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Biomedical subjects

D G Butler

Publications and source records attributed to D G Butler.

At least 37 records · Page 2Linked to original sources
PubMed1977

Human rotavirus enteritis induced in conventional piglets. Intestinal structure and transport.

To better understand the pathogenesis of infantile viral gastroenteritis, we studied Na+ and Cl- fluxes in vitro in short-circuited jejunal epithelium from 8-10-day-old piglets after infection with a standard dose of human rotavirus given via nasogastric tube. 11 infected piglets, all of whom became ill, were compared with 9 uninfected, healthy litter-mates. When killed 72 h after infection, intestinal villi were shorter and crypts deeper (P less than 0.025) in duodenum, upper jejunum, and mid-small intestine, but not ileum in infected piglets. Virus antigen was seen by fluorescence microscopy in occasional jejunal villus tip cells in only four infected piglets and no controls at 72 h. Net Na+ and Cl- fluxes did not differ from noninfected litter-mate controls under basal conditions, but response to glucose was blunted in infected piglets (P less than 0.001). Theophylline stimulated net Cl- secretion in both infected and control animals, and cyclic AMP concentration in isolated jejunal villus enterocytes did not differ significantly. In isolated jejunal villus enterocytes of infected piglets, thymidine kinase activity increased (P less than 0.001), and sucrase activity decreased (P less than 0.001). We conclude that in this invasive enteritis caused by a major human viral pathogen, glucose-coupled Na+ transport is impaired in the jejunum at a time when the villus epithelium shows enzyme characteristics of crypt epithelium, and when little or no virus is present. These findings are identical to those occurring in an invasive coronavirus enteritis of piglets but differ markedly from those seen with enterotoxigenic diarrhea.

Animals↗
PubMed1977

Transmissible gastroenteritis: sodium transport and the intestinal epithelium during the course of viral enteritis.

Sodium transport, mucosal structure, and epithelial enzymes were studied in piglets killed 10, 25, 40, 72, or 144 hr after infection with a standard dose of transmissible gastroenteritis virus. Glucose-stimulated Na transport measured in short-circuited jejunal epithelium and suspensions of villous enterocytes became progressively more abnormal during the first 40 hr, but recovered completely by 144 hr. As Na transport deteriorated, jejunal mucosal villi shortened and crypts deepened; cells isolated from the villi became more crypt-like in their enzyme profile, with high levels of thymidine kinase and low levels of sucrase activity 40 hr after infection. At 40 hr, when diarrhea is severe, little if any virus has been found in the epithelium. Our data suggest that the relatively undifferentiated crypt type enterocytes on the villi constitute an important determinant of altered Na transport and diarrhea in this invasive viral enteritis.

Animals↗
PubMed1976

Viral gastroenteritis: recent progress, remaining problems.

Infants and young children are particularly susceptible to a recently identified viral enteritis which is highly contagious and seems both common and universal. In this disease, virus invades the upper intestinal epithelium, causing acute diarrhoea with early fever and vomiting. We studied a similar disease in pigs, infecting three-week-old animals with transmissible gastroenteritis virus (TGE), which also invades the upper intestinal epithelium. In this model, diarrhoea is massive 16-40 hours after infection, when stools contain increased electrolytes but no excess of sugar. In the jejunum of intact pigs at the 40-hour stage we found altered Na+ and water flux, decreased mucosal activities of disaccharidases and Na+, K+-ATPase, but normal adenylate cyclase activity. At the same stage the response of Na+ flux to glucose was blunted in jejunal epithelium studied in Ussing short-circuit chambers and in suspensions of villous cells; Cl- flux responded normally to theophylline, and thymidine kinase and sucrase activities of cells isolated from jejunal villi were similar to those found in crypt cells. Probably by 40 hours after infection most virus has been shed from the mucosa. Viral diarrhoea clearly differs from enterotoxigenic diarrhoea. Consideration of its pathogenesis must take into account the dynamic nature of the mucosal epithelium and the factors governing differentiation of enterocytes as they migrate from crypt to villus. Sufficient information is available now to characterize one specific and apparently prevalent viral enteritis in man and to identify additional viral enteritides. There is hope that preventative therapy can be developed. Our understanding of the mechanisms of viral diarrhoea is limited, but the availability of an animal model and the promise of others makes us optimistic that these deficiencies can be remedied. Greater understanding of the pathogenesis of viral diarrhoea should better the active therapy of affected infants and children.

Animals↗
PubMed1976

The andrenocortical homolog in the lake sturgeon, acipenser fulvescens rafinesque.

The adrenocortical homolog in the chondrostean fish, Acipenser fulvescens, is confined within yellow corpuscles located at the dorsal junction of the two kidneys near the cardinal veins. The concentration and distribution of this tissue in chondrosteans appear to be a condition intermediate between that of cyclostomes and teleosts. The homology of this tissue to adrenocortical tissue of higher vertebrates is demonstrated in its delta5-3beta-hydroxysteroid dehydrogenase activity and the ultrastructure of the cells. The cells contain large lipid droplets and an abundance of smooth endoplasmic reticulum and mitochondria. The abundance of smooth endoplasmic reticulum, a large Golgi apparatus and an extensive elaboration of the plasma membrane suggest the high degree of steroidogenic activity of these cells. Apposed plasma membranes make contacts through the unique cell contacts described in the adrenocortical cells of mammals (Friend and Gilula, '72). The Golgi apparatus is described as a most conspicuous component of the cytoplasm and is presented as further evidence for the important involvement of this organelle in corticosteroidogenesis in vertebrates. These morphological observations are discussed in relation to the known secretory products of this tissue in the sturgeon, and it is suggested that there is a need for further examination of the corticosteroids produced by lower vertebrates.

Adrenal Glands↗
PubMed1976

Transmissible gastroenteritis. Mucosal ion transport in acute viral enteritis.

Ion transport in the jejunal mucosa of 14-to 16-day-old piglets with severe diarrhea 40 hr after infection with transmissible gastroenteritis (TGE) virus was studied. In infected pigs Na+ transport failed to respond normally to glucose when studied either in Ussing short-circuited chambers or in suspensions of enterocytes isolated selectively from jejunal villi. Theophylline, 10mM, added to the chambers produced the same brisk electrical responses and increments in net Cl- secretion in tissue from both infected and control groups. A defect in glucose-stimulated Na+ absorption in the acute stage of a viral enteritis has been identified which probably contributes to the impaired lumen-to-extracellular fluid flux of Na+ found previously in the jejunum of intact TGE-infected pigs. The mechanisms causing diarrhea in this invasive viral enteritis differ from those causing toxigenic diarrhea.

Acute Disease↗
PubMed1974

Transmissible gastroenteritis. Mechanisms responsible for diarrhea in an acute viral enteritis in piglets.

We studied 3-wk-old piglets 40 h after experimental infection with transmissible gastroenteritis (TGE) virus to identify the mechanisms of diarrhea in this disease and to better understand infectious diarrhea in humans. Using continuous segmental marker perfusion in four regions along the gut, we found significant increases in net intraluminal accumulation of water and electrolytes only in the proximal jejunum, the region infected by the virus. In this jejunal segment studied in vivo, unidirectional sodium flux, extracellular fluid (ECF) to lumen, significantly increased, lumen to ECF significantly decreased, compared with matchfed littermates. The standard perfusate rendered hypertonic by adding mannitol (450 mosmol/kg), in the same segment of normal pigs, caused only an increase in ECF to lumen flux of sodium. TGE did not alter gross villous structure or intraluminal bacteria, bile salts, lactate, pH, or osmolality. Epithelial cell migration was accelerated in the jejunum of infected pigs. Isolated in suspension, these cells from TGE pigs exhibited increased active and passive sodium efflux, cells from mannitol-perfused pigs exhibited only increased active sodium efflux. In this viral enteritis, altered sodium transport occurring in the jejunum, the region of the intestine infected appears to be associated with defective epithelial cell function. The precise nature of the abnormalities in sodium transport, their relationship to disturbances of transport of other solutes, and to virus epithelial cell interaction remain to be defined.

Animals↗