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ABSTRACT. Peptic-tryptic-Cotazym (PTC) digests were obtained, simulating in vivo protein digestion, from rice, maize, rye, oats, barley, and sorghum prolamines and tested on small intestine cultures from rat fetus. The PTC digests of the prolamine fractions from rice and maize, even when tested at a concentration as high as 0.5 mg/ml, did not affect in vitro differentiation and maturation of fetal rat jejunum that took place in vitro in a way comparable to what happens in vivo. On the contrary, the PTC digests of prolamines from rye, oats, barley, and sorghum were very active in slowing down in vitro development of fetal rat intestine. These results further strengthen earlier findings and all together show that there is a strong correlation between toxicity results of cereal and/or cereal components assessed with clinical trials or in vitro systems based on bioptic specimens of intestinal mucosa from celiac patients and with the culture of rat fetal intestine. Therefore, the rat fetal intestine culture is considered to be an adequate model for screening and investigating cereal peptides which are toxic for the celiac small intestinal mucosa. 18:1372-1378, 1984) Abbreviations PTC, peptic-tryptic-cotazym GP, gliadin peptides Celiac disease is an enteropathy occumng in genetically predisposed individuals (about 0.5/1000 of the general population) when wheat is a component of the diet. Under such circumstances, diarrhea and several malabsorption symptoms are observed in association with intestinal mucosa atrophy. Soon after the discovery that wheat is the environmental factor triggering the appearance of malabsorption symptoms, it was demonstrated that wheat toxicitv resulted from the gliadin protein fraction and that the other w h a t protein fractions, i.e. albumins, globulins, and glutenins, were harmless (6, 64, 65, 67). Later on it was shown (27, 28) that the ingestion of peptide mixtures obtained from wheat gluten after in vitro sequential digestion with proteolytic enzymes also induces the typical symptoms in patients affected by celiac disease. Moreover, clinical trials have shown Received July 29. 1983; February 7. 1984. Address correspondence to Salvatore Auricchio. Clinica Pediatrica, I1 Facolti di Medicina e Chirugia. Via Sergio Pansini 5 , 8013 1 Naples, Italy. This paper is dedicated by the authors to Professor Francesco Pocchiari on the occasion of his 60th birthday. (Pediatr Resthat, in addition to wheat, rye, barley, and probably oats also have toxicity (7, 41), whereas rice and maize are considered nontoxic and are usually used as wheat substitutes in the diet of celiac patients. It is presumed, but not demonstrated, that toxicity of cereals other than wheat is associated with prolamine fractions equivalent to gliadins in the grain of these other species.The detection and characterization of cereal components that are toxic in celiac disease are very difficult because no animal models exist for this disease. Falchuk et al. (19,20) have proposed the organ culture of human small intestinal biopsie...

Ultraviolet difference absorption spectra of cholera toxin and its B protomer produced by the oligosaccharide moiety of the monosialoganglioside GM1 were measured as a function of the oligosaccharide concentration. In the presence of oligosaccharide, the spectrum is characterized by three peaks at 282, 288, and 292 nm. A linear increase in difference absorption was observed at these wavelengths vs. oligosaccharide concentration; a saturation effect occurred when the molar ratio of oligosaccharide to cholera toxin was higher than 5. The features of the spectra indicated that the binding with the oligosaccharide affected the environment of tryptophan and tyrosine residues of protomer B. In good agreement with the above results, circular dichroic spectra indicated also a local effect of the binding, mostly restricted to protomer B, while the residues of protomer A remained largely unperturbed. Difference absorption spectra were also measured for cholera toxin in the presence of ganglioside and detergent micelles. The employed gangliosides GD1a and GT1b, unable to bind cholera toxin, interact with the protein by way of contaminating traces of GM1. The preparations of GD1a and GT1b contained 0.8-1.0% (w/w) and 0.4-0.5% (w/w) of GM1, respectively. The results obtained with ganglioside GD1a and GT1b in contrast with the observations made with the oligosaccharide of GM1 indicated a major conformational change of the toxin structure. Upon comparison of the conformational change induced by ganglioside micelles with that induced by sodium dodecyl sulfate it may be suggested that the ganglioside micelle, behaving as a detergent, alters the structure of the toxin such as to induce the penetration of protomer A into the lipid milieu.(ABSTRACT TRUNCATED AT 250 WORDS)

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