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Biomedical subjects

J Kelleher

Publications and source records attributed to J Kelleher.

At least 37 records · Page 2Linked to original sources

Intestinal absorption of the intact peptide carnosine in man, and comparison with intestinal permeability to lactulose.

1. Healthy humans ingested the dipeptide carnosine (L-beta-alanyl-L-histidine). Their plasma levels and urinary outputs of carnosine and beta-alanine were monitored over the following 5 h. 2. Large amounts of intact carnosine (up to 14% of the ingested dose) were recovered in the urine over the 5 h after ingestion. However, carnosine was undetectable in the plasma unless precautions were taken to inhibit blood carnosinase activity ex vivo during and after blood collection. 3. The amount of carnosine recovered in urine varied substantially between subjects. It correlated negatively with carnosinase enzymic activity in the plasma. Highest carnosinase activities were observed in those subjects who regularly underwent physical training. 4. Urinary recovery of the disaccharide lactulose also varied considerably between subjects, but was substantially lower than that of carnosine. There was no significant correlation between the recoveries of carnosine and lactulose. 5. When lactulose was ingested with a hypertonic solution, the urinary recovery of lactulose was generally increased. When carnosine was ingested with a hypertonic solution, the urinary recovery of carnosine was reduced: hence the paracellular route probably is not dominant for absorption of intact carnosine. 6. Intact carnosine must have crossed the intestine to an extent much greater than hitherto recognized. Rapid post-absorptive hydrolysis is a severe obstacle to quantification of intact peptide absorption.

Adult↗

Alcohol consumption in patients with colorectal adenomatous polyps.

The risk of developing colorectal adenomatous polyps is probably increased by a variety of dietary and environmental factors. We found an association with current alcohol and cigarette consumption. The risk of polyps was increased three times in drinkers who did not smoke and two times in smokers who did not drink, with those who both drank and smoked having 12 times the risk of total abstainers. Since colonic adenomatous polyps are generally regarded as premalignant lesions, these results lend support to the view that alcohol consumption may be an important factor in the pathogenesis of colorectal neoplasia, thus reinforcing the proposed polyp/carcinoma sequence in colorectal carcinogenesis. The role of smoking, however, is less clear particularly since the lack of association of colorectal carcinoma and smoking has been reported in many other studies.

Aged↗

Effect of fasting, self-selected and isocaloric glucose and fat meals and intravenous feeding on plasma zinc concentrations.

This study investigated the effect of fasting, self-selected meals and isocaloric oral glucose and fat meals and intravenous (i.v.) feeding on plasma zinc concentrations in men. Plasma zinc remained stable when volunteers fasted all day, but self-selected meals and 600 kCal of dextrose or fat emulsion caused significantly reduced plasma zinc concentrations [mean (SD) 12.1 (1.4), 12.3 (0.6) and 12.2 (0.7) mumol/L at 1400 h, respectively, compared with a fasting level of 13.9 (1.6) mumol/L at 0800 h, P less than 0.05]. In patients undergoing intravenous hyperalimentation, plasma zinc decreased from 12.0 (1.4) mumol/L at 0800 h to 10.0 (1.1) mumol/L at 1400 h [mean (SD), P less than 0.01]. These data show that both enteral and i.v. feeding cause a decline in plasma zinc and that glucose alone is not responsible for this post-prandial fall since ingestion of isocaloric amounts of glucose or fat have a similar effect.

Circadian Rhythm↗

HIV testing.

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Communication↗

Pancreatic exocrine function after a sutureless pancreatico-jejunostomy following pancreaticoduodenectomy.

Exocrine pancreatic function was measured in 14 patients after pancreaticoduodenectomy for periampullary neoplasms in order to assess the patency of a sutureless pancreatico-enteric anastomosis. Pancreatic function was examined by the p-aminobenzoic acid/p-aminosalicylic acid (PABA/PAS) test 3-160 months after operation and compared with age- and sex-matched controls. There were no significant differences between mean (s.e.m.) serum PABA concentrations 3 h after ingestion of N-benzoyl-L-tyrosyl-PABA (25.5 (3.6)) mumol/l for patients, 26.1 (2.0) mumol/l for controls). However, the mean (s.e.m.) PABA excretion index was significantly lower in the patients (0.58 (0.08)) than in the controls (0.76 (0.04)). Four patients required pancreatic enzyme supplements for control of diarrhoea. Self-limiting pancreatic leaks occurred in two patients. The results suggests that the sutureless pancreatico-enteric anastomosis has an acceptably low leakage rate but that pancreatic exocrine function is diminished following pancreaticoduodenectomy with this technique. However, the majority of patients require no enzyme supplements and no significant tendency to late stenosis of the anastomosis was demonstrated.

4-Aminobenzoic Acid↗

Interactions of retinoic acid and androgens in human prostatic tissue.

The effect of retinoic acid (RA) on testosterone metabolic pathway was investigated in hyperplastic and neoplastic human prostatic tissues, and also the effects of steroids on RA binding to its receptor. Steroids only had a minimal effect on the binding of RA by its receptor. The conversion of testosterone to DHT by 5 alpha-reductase was reduced in the presence of retinoic acid. The inhibition was probably due to competition with NADPH for enzyme binding sites. The degree of inhibition found with retinoic acid at a concentration of 10(-4)M was greater for hyperplastic (41%) than that for neoplastic tissue (24%). The inhibition of 5 alpha-reductase by retinoic acid was dose-dependent. The activity of 5 alpha-reductase is significantly less in neoplastic compared with hyperplastic tissue.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

The effect of zinc and vitamin C supplementation on the immune status of patients with Crohn's disease.

The immune status of 29 patients with Crohn's disease given oral supplements of Vitamin C, zinc or placebo for three-week periods was studied. Collectively, the patients showed T-cell hyporesponsiveness, as assessed by phytohaemagglutinin stimulation, which was significantly improved by Vitamin C. Both monocyte function, as assessed by latex phagocytosis, and pan T-Cell number were significantly reduced and were not influenced by supplementation. Humoral immunity, assessed by pokeweed mitogen-induced immunoglobulin synthesis, was normal and remained unchanged. Vitamin C supplements improved T-cell function in Crohn's disease, whereas neither Vitamin C nor zinc had a measurable effect on humoral immunity.

Journal Article↗

Cellular and muscle zinc in surgical patients with and without gastrointestinal cancer.

1. The zinc status of surgical patients with and without gastrointestinal cancer was studied. 2. Plasma zinc was lowest in patients with cancer concurrent with depressed plasma albumin concentrations. 3. Polymorphonuclear cell zinc was decreased in both patient groups and correlated strongly with abdominal muscle zinc (r = 0.89, P less than 0.001). 4. Mononuclear cell and total leucocyte zinc were similar to control values in both groups of patients. Total leucocyte, but not mononuclear cell, zinc correlated weakly with muscle zinc (r = 0.48, P less than 0.05). 5. The results suggest that polymorphonuclear cell zinc may be better than leucocyte zinc in assessing zinc status and that some surgical patients may be zinc-depleted. The presence of gastrointestinal cancer did not influence the zinc status.

Adult↗

Clinical monitoring of steatorrhoea in cystic fibrosis.

In 100 patients with cystic fibrosis the severity of steatorrhoea was assessed by three separate methods. Using chemical faecal fat assay as the gold standard, two other rapid and inexpensive methods were compared with it. The steatocrit method proved unreliable in our hands and gave little indication of the presence or severity of steatorrhoea. The more simple microscopy method was highly sensitive (97%) and only three of 80 patients with steatorrhoea were missed. All patients with severe steatorrhoea (greater than 60 mmol fat/day) were clearly demonstrated. The method is applicable to spot faecal samples and can readily be carried out on an outpatient basis. In centres where faecal fat assays are not available, the simple and cheap microscopic examination will give some indication of the response to enzyme treatment and may also help to identify non-compliant individuals.

Adolescent↗

Relation between zinc status and hepatic functional reserve in patients with liver disease.

Patients with liver disease may be at risk of zinc depletion. We measured polymorphonuclear cell, mononuclear cell, plasma, and erythrocyte zinc values, and erythrocyte carbonic anhydrase activity to assess zinc status in 17 patients with non-alcoholic liver disease (primary biliary cirrhosis and chronic active hepatitis) and 13 patients with alcoholic liver disease. The plasma zinc concentration was reduced in both patient groups and correlated strongly with the plasma albumin concentration. The mean polymorphonuclear cell zinc value in both groups was similar to that of controls but when results were combined and grouped according to hepatic functional reserve, patients with more severe liver damage (grade C) had a lower polymorphonuclear cell zinc value (mean (SD) 0.86 (0.24) nmol/mg protein) than patients with grade A (1.44 (0.43) nmol/mg protein, p less than 0.01) or grade B liver damage (1.08 (0.30) nmol/mg protein, p less than 0.05), or control subjects (1.26 (0.28) nmol/mg protein, p less than 0.001). The polymorphonuclear cell zinc value did not correlate with other indices of zinc status. The mononuclear cell zinc value was normal in all patients and was unrelated to hepatic damage. The erythrocyte zinc value and carbonic anhydrase activity were raised in alcoholic patients only. Since the polymorphonuclear cell zinc concentration is low in human experimental zinc deficiency and also correlates with tissue zinc, we suggest that our results provide evidence of progressive leucocyte zinc depletion in patients with liver disease.

Adult↗

Effects of linoleic acid and mitogenic stimulation on the fatty acid composition of human lymphocytes.

Perturbation of the fatty acid composition of human lymphocytes in vitro was investigated by addition of linoleic acid complexed to bovine serum albumin (BSA-LA) and by mitogenic stimulation with phytohaemagglutinin (PHA). BSA-LA resulted in a 45% increase in linoleic acid in phosphatidylethanolamine (PE) and over 100% in phosphatidylcholine (PC) in peripheral blood cells. Supplementation with BSA-LA in PHA-stimulated lymphocytes produced even greater changes: 100% increase in linoleic acid content for PE and over 300% for PC. There was a large decrease in oleic acid: 40% for PE and almost 100% in PC. Significant decreases in arachidonic acid occurred in both phospholipid fractions. PHA alone also altered membrane phospholipid fatty acid composition, with reductions in palmitic, stearic and linoleic acid for PE and increases in oleic acid and arachidonic acid (almost 100%). For PC, there were large decreases in stearic (40%), linoleic (30%) and arachidonic (40%) acids, together with an increase in oleic acid (65%). Cells supplemented with linoleic acid grown in the presence of PHA, compared with those grown in linoleic acid-supplemented medium alone, showed a 40% decrease in palmitic acid and a 55% increase in arachidonic acid in PE. For PC, there were large decreases in stearic acid (40%) and arachidonic acid (57%). Antibody-induced redistribution of surface molecules ('capping') was inhibited by some 14% after incubation with BSA-LA. However, no consistent alterations in PHA-induced cell proliferation were observed. These data suggest that profound alterations of membrane fatty acid composition occur spontaneously during the mitotic cycle, and may be further induced by experimental manipulation, without gross perturbation of cell function.

Arachidonic Acid↗

Ascorbic acid: a factor concentrated in human gastric juice.

1. Concentrations of ascorbic acid (ascorbic and dehydro-ascorbic; A + D; measured by the 2,4-dinitrophenylhydrazine method) of nearly three times those of plasma are present in gastric juice samples from patients with normal gastric histology. 2. A significant reduction in gastric juice ascorbic acid (A + D) was observed in patients with chronic gastritis. This reduction in concentration was independent of the grade of gastritis. 3. Concentrations of ascorbic acid (A + D) in gastric biopsy specimens were consistently higher in the antrum than in the body of the stomach. 4. These data demonstrate that considerable quantities of ascorbic acid (A + D) are normally 'secreted' into the stomach. 5. Ascorbic acid (ascorbic only; A; measured by h.p.l.c.) was present predominantly in its biologically active form in the patients with normal gastric histology. However, in patients with gastritis, independent of grade, ascorbic acid was present predominantly in its oxidized, biologically inactive form.

Adult↗

Preparation and characterization of a [14C]cellulose suitable for human metabolic studies.

In six normal subjects administered 5 microCi of an oral dose of a commercially available 14C-labelled cellulose, significant amounts of 14CO2 were detected in expired air within 30 min, suggesting that other 14C-labelled non-cellulosic material was present. Chemical and microscopical examination confirmed that starch was the principal contaminant. The commercial preparation was purified using amyloglucosidase (EC 3.2.1.3) digestion following gelatinization of the starch by autoclaving. Subsequent administration of the purified cellulose to a further six normal subjects decreased the expired air 14CO2 during the subsequent 10 h from 13.0 (SD 4.0) to 4.1 (SD 1.9)%. Administration of the purified product to a further group of four normal subjects, before and after a regimen of increased dietary fibre, showed a cumulative increase in expired 14CO2 over 24 h from 7.9 (SD 1.1) to 12.1 (SD 2.6)% on fibre. In six ileostomy subjects the cumulative excretion of 14CO2 was greatly decreased compared with normal controls (3.0 (SD 1.14) and 10.5 (SD 3.9)% respectively). In constipated subjects expired 14CO2 continued beyond 48 h, in contrast to normal subjects where expired 14CO2 at this time was negligible.

Adult↗

Zinc concentrations in pure populations of peripheral blood neutrophils, lymphocytes and monocytes.

It is doubtful if the measurement of plasma or serum zinc is of value in assessing zinc status. Leucocyte zinc has been suggested as an alternative since it may be representative of tissue zinc stores; but in many studies poorly defined cell populations make interpretation difficult. This paper describes detailed techniques for the isolation and analysis of pure populations of neutrophils, lymphocytes and monocytes. Zinc concentrations (+/- 1SD) in normal subjects were 1.26 +/- 0.27 nmol/mg protein, 1.85 +/- 0.32 nmol/mg protein and 2.58 +/- 0.65 nmol/mg protein in neutrophils, lymphocytes and monocytes respectively. Fasting caused a significant decrease in neutrophil and lymphocyte zinc, and an increase in monocyte zinc. Supplementation of zinc-replete subjects with 135 mg zinc/day for 3 weeks had no significant effect on cellular zinc concentrations.

Cell Separation↗