SUMMARY The pathogenicity of classical enteropathogenic Escherichia coli strains of human origin was investigated in gnotobiotic piglets. One to two day old piglets in groups of four were infected perorally with approximately 10 colony forming units of one of eight enteropathogenic E coli strains or a non-pathogenic control strain. Animals were necropsied 24 or 48 hours after infection and their intestines were subjected to histological examination, quantitative bacterial culture and estimation of lactase activity. Four enteropathogenic E coli strains caused mild to moderate diarrhoea in nine of the 16 piglets inoculated with them. Piglets given two of these strains later became moribund. One enteropathogenic E coli strain caused a severe illness unaccompanied by diarrhoea. Inflammation of the intestinal mucosa occurred with all eight enteropathogenic E coli strains, but not with the control strain. Pathological changes were most pronounced in the distal ileum and colon and adherent bacteria were seen on the surface of the inflamed mucosa. The extent of the inflammatory response in infected piglets for the most part paralleled the severity of the clinical signs, the degree of bacterial colonisation and the reduction in lactase activity. Electron microscopic examination of tissue from piglets infected with three different strains showed that bacterial adherence to the apical plasma membrane of epithelial cells was accompanied by distinctive ultrastructural changes. These included degeneration of the microvillous brush border, together with cupping and pedestal formation of the plasma membrane at sites of bacterial attachment. The same changes have been seen in naturally occuring enteropathogenic E coli diarrhoea in humans and rabbits. The combined clinical and pathological findings indicate that the neonatal gnotobiotic piglet is a suitable model of infection with enteropathogenic E coli.Escherichia coli is both the predominant member of the normal aerobic colonic flora and a prominent cause of gastroenteritis.

The relationship between the effects of isoproterenol and prostaglandin El (PGE1) on contractile state, cyclic AMP accumulation, and the activation states of protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37), phosphorylase kinase, glycogen synthase, and glycogen phosphorylase have been studied in the isolated perfused rat heart. Perfusion of hearts with isoproterenol (10 or 80 nM) caused enhancement of left ventricular dP/dt (P, pressure), increased intracellular cyclic AMP, increased the activation states of protein kinase, phosphorylase kinase, glycogen phosphorylase, and conversion of glycogen synthase to a less active form. PGE1 (2 or 30 ;&M) increased cyclic AMP accumulation and activated protein kinase, but caused no detectable changes in dP/dt or the activation states of the protein kinase substrates involved in glycogen metabolism. Perfusion of hearts with either 10 nM isoproterenol or 30 1sM PGE1 produced comparable increases in cyclic AMP accumulation and protein kinase activity. Exposure of hearts to a combination of these agents caused additive effects on cyclic AMP content and protein kinase activity. However, values for phosphorylase kinase, glycogen phosphorylase, glycogen synthase, and dP/dt did not differ from those observed in the presence of 10 nM isoproterenol alone. The failure of PGE1 to stimulate phosphorylation of protein kinase substrates was not due to an increase in phosphorylase phosphatase activity. We conclude that an increase in intracellular cyclic AMP and the subsequent activation of protein kinase are insufficient to change either the activities of phosphorylase kinase, glycogen phosphorylase, and glycogen synthase or the inotropic state of eart muscle. Kuo and Greengard (1) have advanced the idea that ubiquitous cyclic AMP-dependent protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) mediate most, if not all, of the effects of cAMP in eukaryotes (1-3). According to this hypothesis the ability of a hormone to elicit a response mediated by cAMP would be determined by the presence of the appropriate adenylate cyclase-linked receptor on the surface of the cell and by the presence within the cell of appropriate substrates for protein kinase. Thus, receptors specify the spectrum of hormonal sensitivity of a cell and available substrates specify the precise response. Much evidence supports the universality of Kuo and Greengard's hypothesis. It is apparent that cAMP is the only ligand necessary for the activation of protein kinase (4, 5). Numerous events, notably glycogenolysis (2) and lipolysis (6), result from phosphorylation of proteins by cAMP-dependent protein kinases subsequent to elevation of intracellular cAMP. Other than phosphodiesterase, the regulatory subunit of protein kinase appears to be the major high-affinity binding protein for cAMP (1). As noted by Rall, however, the protein kinase hypothesis presents us with "the unsatisfying picture of the catalytic subunit of protein kinase swimming about, happily phosphorylating a variety of cellula...

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Streptococcus durans was isolated from a foal with profuse watery diarrhea and caused a similar syndrome when inoculated into foals via the orogastric route. The most consistent and striking histological feature was the extensive colonization of the mucosal surface of the small intestine by S. durans. Associated mucosal changes were mild to modeate, and brush border lactase and alkaline phosphatase production were depressed. S. durans also induced acute diarrhea in young gnotobiotic piglets. Mucosal changes were mild and, as with foals, the mucosal surface of the small intestine was colonized by the organism.

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