A total of 512 people from a defined population in west

The substantia nigra (SN) is crucial to the propagation of seizures in kindled rats and in other experimental seizure models. However, the mechanisms by which the SN acts to facilitate the propagation of seizures are unknown. To investigate these mechanisms we quantified the activity of SN neurons during seizures in kindled and naive rats in a paralyzed, ventilated state and examined the relationship between activity of neurons in the SN and the seizure-facilitating action of this structure. Our principal findings were that the majority of both SN dopamine and SN pars reticulata neurons, in kindled rats, fired in bursts temporally correlated to EEG waveforms recorded outside the SN during seizures; this response was only rarely found in SN neurons of naive rats during seizures elicited by stimulation of the amygdala; unlike kindled rats, lesions of the SN in naive rats did not suppress seizures. The finding that SN neurons fired in bursts during seizures in kindled, but not naive, rats indicates that seizure activity propagated into SN only in kindled rats. The correlation between seizure-suppressant effects of lesions and SN activation during seizures leads us to propose that one mechanism by which the SN promotes seizure propagation involves SN activation and transmission of seizure activity to targets of SN.

Background-Sera of patients with coeliac disease, containing IgA and IgG antigliadin antibodies (AGA) and various IgA autoantibodies, react with isolated enterocytes. AGA cross react with enterocyte antigens, one of which has been identified as calreticulin. Aims-To characterise the antigenic structures of gliadin, enterocytes, and calreticulin recognised by AGA from patients with active coeliac disease. Methods-AGA were isolated from sera of nine patients by aYnity chromatography and tested by competitive ELISA using 40 -gliadin synthetic dodecapeptides (A1-F6). Results-Reactivity of gliadin with all purified AGA tested was inhibited by peptide A4 at the N-terminal region; by C2, C3, and D4 at the central region; and by F3 and F4 at the C-terminal region of the gliadin molecule. AGA cross reactivity with enterocytes was inhibited by peptides A4, D1-D4, and F6 and with calreticulin by peptides A4, D3, and D4. As dominant epitopes AGA of coeliac patients recognise similar structures corresponding to peptides A4, D3, D4, and F6 present on gliadin, enterocytes, and calreticulin. Substitution of glutamine in the A4 peptide by glutamic acid caused loss of inhibitory capacity. Shortening of peptide A4 on the N-terminal by three amino acids increased its inhibitory eVect. Conclusions-AGA of patients with coeliac disease react with similar structures on gliadin and potential autoantigens on enterocytes. (Gut 1999;44:168-173)