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J W Robinson

Publications and source records attributed to J W Robinson.

At least 73 records · Page 4Linked to original sources

[Functional changes after occlusion of the colon in the dog].

One or two weeks after total mechanical occlusion of the dog colon, the organ is severely dilated, but the intraluminal pressure never exceeds 8 cm of water, and there are no obvious histological lesions of the mucosa. Perfusion of the occluded colon in vivo reveals marked inhibition of ion and water absorption; however, except in the case of potassium, net secretion as occurs in the occluded ileum does not develop. Glucose absorption in vivo and active phenylalanine and beta-methyl-D-glucoside transport in vitro are reduced in the mucosa of the occluded colon.

Animals↗

The kinetics of sodium-dependent phenylalanine influx in the intestine of the dog: a comparison between ileum and colon.

The kinetics of sodium-dependent phenylalanine influx into samples of dog ileal and colonic mucosa in vitro have been compared and contrasted. The data were evaluated by non-linear regression analysis, on the assumption that the total influx of the amino-acid is made up of the sum of a single saturable and a diffusive component. In both mucosae, the principal effect of changing the sodium concentration in the incubation medium was to alter the Kt for phenylalanine influx. The results were compatible with a general non-compulsory model for the formation of a ternary complex between the carrier, a phenylalanine molecule and a sodium ion which can be formed from either binary complex, i.e., either species can combine first with the carrier. Within the context of this model, it was shown that the Vmax for phenylalanine influx was substantially smaller in the colon than in the ileum. In addition, the constants governing the dissociation of the ternary complex into either binary complex were both significantly smaller in the colon, whilst the dissociation constants of the binary complexes were similar in the two regions of the intestine.

Animals↗

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Financial Management↗

Interactions between tryptophan, phenylalanine and sugar transport in the small intestinal mucosa.

The kinetics of the influx of tryptophan and phenylalanine into guinea-pig intestinal rings have been examined. The transfer of these two amino acids can be described by a single transport system, each amino acid having an affinity constant, Kt, of about 4 mM for the influx mechanism. Mutual inhibition studies have shown that the inhibitory constant of each of the amino acids is also 4 mM. Although fully competitive inhibition between the two amino acids occurs, the inhibition of the influx of the amino acids by sugars exhibits kinetics of the "pseudo-competitive" type. Such behaviour is compatible with an allosteric interaction between two different binding sites, one for each class of compounds. The lack of correlation between the inhibitory potency of a given sugar and its rate of transfer, as testified by a comparison of the effects of galactose and beta-methyl-glucoside on phenylalanine influx, can be reconciled with the "allosteric-interaction hypothesis", but specifically repudiates any theory that attempts to explain such interactions in a way that requires such a correlation. The fact that allosteric interactions are retained in cells preloaded with sodium also precludes a primary role for sodium in the mechanism of such interactions.

Animals↗

Structural and functional alterations in the mucosa of self-filling intestinal blind loops in rats.

1. Self-filling blind loops of jejunum were constructed in three groups of rats; in the first, blind loops were created without further manipulation; in the second the bile was diverted permanently into the lower ileum below the blind loop, whereas in a third neomycin was added to the drinking water throughout the experiment. Two weeks after the creation of the blind loops, they were used for structural and functional studies. 2. Morphometric and microdissection techniques demonstrated that the surface area of the individual villi of the mucosa of 'ordinary' blind loops had increased fourfold in comparison with corresponding control jejunum, whereas the increase was only twofold in rats with bile diversion or in the series treated with neomycin. There were proportional increases in crypt length and mitotoic activity of the crypts in all three series, which suggest that the alterations in the mucosa were due to hyperplasia in both villus and crypt compartments. 3. Sucrase, succinate dehydrogenase, alkaline phosphatase and non-specific esterase activities, determined biochemically or histochemically, were reduced in the mucosae of all blind loops, though the changes were most pronounced in the 'ordinary' blind loops. The accumulation of L-phenylalanine by mucosal slices in vitro was depressed, although the decrease was less marked in the series treated with neomycin. 4. These results suggest that both bacteria and deconjugated bile acids play a role in the development of the hyperplastic changes of the blind-loop mucosa, but that another factor might also be involved: as a possible candidate, stasis of the intestinal contents was considered. 5. To test this hypothesis, loops of rat colon were transposed into the jejunum. Above the transposed loop, the jejunal mucosa developed hyperplasia of both villus and crypt compartments, with a reduction in its ability to accumulate L-phenylalanine. It is argued that these changes, probably caused by stasis of the intestinal contents, are triggered off by the dilatation of the gut, which may also be implicated in the mucosal alterations in blind loops.

Alkaline Phosphatase↗

A kinetic study of the interactions between amino acids and monosaccharides at the intestinal brush-border membrane.

1. The influx of amino acids into guinea-pig intestinal rings in vitro is inhibited by monosaccharides, and that of monosaccharides by amino acids. Two hypotheses have been proposed to account for these heterologous interactions. According to the first, the cis hypothesis, there is an allosteric interaction between substrates binding to separate but related sites at the outer face of the brush-border membrane matrix. In contrast, the trans hypothesis envisages the interaction to result from a partial dissipation of the electrochemical sodium gradient due to the cotransport of each substrate with sodium ions. 2. In an attempt to distinguish between the merits of the two hypotheses, we examined the kinetics of the inhibition of phenylalanine influx by two sugars of widely different affinities, galactose and beta-methylglucoside. Since beta-methylglucoside carries more sodium into the cell than galactose, the trans hypothesis would predict it to be the stronger inhibitor, but in fact the opposite result is found. 3. Equations were developed to describe the inhibitions in accordance with the cis hypothesis. The satisfactory agreement between experimental observations and theoretical predictions provides support for the applicability of the model. Further implications of the polyfunctional carrier model are discussed.

Allosteric Regulation↗

Ischemic diseases of the large intestine.

The blood flow within the walls of the digestive tract must be sufficient to maintain its structural and functional integrity. All episodes of vascular insufficiency cause ischemic damage to the organ and carry the threat of diffuse or focal necrosis. Certain forms of ischemic colitis or proctitis arise from episodes of reduced peripheric or splanchnic blood flow; indeed, those that do not culminate in necorsis of the colonic wall are more frequently caused by hemodynamic disorders than by vascular occlusions. The crisis is often mitigated by the development of collateral circulation, which is nevertheless of rather meager quality, such that the patients are very vulnerable to subsequent slight changes in cardiac output. Necrotic, gangrenous ischemic colitis arises from a combination of occlusive damage to the arteries and general hemodynamic disturbances. The vascular insufficiency might be slight or severe, temporary or long-lasting, localized or diffuse. In addition, the attack occurs in a septic medium in the presence of an abundant microbial flora that may be highly pathogenic. Thus infection complicates and aggravates the ischemic damage, with the result that the gangrenous aspect of the lesions tends to hide their ischemic origin. Indeed, the variability of the manifestations of the disease represents one of its primary characteristics and is a function of the different causative factors. A knowledge of the anatomy and pathophysiology of the splanchnic circulation and its hemodynamics is essential for a full appreciation of the diagnosis and treatment of the disorders and for the adoption of the aggressive approach necessary to improve the poor prognosis of ischemic diseases of the colon and rectum. The salient points have been stressed in the present chapter. The features of the different forms of the disease have been described, together with the necessary medical treatment and the indications for surgical for surgical intervention. In the relatively rare cases where operation is necessary, the tactics and techniques have been described. All treatment should be based on (a) constant, prolonged intensive care; (b) precise monitoring of any change in status; and (c) rapid excision of any necrotic (often gangrenous) tissue. Ischemic colitis is most likely to occur in elderly patients with a history of cardiovascular disease, but it is not excluded in younger individuals. It is a frequent entity and is potentially lethal. Although its clinical, radiological, and anatomical characteristics permit its classification as a separate disease, it is often confused with other disorders of the colon. Although the abdominal surgeon is most likely to be concerned with this disease, the vascular surgeon who attacks the lower aorta should always be on the lookout for possible occurrences of segmentary ischemia of the distal colon as a result of his intervention.

Animals↗

[Blood flow disorders of the colon and rectum and their therapy].

Ischemic colitis or proctitis shows three evolutionary stages. a. complete recovery, b. fibrous stenosis, and c. acute ischemia leading to gangrene. The two first stages result more frequently from hemodynamic disorders than from vascular occlusions because, in the presence of the latter, collateral circulation develops. In addition, the colonic ischemia occurs in a septic medium in the presence of an abundant microbial flora which may be highly pathogenic.

Aged↗

Kinetics of the absorption of amino acids by the rat intestine in vivo.

The kinetics of L-phenylalanine and L-lysine absorption by the rat small intestine in vivo have been studied by perfusing intestinal segments and monitoring simultaneously the uptake of the substrate into the intestinal tissue and its disappearance from the perfusate. The rate of phenylalanine disappearance is a linear function of the substrate concentration. Its uptake into the tissue is rapid and obeys saturation kinetics, but is not concentrative. Both tissue uptake and disappearance rate can be inhibited by leucine or methionine, but are not influenced by hydrophilic neutral or dibasic amino acids. Lysine disappearance from the perfusate and its uptake into the tissue both display saturation kinetics. Lysine transport is quantitatively smaller than that of phenylalanine. Both uptake and disappearance are inhibited by arginine and leucine, but are unaffected by other neutral amino acids or sugars. To analyse the kinetic results, integrated equations were developed to express the final concentration in the perfusate in terms of the original concentration. The disappearance rate was considered as a mixed process (saturable and non-saturable in parallel) in a one-compartment system, and the uptake by the tissue was treated as a two-compartment system in which the amino acid entered the cells by a mixed process but left them by a pure non-saturable mechanism. The results concerning disappearance from the lumen are compatible with the one-compartment model. Phenylalanine absorption can be described by a major non-saturable component and a minor saturable one, while lysine absorption occurs almost entirely by a saturable process. The two-compartment model does not adequately describe the tissue uptake results.

Amino Acids↗