. Crews of future high-speed commercial aircraft flying at higher altitudes would be even more exposed. To help reduce the significant uncertainties in calculations of such exposures, the atmospheric ionizing radiation (AIR) project, an international collaboration of 15 laboratories, made simultaneous radiation measurements with 14 instruments on five flights of a NASA ER-2 high-altitude aircraft. The primary AIR instrument was a highly sensitive extended-energy multisphere neutron spectrometer with lead and steel shells placed within the moderators of two of its 14 detectors to enhance response at high energies. Detector responses were calculated for neutrons and charged hadrons at energies up to 100 GeV using MCNPX. Neutron spectra were unfolded from the measured count rates using the new MAXED code. We have measured the cosmic-ray neutron spectrum (thermal to >10 GeV), total neutron fluence rate, and neutron effective dose and dose equivalent rates and their dependence on altitude and geomagnetic cutoff. The measured cosmic-ray neutron spectra have almost no thermal neutrons, a large "evaporation" peak near 1 MeV and a second broad peak near 100 MeV which contributes about 69% of the neutron effective dose. At high altitude, geomagnetic latitude has very little effect on the shape of the spectrum, but it is the dominant variable affecting neutron fluence rate, which was eight times higher at the northernmost measurement location than it was at the southernmost. The shape of the spectrum varied only slightly with altitude from 21 km down to 12 km (56-201 g cm-2 atmospheric depth), but was significantly different on the ground. In all cases, ambient dose equivalent was greater than effective dose for cosmic-ray neutrons.

Presynaptic localisation of the nicotinic acetylcholine receptor beta2 subunit immunoreactivity in rat nigrostriatal dopaminergic neurones.

Nicotinic acetylcholine receptors (nAChR) are widely distributed in the central nervous system, where they exert a modulatory influence on synaptic transmission. For the striatum, pharmacological evidence supports the presence of presynaptic alpha3beta2* and alpha4beta2* nAChR that modulate dopamine release from nigrostriatal terminals. The objective of this study was to examine the precise subcellular distribution of the nAChR beta2 subunit in these neurones and its localisation at presynaptic sites. Double immunolabelling with tyrosine hydroxylase (TH) at the confocal level revealed that the cell bodies and axon terminals (synaptosomes) of nigrostriatal neurones were also immunoreactive for the nAChR beta2 subunit. Double-preembedding electron microscopy confirmed that beta2-immunogold labelling was enriched in TH-positive terminals in the dorsal striatum. Quantitative analysis of doubly immunogold-labelled sections in postembedding electron microscopy showed that 86% of TH-positive axonal boutons are also labelled for the nAChR beta2 subunit, whereas 45% of beta2 subunit-immunolabeled boutons do not contain TH. Thus the beta2 subunit is localised within at least two populations of axon terminals in the dorsal striatum. In these structures, 15% of beta2 subunit immunoreactivity was at the plasma membrane but was rarely associated with synapses. These findings are compatible with functional presynaptic beta2-containing nAChR that may be stimulated physiologically by acetylcholine that diffuses from synaptic or nonsynaptic sites of acetylcholine release. These results demonstrate the presynaptic localisation of an nAChR subunit in nigrostriatal dopaminergic neurones, providing morphological evidence for the presynaptic nicotinic modulation of dopamine release.

Sensory afferents and motor neurons as targets for nitric oxide in the locust.

In the adult locust, nitric oxide (NO) synthase is expressed in interneurons that innervate mechanosensory neuropils, indicating that NO may participate in mechanosensory processing. Here, we have identified potential neuronal targets of NO by localizing the expression and activity of soluble guanylyl cyclase (SGC), its principal molecular target in the nervous system. We used two complementary approaches, namely immunolocalization of SGC alpha-subunit (SGCalpha), and of cyclic GMP (cGMP) after exposure to an NO donor. The cell bodies, axons and central projections of thoracic exteroceptors, proprioceptors, auditory receptors, and chemoreceptors were strongly immunoreactive for SGCalpha. Strong SGCalpha immunoreactivity also occurred in all thoracic motor neurons, including their axon terminals. NO-donors induced a pattern of cGMP immunostaining that was similar to the distribution of SGCalpha, indicating that both sensory and motor neurons contain functional SGC. Therefore, NO may modulate both the input from these sensory neurons and the output of motor neurons. Although the expression of SGCalpha was highly consistent, NO donors did not always induce cGMP-staining in SGC-containing neurons, suggesting that SGC is coregulated by factors other than NO. Complementing previous reports in the visual and olfactory system, our results indicate a general role for NO-cGMP signaling in early sensory processing; diffusible signals may mediate a cross-adaptation or -sensitization within neural maps where similarly tuned neurons have adjacent projections, an anatomical arrangement shared by many sensory systems.

Presynaptic nicotinic receptors modulating dopamine release in the rat striatum.

The modulation of striatal dopamine release by presynaptic nicotinic acetylcholine receptors is well documented for both synaptosomes and slices. Because the latter retain local anatomical integrity, we have compared [3H]dopamine release evoked by the nicotinic receptor agonists (-)-nicotine and (+/-)-anatoxin-a from striatal synaptosome and slice preparations in parallel. At higher agonist concentrations, mecamylamine-sensitive [3H]dopamine release was greater from slices, indicative of an additional component, and this increase was abolished by glutamate receptor antagonists. To begin to examine the localisation of specific nicotinic acetylcholine receptor subtypes in the striatum, immunogold electron microscopy was undertaken with the beta2-specific monoclonal antibody 270. In striatal sections, gold particles were associated with symmetric synapses (dopaminergic) but were absent from asymmetric synapses (glutamatergic). Surface labelling of striatal synaptosomes with gold particles was also demonstrated. Taken together, these results are consistent with dopamine release mediated by beta2-containing nicotinic acetylcholine receptors on dopamine terminals, while non-beta2-containing nicotinic acetylcholine receptors may enhance dopamine release indirectly by releasing glutamate from neighbouring terminals.

NADPH diaphorase-positive dendritic profiles in rat thymus are discrete from autofluorescent cells, immunoreactive for inducible nitric oxide synthase, and show strain-specific abundance differences.

Predisposition to autoimmune disorder in Lewis rats has been associated with abnormal hypothalamic regulation of circulating steroids, leading to inadequate suppression of T helper 1 (Th1) cell-mediated inflammatory reactions. In addition, autoimmune syndromes can be triggered within formerly resistant animals, following damage to the negative selection process of the thymus. A contribution to the autoimmune-susceptible phenotype may therefore derive from the status of thymic tolerance. One mechanism of intrathymic negative selection may involve nitric oxide. Because inducible nitric oxide synthase (iNOS) is known to be inhibitable by steroids, its expression might be different within strains having neuroendocrine disturbance. We report on a study to compare intrathymic iNOS expression in autoimmune-prone Lewis rats with other resistant strains. Interdigitating cells (IDC), darkly stained for diaphorase, were confirmed as immunoreactive for iNOS. They were located towards the medullary side of an accumulation of unstained, but autofluorescent cells (presumed to be macrophages) that circumscribes the corticomedullary zone. The role of iNOS+ IDC in the apoptotic deletion of T cells has been suggested by other studies. Despite the blunted steroidal condition reported for Lewis, nitrergic cell abundance was shown, by quantitative analysis of histochemical stain, to be on average approximately twofold lower compared with resistant strains (Fischer and Sprague-Dawley). This trend was evident in males and females, and confirmed by independent observers. We hypothesize that an intrathymic, iNOS-dependent mechanism may be important for the suppression of potentially autoreactive T-cell clones.

Localization of soluble guanylyl cyclase alpha-subunit in identified insect neurons.

The distribution of soluble guanylyl cyclase in the brain of the locust Schistocerca gregaria was analysed using antisera to a highly conserved region (X-peptide) of the Drosophila soluble guanylyl cyclase alpha-subunit (SGCalpha). Analysis of locust brain and locust eye homogenates in Western blots using X-peptide antisera revealed specific staining of a approximately 65 kDa band, which is similar to the expected molecular mass for a SGCalpha-subunit. SGCalpha-immunoreactivity was localized in identified neuronal components of several sensory systems including photoreceptors of the compound eyes and ocelli, large ocellar interneurons, antennal mechanosensory neurons and olfactory interneurons. These neurons are putative targets for the gas nitric oxide which activates guanylyl cyclase activity in the locust brain.

Nitric oxide synthase activity in malaria-infected mice.

Nitric oxide (NO) is implicated in a variety of major cellular functions including defence from invasion by microbical pathogens. Evidence has been presented suggesting that it is an important mediator of protection in the early non-specific responses to malaria in mice infected with Plasmodium chabaudi (Taylor-Robinson et al. 1993). Other data from in vitro studies on the asexual stages of human parasite Plasmodium falciparum indicated that while nitric oxide itself may not be inhibitory to parasite development, its downstream products do have some anti-plasmodial activity (Rockett et al. 1991) and these could be generated by macrophages (Gyan et al. 1994). Similarly, the sexual phases of both rodent (Motard et al. 1993) and human malaria (Naotunne et al. 1993) are reportedly susceptible to the toxic effects mediated by nitric oxide generated by blood leucocytes in the course of transmission to the mosquito vector.

Sexual development of malaria parasites is inhibited in vitro by the neem extract azadirachtin, and its semi-synthetic analogues.

We have shown that azadirachtin, a compound from the neem tree, Azadirachta indica, and selected semi-synthetic derivatives, block the development of the motile male malarial gamete in vitro. Changes in the hemiacetal group at position C11 in the molecule result in a loss of activity in this assay. The motility of fully formed male gametes, and other selected flagellated cells, is unaffected by azadirachtin in vitro. These findings raise the possibility of developing azadirachtin-based compounds as antimalarials with transmission-blocking potential, as well as permitting the further study of structure-activity relationships in these compounds.

Microcomputer system in an accident unit.

A microcomputer-based records system has been developed for use in the accident unit of a district general hospital. Patient details are entered directly at the reception desk and the computer generates a casualty card that is updated after the patient has been seen by the doctor, who determines the diagnosis to be recorded and specifies the injury coding. Information is stored on floppy discs, each holding the details of 3400 patients. The computer is used to produce a daily log-book of attendances, including revisits. The stored data may be examined and analysed for both administrative and medical purposes. The work load can be rapidly analysed according to various options that include the nature, type, and site of injuries. The system was introduced in December 1980. Location within the unit allows control over its operation, and many of the limitations of a manual system have been overcome.

Early experiences of ether anaesthesia in North Wales.

An account is given of the history of ether anaesthesia in North Wales during the early months of 1847. It demonstrates that the study of local newspapers can be of invaluable assistance to the medical historian.