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Biomedical subjects

J T Harries

Publications and source records attributed to J T Harries.

At least 37 records · Page 2Linked to original sources

Characteristics of intact lactose transport in rat jejunum in vitro.

The characteristics and kinetics of intact transmucosal transport of lactose have been studied in the rat jejunum using an everted sac preparation. Lactose transport displayed linear kinetics up to the maximum concentration (150 mM) of lactose studied. Ouabain (1 mM) when placed in the serosal solution, and phlorhizin (0.1 mM) when placed in the mucosal solution, had no significant effect on lactose transport. In contrast to glucose, transport of intact lactose did not occur against a concentration gradient. These results strongly suggest that intact transmucosal transport of lactose occurs by a process of simple passive diffusion, and that it is independent of the sodium-coupled glucose transport system.

Animals↗

Loperamide modifies Escherichia coli, heat-stable enterotoxin-induced intestinal secretion.

We have shown previously that loperamide, an opiate analogue, inhibits cholera-toxin- and prostaglandin E2-induced secretion in the rat small intestine. In these studies loperamide modified secretion induced by partially purified Escherichia coli, heat-stable enterotoxin in infant mice. The drug was effective whether administered before or after established secretion. These experiments provide further suggestive evidence that loperamide has a broad spectrum of antisecretory activity.

Animals↗

Fat absorption in the newborn.

Dietary fat is an important source of energy to the newborn. Pancreatic lipase and esterase activity are both low in newborns, particularly in premature ones; similarly, bile salt metabolism is markedly compromised. This could result in grossly defective intraluminal lipolysis and micellar solubilisation, leading to appreciable steatorrhea and energy loss. Lingual lipase and bile salt-stimulated lipase (BS-SL), however, play an important compensatory role. Lingual lipase is secreted from branching serous glands (von Ebner's glands) located on the dorsal aspect of the posterior region of the tongue, and its physicochemical properties are highly suited to passage through the stomach into the small intestine; a high fat diet and the act of suckling stimulates this enzyme's activity, and it may act in a synergistic fashion with pancreatic lipase. BS-SL (i.e. milk lipase) also has properties which are well designed for promoting fat absorption in the newborn. For example, it has no positional specificity for the ester bonds of the triglyceride molecule, and the optimal concentration of bile salts required for activation are low.

Absorption↗

The effect of cimetidine on meal-stimulated gastric function and exogenous pancreatic enzymes in cystic fibrosis.

Some patients with cystic fibrosis (CF) have malabsorption of fat and protein in spite of large amounts of supplemental pancreatic enzymes. This is partly due to acid inactivation of exogenous pancreatic enzymes in the stomach. The effect of cimetidine on gastric function and exogenous pancreatic enzymes was assessed by a marker perfusion technique in 4 CF children in a double-blind controlled fashion. Gastric acid secretion was higher in CF patients than in controls (P less than 0.005) and was reduced significantly by oral cimetidine (P less than 0.02). Rapid inactivation of exogenous trypsin and lipase occurred when gastric pH fell to less than 4.5. There was no loss of enzyme activity during treatment with cimetidine when gastric pH remained above 5.5. Activity of lipase and trypsin in the jejunum improved in all subjects. Fat and nitrogen absorption assessed by a balance technique during the study period showed a small improvement in fat absorption while on cimetidine. We conclude that some CF patients have a high meal-stimulated gastric acid output which causes inactivation of trypsin and lipase. Cimetidine was effective in reducing acid secretion in such patients and led to small improvements in fat absorption.

Adolescent↗

Total colonoscopy in children.

One hundred and twenty-three total colonoscopies were performed on 115 children with ages ranging from 3 months to 16 years. The major indications were suspected inflammatory bowel disease and unexplained rectal bleeding. Ninety-seven per cent of all procedures were carried out with sedation only. Adult colonoscopes were used in most of the patients but in babies and small children paediatric instruments were preferable. Total colonoscopy was possible in all patients with a patent colon. The terminal ileum was examined in 63 patients. Endoscopic snare polypectomy was successfully carried out in 8 children and multiple haemangiomas were electrocoagulated in one. Total colonoscopy in this paediatric series proved to be at least as easy, rapid, well-tolerated, and safe as in adults. In selected patients as single colonoscopy can give an accurate diagnosis with biopsy proof and sometimes the opportunity for definitive treatment.

Adolescent↗

Loperamide: studies on its mechanism of action.

The effects of loperamide on net solute and water absorption, and prostaglandin E2 (PGE2) and cholera toxin-induced secretion were studied in the rat jejunum using an in vivo steady-state perfusion technique. Loperamide stimulated absorption of fluid, electrolytes, and glucose and reversed PGE2 and cholera toxin-induced secretion to absorption; this opiate analogue had no effect on cholera toxin stimulation of adenylate cyclase activity or the rise of tissue cyclic AMP (cAMP) concentrations. The opiate antagonist, naloxone, reduced the antisecretory effects of loperamide without affecting tissue levels of cAMP. These results indicate that loperamide inhibits PGE2 and cholera toxin-induced secretion, and that this phenomenon is independent of any direct effect that cholera toxin has on the adenylate cyclase system. The action of naloxone suggests, but does not prove, that loperamide exerts its effect via opiate receptors.

Adenylyl Cyclases↗

A family study of protracted diarrhoea in infancy.

A family study of undiagnosed protracted diarrhoea in infancy was undertaken, based on 67 such patients, seen at The Hospital for Sick Children, London, over a 6-year period. All were fully investigated with the exclusion of those with known cause, such as coeliac disease, cow's milk intolerance, or enteric infections. The families were traced and visited. The material is certainly heterogeneous. In the case of five patients the condition was associated with a syndrome. The remaining 62 index patients could be divided into a group of 15 with severe illness and 47 with a milder illness. Six had onset before one month of age, four died, and in five the diarrhoea lasted more than 12 months and the children persistently failed to thrive. These 15 severe cases had six affected sibs out of 22 (Weinberg proband method) and in all but one of these affected sibs the condition was also severe. Two further sibs had had protracted diarrhoea, but this had not been fully investigated. The 47 index patients with milder disease had 68 sibs of whom only one was affected (this boy was one of the severely affected index patients), and one other sib had protracted diarrhoea which was not fully investigated. It is proposed that the severe group includes one or more autosomal recessive entities, in which the basic defects are not yet known, but are likely to be inborn metabolic errors.

Birth Weight↗

Cystic fibrosis "factor(s)": present also in sera of Schwachman's pancreatic insufficiency.

Using an in vivo closed-loop technique in rat jejunum, we have confirmed previous in vitro studies that cystic fibrosis (CF) serum inhibits water, sodium, and glucose absorption and transmural potential difference. CF heterozygote serum or sera form children with diarrhoeal disorders not associated with exocrine pancreatic insufficiency had no effect of transport. Sera from patients with Shwachman's syndrome and exocrine pancreatic insufficiency had identical effects to CF serum. These results challenge the specificity of the CF "factor."

Body Water↗

Optimization and validation of assays to estimate pancreatic esterase activity using well-characterized micellar solutions of cholesteryl oleate and tocopheryl acetate.

Studies have been carried out to determine the maximal solubilization of cholesteryl oleate and tocopheryl acetate within mixed bile salt-fatty acid micelles and to establish reproducible assays for pancreatic esterase activity using these micellar substrates. At pH 8.5, using 30 mM sodium taurocholate and 10 mM oleic acid, reproducible micellar solutions of the esters could be prepared giving micellar concentrations of 0.4 mM and 0.1 mM for tocopheryl acetate and cholesteryl oleate, respectively. Conditions were then optimized to estimate pancreatic esterase activity using these micellar-solubilized substrates. Maximal activity was obtained at pH 8.5 with 2-4 mM oleic acid and 15-30 mM sodium taurocholate, and gave coefficients of variation for the assays of 7.4% and 20.2% using tocopheryl acetate and cholesteryl oleate, respectively, as substrates. Micellar-solubilized cholesteryl oleate and tocopheryl acetate, together with a non-micellar system using p-nitrophenyl acetate, were used to estimate esterase activity in human duodenal aspirates and rat pancreatic homogenates. Esterase activity in children with cystic fibrosis was greatly reduced and paralleled tryptic and pancreatic lipase activity, which suggested that the esterase activity was pancreatic in origin. The results of this study, therefore, provide a basis for future investigations concerned with the hydrolysis and absorption of dietary esters.

Animals↗

Studies on the in vivo absorption of micellar solutions of tocopherol and tocopheryl acetate in the rat: demonstration and partial characterization of a mucosal esterase localized to the endoplasmic reticulum of the enterocyte.

The in vivo absorption of alpha-tocopherol from micellar solubilized solutions of free alpha-tocopherol and alpha-tocopheryl acetate was investigated using isolated loops of rat jejunum and found to be similar. Although analysis of the fluid remaining in the loop following the absorptive period with tocopheryl acetate showed that esterase activity and free tocopherol were present, calculations suggested that luminal hydrolysis of the ester could not have accounted for the similar rates of absorption of the free and esterified tocopherols. A mucosal source of the esterase activity was postulated and subsequently identified and characterized with respect to pH optimum, enzyme kinetics, and activation by bile salts, and shown to be distinct from pancreatic esterase. Analytical subcellular fractionation studies on homogenates of isolated jejunal enterocytes demonstrated that esterase activity against both p-nitrophenyl acetate and tocopheryl acetate was localized to the endoplasmic reticulum. These studies suggest that although the bulk of tocopheryl esters are normally hydrolyzed in the intestinal lumen by pancreatic esterase prior to uptake, some of the esters may be hydrolyzed intraluminally by the mucosal enzyme and some taken up intact by the jejunal mucosa and hydrolyzed intracellularly. This mucosal esterase may be of particular importance in conditions of pancreatic insufficiency.

Acetylesterase↗

Short stature as the primary manifestation of coeliac disease.

Thirty-four patients with short stature of undetermined cause and no gastrointestinal symptoms underwent jejunal biopsy for exclusion of coeliac disease. Eight had subtotal or severe partial villous atrophy and seven showed a significant acceleration in height and weight velocity after the introduction of a gluten-free diet. Short stature by itself, in the complete absence of gastrointestinal symptoms, is an indication for jejunal biopsy, particularly if bone age is delayed by more than 4 years and/or there are associated haematological abnormalities.

Adolescent↗