Analysis of pairs of individual Ia-E.P.S.P.S in single motoneurones.

1. Recordings of individual e.p.s.p.s evoked by the action of single medial gastrocnemius Ia fibres have been made from medial gastrocnemius motoneurones. In many motoneurones the action of two Ia fibres has been observed and the properties of the e.p.s.p.s compared. 2. For sixty-three pairs of averaged e.p.s.p.s, each from the same motoneurone, the ratio of half-widths was plotted against the ratio of rise times. These results were compared with theoretical values derived from the Rall compartmental model. It was found that variations in synaptic current time courses and differences in the termination of localized synaptic terminals were not sufficient to account for all the data. 3. Amplitude and rise time were inversely related but the correlation coefficient was very low. For pairs of e.p.s.p.s in the same motoneurone the e.p.s.p. with the fast rise time was larger than that with the slow rise time in forty-eight of sixty-three cases. 4. In a given motoneurone individual e.p.s.p.s evoked by the action of different Ia fibres did not vary greatly in amplitude. The ratio of peak amplitudes was less than 3 for 86% of the pairs of e.p.s.p.s examined, and the maximum was 4-8. 5. Amplitude histograms were constructed for individual e.p.s.p.s at thirty-three synapses. Twenty-two of them could be shown to satisfy the Poisson law. The others satisfied the binomial law or neither. 6. Within a given motoneurone the amplitude of an e.p.s.p. is closely related to the mean number of quanta released but not to the amplitude of the unit e.p.s.p. produced by the action of a single quantum of transmitter.     

Neural control of circulation in Aplysia. III. Neurotransmitters.

In the abdominal ganglion of Aplysia californica, seven motoneurons have been described which modulate the myogenic heart beat and vasomotor tone (28). These neurons mediate their motor effects by chemical transmission. In this paper we have attempted to specify the transmitters of six of these motoneurons. We have 1) studied the effects of several common transmitters on the innervated structures and compared these effects with the effects of firing the motoneurons, 2) examined whether blocking agents influence similarly the effect of a putative transmitter applied to the innervated structure and the effect of firing a motoneuron, and 3) tested the capability of the motoneurons to synthesize the putative transmitters from precursors. The positive inotropic and chronotropic effects of firing the excitor motoneuron RB(HE) were mimicked by perfusion of the heart with serotonin at a low concentration. Cinanserin blocked both the effects of motoneuron excitation and serotonin perfusion. RB(HE) was also shown to synthesize [3H]serotonin from L-[3H]tryptophan injected directly into the cell body. The effects of firing the two LD(HI) heart-inhibitory motoneurons were mimicked by perfusion of the heart with acetylcholine. Benzoquinonium blocked the effects of the inhibitory motoneuron and acetylcholine perfusion. Perfusion with arecoline also inhibited the heart beat. Acetylcholine applied to the arteries mimicked the vasoconstriction caused by the LB(VC) motoneurons. Aortic constriction in response to activity in LB(VC) cells or to acetylcholine was blocked by hexamethonium and curare. The heart inhibitor and vasoconstrictor motoneurons synthesized [3H] acetylcholine from [3H] choline injected into their cell bodies. Thus, as in vertebrates, acetylcholine mediates inhibition to the heart. Unlike vertebrates, however, serotonin mediates excitation to the heart and acetylcholine mediates peripheral vasoconstriction.     

Sociocultural aspects of epilepsy in Madagascar. K.A.P. survey carried out in Antananarivo

A general population survey on knowledge, attitudes and practices (K.A.P.) concerning epilepsy was conducted from 1st July to 31st December 1997 in Antananarivo, a region representative of ecological and cultural patterns of the Malagasy "Highlands". The sample, randomly selected according to the two-step cluster method, recruited 1392 men and women aged 18 years and older who were interviewed with a 16-item questionnaire. Knowledge and practices have significantly evolved since 1983, when a similar study was conducted. More natural explanations are given for the condition and health-care seeking is more common. However, popular attitudes towards the epileptic patient remain contradictory: the majority of those interviewed claimed to be tolerant; work and marriage could be envisaged for the epileptic patient, but not total freedom of movement nor regular school attendance. A more active popularisation of the disease thus appears to be necessary. Since some 60% of people had a radio, broadcasting and church involvement would be the most effective means towards this end. Traditional practicer do not seem to have an overwhelming influence; rather, healthcare seeking behaviour was determined by the availability of service, the efficacy of the intervention and cost. To be representative of Madagascar as a whole, our data should be compared to those of other surveys in more culturally enclosed and disadvantaged areas.     

Route of lymphocyte migration in pigs. I. Lymphocyte circulation in gut-associated lymphoid tissue.

Evidence is presented which indicates that recirculating lymphocytes originating from the intestine in pigs are returned to the blood circulation at the level of the mesenteric lymph nodes (MLN) and not via efferent intestinal lymph. This was demonstrated by three observations: (1) removal of all MLN resulted in a thirty-fold increase in lymphocyte numbers in efferent lymph of pigs, but not in rats; (2) there are about twenty-five times more lymphocytes in afferent intestinal lymph than efferent intestinal lymph in normal pigs; (3) 51Cr-labelled lymphocytes injected into afferent lymphatics are mostly recovered in the node tissue or efferent lymph of sheep, and very few in the venous drainage, whereas in pigs relatively few labelled cells are recovered in the node or in efferent lymph.     

The role of platelets in infections. I. Observations in human and murine malaria.

The interaction between platelets and microorganisms may be underestimated. Our in vivo studies support a direct role of thrombocytes in malarial infections. We have found intrathrombocytic parasites of Plasmodium vivax (in 10% of men naturally infected) and P berghei (in 53% of mice experimentally infected); these were both merozoites and trophozoites. Neither the mechanism of parasitization (whether by active penetration or by phagocytosis) nor the outcome of this phenomenon is known. However, structures suggestive of partially digested parasitic material were seen in platelets of almost 50% of the men and 75% of the mice. These findings suggest that other microoganisms (fungi, bacteria, and viruses) may also enter thrombocytes in vivo. If so, platelets could play important roles, either favorable or deleterious, in infections.     

Dirofilaria immitis. 5. Immunopathology of filarial nephropathy in dogs.

Fourteen beagles infected with larvae (microfilariae) of Dirofilaria immitis, were randomly selected from another study in which the toxic effects of subfilaricidal doses of diethylcarbamazine were being evaluated. This group of 14 dogs, together with 4 uninfected control animals, were variably sacrificed between 14 and 25 months after larval inoculations, and the ensuing renal lesions were studied by light and ultrastructural microscopy and by immunofluorescence and antibody elution techniques. On the basis of these studies, two groups of animals were distinguished. The first group was characterized by a striking pattern of linear fluorescence and fine ultrastructural dense deposits along the glomerular basement membrane, poor antibody response, and an inability to clear microfilariae from the tissues and circulation. The second group, with a nonlinear pattern of fluorescence, was characterized by a strong immune response, efficient elimination of microfilariae, and immunofluorescence and ultrastructural evidence of predominantly mesangiopathic immune complex renal disease. In both groups, elution studies demonstrated tissue deposits of antiworm antibodies, suggesting a filaria-antibody immune-complex nephropathy. No evidence was found for the presence of anti-basement-membrane antibodies. On the basis of a previous experimental model, it is postulated that in the first group of animals with linear fluorescence, the observed lesions may represent a natural form of an immunopathogenic mechanism of glomerular damage in which filarial antigen becomes uniformly localized in the glomerulus and elicits an autologous antibody response. The possible role of the drug diethylcarbamazine in inducing this mechanism of immune injury is discussed.     

Alteration of enzymes in ageing human fibroblasts in culture. V. Mechanisms of glutathione peroxidase modification.

Ageing of WI-38 fibroblasts in culture was used as a model in order to investigate the evolution and the alteration of the key antioxidant enzyme glutathione peroxidase. The activity of glutathione peroxidase is influenced by the presence of selenium in the culture medium and we have also shown that the specific activity of this enzyme does not decrease during ageing, but rather slightly increases. No alteration could be detected by immunotitration. Also the kinetic parameter Km for tert-butyl hydroperoxide has not changed. However, the heat resistance of the enzyme dramatically decreases with ageing. Dilutions of the enzyme preparations had the same influence on the thermosensitivity of the enzyme. This dilution effect is most probably linked to the dissociation of the enzyme subunits into dimers and monomers. Moreover, the kinetic of thermoinactivation curves are best explained by consecutive reactions of inactivation with an intermediary enzyme form. These observations strongly support the hypothesis that ageing is associated with an increased dissociation constant of the tetrameric glutathione peroxidase leading to an easier dissociation of the enzyme in old cells.