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Biomedical subjects

A E Stuart

Publications and source records attributed to A E Stuart.

At least 19 recordsLinked to original sources

Weeding and grooming of pathogens in agriculture by ants.

The ancient mutualism between fungus-growing ants and the fungi they cultivate for food is a textbook example of symbiosis. Fungus-growing ants' ability to cultivate fungi depends on protection of the garden from the aggressive microbes associated with the substrate added to the garden as well as from the specialized virulent garden parasite Escovopsis. We examined ants' ability to remove alien microbes physically by infecting Atta colombica gardens with the generalist pathogen Trichoderma viride and the specialist pathogen Escovopsis. The ants sanitized the garden using two main behaviours: grooming of alien spores from the garden (fungus grooming) and removal of infected garden substrate (weeding). Unlike previously described hygienic behaviours (e.g. licking and self-grooming), fungus-grooming and garden-removal behaviours are specific responses to the presence of fungal pathogens. In the presence of pathogens, they are the primary activities performed by workers, but they are uncommon in uninfected gardens. In fact, workers rapidly eliminate Trichoderma from their gardens by fungus grooming and weeding, suggesting that these behaviours are the primary method of garden defence against generalist pathogens. The same sanitary behaviours were performed in response to the presence of the specialist pathogen Escovopsis. However, the intensity and duration of these behaviours were much greater in this treatment. Despite the increased effort, the ants were unable to eliminate Escovopsis from their gardens, suggesting that this specialized pathogen has evolved counter-adaptations in order to overcome the sanitary defences of the ants.

Animals↗

Repellent and antifeedant activity of salicylic acid and related compounds against the biting midge, Culicoides impunctatus (Diptera: Ceratopogonidae).

An artificial membrane, blood-feeding method was used to assess the repellent and antifeedant effects of derivatives of salicylic acid on the biting midge Culicoides impunctatus Goetghebeur. Trans-2-hydroxycyclohexanecarboxylic acid, 6-methylsalicylic acid, 2,6-dihydroxy-4-methylbenzoic acid, and salicyluric acid caused highly significant inhibition of feeding, with salicyluric acid performing significantly greater than the other compounds. Investigating the effects of alkyl substitution of salicylic acid, o-thymotic and o-cresotic acids were also effective. A pilot clinical trial using salicyluric acid indicated that it provided a protective effect and it was hypothesized that this may have resulted primarily from contact, because no significant repellent effects were shown for this compound in a microscope slide test, designed to demonstrate repellency with volatile compounds.

Animals↗

Proust, memory and the Engram.

The French novelist Marcel Proust (1871-1922) was born at Auteuil, Paris and was a semi-invalid all his life, cosseted by his mother until her death in 1905 when he was 34 years old. His hitherto 'social butterfly' existence was transformed. He withdrew himself from society and lived in a sound-proof flat giving himself entirely to introspection. Delving into the 'self' below the levels of superficial consciousness, he set himself to transforming into art the realities of experience as known to the inner emotional self. In his monumental 13 volume novel, A la recherche du temps perdu, it is evident how no detail ever escapes the amazingly observant eye of the artist, and how his experience is subjected to close scrutiny and a searching analysis. His characters are described in terms of their concealed emotional lives, evolving in a plane that has nothing to do with temporal dimensions.

Emotions↗

Uptake of precursor and synthesis of transmitter in a histaminergic photoreceptor.

As a first step in understanding how the supply of the neurotransmitter histamine is maintained in a photoreceptor, we followed the uptake and metabolism of the immediate precursor of histamine, histidine. [3H]Histidine taken up into photoreceptors and glia was detected using autoradiography, and synthesis of [3H]histamine from [3H]histidine was assayed with thin-layer chromatography. Photoreceptors from barnacles were pulsed (15 min) with [3H]histidine (0.2-200 microM), then maintained in normal saline for up to 24 hr. Autoradiography showed that photoreceptor somata, axons, and presynaptic arbors were labeled, but only weakly, like (nonhistaminergic) ganglion cells. Label instead was concentrated over surrounding glia. Stimulating preparations with light did not increase photoreceptor labeling. Grain counts from photoreceptor axons showed uptake of [3H]histidine into these neurons by a Na+-dependent mechanism with a Km of approximately 50 microM. Over 24 hr only 1% of the [3H]histidine taken up by preparations was converted to [3H]histamine either in the dark or in the light. Injections of [3H]histidine directly into photoreceptors established that synthesis takes place within the photoreceptors and confirmed that stimulation with light did not measurably affect the rate of conversion of [3H]histidine to [3H]histamine. These results suggest that de novo synthesis of transmitter is unlikely to be as important as its reuptake in maintaining neurotransmitter supply in these photoreceptor terminals. In support of this conclusion, photoreceptors accumulated more label when transmitter release was stimulated with high K+ and histamine uptake was antagonized with chlorpromazine.

Animals↗

Selective, activity-dependent uptake of histamine into an arthropod photoreceptor.

The synapses made by many arthropod photoreceptors are disinhibitory and use histamine as their transmitter. Because decreases and not increases in the cleft concentration of transmitter constitute the important event at these synapses, a transporter to clear the cleft of histamine would seem particularly crucial to signal transfer. We report here that 3H-histamine is taken up selectively into barnacle photoreceptors by a Na+-dependent mechanism, presumably a transporter. Using light microscopic autoradiography, we observe heavy label over axons and presynaptic terminals of these neurons when they are stimulated during uptake. The radioactivity taken up was identified as 3H-histamine by thin layer chromatography; no metabolites were detected, even after 5 hr. Radiolabeled 5-hydroxytryptamine and GABA are not taken up by the photoreceptor. 3H-histamine uptake into photoreceptors is decreased markedly by an excess of unlabeled histamine and by chlorpromazine and phenoxybenzamine. Unexpectedly for uptake dependent on the NA+ gradient, photoreceptor terminals label more intensely in the light (when depolarized) than in the dark (when hyperpolarized). Glia label more strongly than photoreceptors in dark-incubated preparations. The presence of presynaptic uptake strengthens the evidence that histamine is the neurotransmitter of arthropod photoreceptors and provides a mechanism by which this synapse could recycle transmitter, control its steady-state cleft concentration, and clear it from the cleft in response to decreases in its release from the photoreceptors.

Animals↗

The biting midge of the West Highlands: fifty years of research.

The biting midge of the West Highlands belongs to the family Ceratopogonidae and approximately 150 species are known to exist in Britain. All of the flies are of minute size and slender build with wings which fold over the back. The females have biting mouthparts including a needle sharp proboscis with scissor type mandibles. The males do not bite. The Ceratopogonidae devours other small insects, some feed on plant juices, others pierce the wing veins of butterflies and some attack juicy caterpillars. Only three genera are bloodsuckers and of these only Culicoides occurs in Britain. The members of this genus are classified by the pattern of wing venation and the spots on the wings. Edwards' gives a detailed table of these characteristics. The commonest species in Scotland is C. impunctatus, although others have been met with on Skye.

Animals↗

Dynamics of intracellular free calcium concentration in the presynaptic arbors of individual barnacle photoreceptors.

At photoreceptor synapses, transmitter release is continuous and graded. At this type of synapse, the control of presynaptic [Ca2+]i and calcium's role in releasing transmitter might be different than at terminals invaded by all-or-none action potentials. To examine this possibility, we measured the spatial and temporal changes of [Ca2+]i in response to depolarization of individual photoreceptor terminals of the barnacle Balanus nubilus, which had been injected with the Ca2+ indicator Fura-2. Depolarizing pulses produced voltage-dependent Ca2+ entry that was confined to the tips of the arbor where the release sites are located. At increasing distances from the tips, the rate of [Ca2+]i increase was slower and the peak [Ca2+]i occurred later, suggesting that Ca2+ entered the tips and diffused back into the larger processes of the arbor. Consistent with this result, a stable gradient of [Ca2+]i was observed at maintained depolarizations, with the highest values at the tips of the arbor. Removal of external Na+ did not affect the time course of Ca2+ decline in the terminal, indicating that Na+/Ca2+ exchange was not the primary mechanism for restoring [Ca2+]i to basal levels. Computer simulations, assuming only Ca2+ entry at the arbor's tips and diffusion of Ca2+ away from the entry site, qualitatively reproduced these observations. The threshold for Ca2+ entry was near -60 mV, and entry was maintained during prolonged depolarizations, in agreement with previous experiments showing that Ca2+ channels in the terminal region do not inactivate. The time course of the measured [Ca2+]i change in the terminal paralleled voltage changes due to a Ca(2+)-activated K+ conductance, which senses [Ca2+]i just under the membrane. This parallelism is expected since the release sites are located on processes of small-enough diameter to permit radial equilibration of [Ca2+]i within the time course of physiological voltage changes. Therefore, the optical measurements reflect the mean level of [Ca2+]i under the membrane. Whether this mean concentration is also the value at the sites that trigger exocytosis will depend on how close the Ca2+ channels are to these sites.

Action Potentials↗

Histamine: a putative afferent neurotransmitter in Limulus eyes.

Histamine has been proposed as a photoreceptor neurotransmitter in two major groups of arthropods, the insects and the crustacea. In this study biochemical and immunocytochemical approaches were used to examine the synthesis, endogenous content, and cellular distribution of histamine in the visual system of the horseshoe crab Limulus polyphemus, an ancient chelicerate arthropod. Studies with this animal have been critical to our understanding of the basic processes of vision. High-voltage paper electrophoresis was used to assay for histamine synthesis in Limulus tissues incubated with radiolabeled histidine; histamine synthesis was detected in the lateral, median, and ventral eyes and optic nerves and in the visual centers in the brain. Endogenous histamine, assayed as its orthophthalaldehyde derivative by high-performance liquid chromatography and electrochemical detection, was also detected in these tissues. Immunocytochemical analyses, with an antiserum directed against a protein conjugate of histamine, revealed histamine-like immunoreactivity in the somata of photoreceptors in each of the eyes and in the regions of the brain where the photoreceptors terminate. Histamine-like immunoreactivity was also intense in the cell bodies and axon collaterals of eccentric cells in the lateral eye and in eccentric cell projections in the brain. These results show that histamine is a major biogenic amine in the Limulus visual system, and they suggest that this amine is involved in transmitting visual information from the eyes to the brain and in lateral inhibition, a fundamental mechanism for processing visual information in the lateral eye.

Afferent Pathways↗

Pathology and clinical features of gastro-intestinal lymphoma in Saudi Arabia.

The histopathology and clinical presentation of 19 cases of primary gastrointestinal lymphoma is described. Our patients are similar to others in the Middle East but have a lower incidence of diarrhoea and malabsorption. All revealed a widespread chronic inflammatory background. Four patients with primary gastric lymphoma had endoscopic biopsies from the duodenum; these biopsies were completely free from tumour but showed a moderate to severe diffuse lymphoplasmacytic infiltrate. Electron microscopy shows that tumour cells penetrate basement membranes and invade the epithelium which becomes thin and attenuated. Substances which inhibit lymphocyte tropism might be useful in preventing intestinal ulceration. The MALT concept has been found useful in classification of the tumours. Two patients with unusual mesenteric node histology are described and it is thought that the appearances may indicate a substantial capacity for differentiation in the group of tumours.

Adult↗

Histamine: the case for a photoreceptor's neurotransmitter.

The evidence is strong that histamine is the transmitter from photoreceptors of the barnacle, several insect species, and Limulus. Histamine is synthesized and stored in the photoreceptors and mimics the effect of the natural transmitter on the postsynaptic cell. An activity-dependent uptake mechanism exists to recapture the histamine for reuse at this continuously active synapse. Only light-dependent release of this compound remains to be demonstrated. A primary job of the photoreceptor's synapse in the barnacle and also in insects is to convert photoreceptor hyperpolarizations at the offset of light (which presumably lead to decreases in transmitter release) to a depolarizing off-response in the postsynaptic cell. Hardie (10) has established that histamine has cooperative binding and a relatively low affinity for its receptor, leading to a short open time for the postsynaptic channel. These features could allow the postsynaptic cell to respond relatively quickly to decreases in transmitter concentration. Perhaps the uptake mechanism demonstrated in barnacle photoreceptors will also prove to be important in the generation of the postsynaptic response by quickly clearing the cleft of released histamine. It will be of interest to determine what factors control the rate of uptake of histamine and whether blocking the uptake mechanism affects signals set up in the postsynaptic cell.

Animals↗

Characteristics of neurones projecting from the supraoesophageal ganglion in the shadow reflex pathway of the barnacle.

Barnacles respond to decreases in light intensity (shadows). Previous evidence indicates that the first stages of the visual pathway within the supraoesophageal ganglion comprise a limited number of neurones: a single pair of second-order neurones (I-cells), a pair of third-order projection neurones (A-cells), and at least five other projection neurones (four A-like shadow-excited cells and one shadow-inhibited cell) whose spikes may be recorded extracellularly from the circum-oesophageal connective nerve. Here we present evidence that information in this pathway diverges at the A-cell stage. Destruction of both A-cells by intense illumination of cells injected with carboxyfluorescein abolishes all shadow-evoked activity in the connectives and also the ability of shadows to influence motor neurones in the ventral ganglion. In addition, we have located the somata of these previously unidentified projection neurones, injected them with carboxyfluorescein, and observed that they have distinct branching patterns different from that of the A-cell. We name these cells 'alpha' (alpha), 'beta' (beta) and 'gamma' (gamma) cells. Simultaneous impalements show that A-cells drive at least one of the beta-cells but not vice versa. The same observation has not yet been made with regard to alpha- or gamma-cells. Depolarizing an I-cell does not readily drive a beta-cell impaled simultaneously. These observations support our conclusion that information diverges from the A-cells and not from the second-order I-cells to the other projection neurones in this ganglion.

Action Potentials↗

Combination chemotherapy for primary small intestinal lymphoma in the Middle East.

Twelve patients with primary small intestinal lymphoma were followed prospectively for 3 years. Endoscopic abnormalities were diagnostic of lymphoma in all cases where the duodenum was involved (83%). In three cases (25%) the disease extended to the stomach. One patient (8%) had diffuse small cell cleaved and 11 (92%) diffuse large cell lymphoma stages I (8%), II (25%), III (58%) and IV (8%). Nine of them were unresectable and primarily treated with combination chemotherapy; 67% achieved complete remission, 22% partial response and 11% no response. Only one patient relapsed and achieved a second remission. All complete remission patients are currently alive and free of disease at a median follow-up of 36 months. Overall survival for all patients is 58%, and disease-free survival is 50%. No instance of chemotherapy-related bleeding or perforation was seen. Tetracycline was necessary for the treatment of IPSID-associated diarrhea and malabsorption in spite of cytotoxic chemotherapy.

Adult↗

Immunocytochemical evidence for the presence of histamine and GABA in photoreceptors of the barnacle (Balanus nubilus).

Biochemical evidence indicates that GABA and histamine may both be synthesized by barnacle photoreceptors (Koike & Tsuda, 1980; Timpe & Stuart, 1984; Callaway & Stuart, 1989b). We used antisera against GABA- and histamine-protein conjugates to determine whether the photoreceptors contain either or both of these antigens. Both antisera labeled all of the photoreceptors in each of the three ocelli. Histamine-like immunoreactivity was found throughout each photoreceptor cell but was most intense at their presynaptic terminals. Histamine-like immunoreactivity was blocked by preincubation of the antibody either with histamine or with a histamine-protein conjugate. GABA-like immunoreactivity was found in all parts of the photoreceptors including the cell body, axon, rhabdomeric dendrites, and presynaptic terminals. GABA-protein conjugates blocked the GABA-like labeling of the photoreceptors, while protein conjugates with histamine, L-glutamate, L-glutamine, beta-alanine, and taurine did not. Histamine-like immunoreactivity in the supraesophageal ganglion was confined to the photoreceptor terminals and a second, loose plexus of endings in the main neuropil. GABA-like immunoreactivity, in contrast, was found in approximately twenty-five pairs of neurons of this ganglion. In the cirral nerves, which are expected to contain inhibitory motoneurons, unidentified axons also labeled with the GABA antiserum.

Animals↗

Comparison of the responses to light and to GABA of cells postsynaptic to barnacle photoreceptors (I-cells).

We tested the hypothesis that gamma-aminobutyric acid (GABA) is the transmitter released by barnacle photoreceptors onto postsynaptic cells (I-cells). GABA was applied to I-cells either by superfusion or by ejecting it with pressure from a pipette positioned close to the I-cell's soma. The I-cell's response to GABA was compared with its response to light (i.e. to the photoreceptors' transmitter) by recording intracellularly from its soma. Bath-applied (100 microns to 10 mM) and pressure-applied GABA (10 mM in pipette) hyperpolarizes I-cells by increasing their conductance, as does the photoreceptors' transmitter. The response to pressure-applied GABA consists of two components; both persist when Co2+ or Cd2+ are added to the saline to block synaptic transmission in the preparation, indicating that GABA affects the I-cell directly rather than affecting a presynaptic cell. GABA hyperpolarizes the I-cell when applied to the cell over the soma and ipsilateral arbor or over the contralateral arbor. The I-cells' responses to GABA and to light both depend on extracellular K+ and are affected by changes in intracellular and extracellular Cl-. However, picrotoxin and beta-guanidinopropionic acid block the response to pressure-applied GABA but do not block the response to light even at an order of magnitude higher concentration. Thus, GABA is not likely to be the transmitter that causes the hyperpolarizing response of the I-cell. It may be a neuromodulator or the transmitter of an unknown input to the I-cell.

Animals↗