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Biomedical subjects

N B Roberts

Publications and source records attributed to N B Roberts.

At least 109 records · Page 6Linked to original sources
PubMed1980

Exogenous and endogenous acid and pepsins in the pathogenesis of duodenal ulcers in the rat.

A continuous subcutaneous infusion for 24 hr of the gastric secretagogues, pentagastrin (4 micrograms/kg/min) together with carbachol (0.8 micrograms/kg/min) produced a 100% incidence of duodenal ulcers (DU) in male albino Wistar rats. The mean acid output producing these duodenal ulcers was 2.3 mmol/24 hr, with a gastric secretory volume of 25 (+/- 1) ml/24 hr at an acid concentration of 91 (+/- 2) mmol/liter. The pepsin activity in the gastric juice was 185 micrograms/ml. To simulate this acid-pepsin hypersecretion, acid and/or pepsin was infused intragastrically for 24 hr. The intragastric infusion of hydrochloric acid (0.1 M, 0.2 M, 0.5 M) alone and hog purified pepsin (2.5, 5, 10 mg/24 hr) at a constant rate of 1 ml/hr for 24 hr failed to produce duodenal ulcers in rats although gastric lesions in the body of the stomach were produced. The infusion of 0.2 M HCl with 5 mg pepsin over 24 hr produced DU in two of 10 rats. However, pooled secretagogue-stimulated gastric juice, infused intragastrically, produced DUs in 11 of 12 rats. Acid alone does not produce DU experimentally in rats at the rate of infusion used in these experiments. Acid and exogenous procine pepsin (similar to human pepsin 3 on agar gel electrophoresis) rarely produced duodenal ulcers. However, acid and endogenous rat pepsin are needed together for the duodenal ulcerogenesis. This pepsin may be an obligatory ulcerogenic factor in the rat.

Animals↗
PubMed1980

The actions of carbenoxolone on enzymes and their relation to its therapeutic effect.

Carbenoxolone may bind to enzymes, inhibiting or activating them. Enzymes inhibited are human pepsins 1, 3 and 5, human pepsinogens 1, 3 and 5, swine pepsin, bovine trypsin, bovine chymotrypsin, porcine elastase, human gastric proteinase 2, human gastric prostaglandin 15-OH dehydrogenase and delta-5 reductase, and pronase. Enzymes activated are papain, bovine carboxypeptidase and gastric microsomal glycosyl transferase. Enzymes unaffected are human pancreatic amylase and porcine pancreatic lipase. Binding occurs away from the active site; inhibition thus occurs when binding impedes access of substrate to, or products from, the active site, and activation when access is facilitated. Carbenoxolone causes increased secretion of mucus; this action can be explained by activation of the gastric glycosyl transferases. Carbenoxolone also causes intraluminal loss of peptic activity and diminished secretion of pepsins; these actions are explained respectively by intraluminal inhibition of the pepsins and intramucosal inactivation of the pepsinogens, particularly of the peptic ulcer-associated enzyme, pepsin 1. The healing effect of carbenoxolone in peptic ulcer involves these actions together with a reduced turnover of gastric mucosal cells. Pepsins 1 and 3 have collagenolytic activity, causing release of alpha-chains from native collagens. Pepsin 1 is five-fold the more active. Carbenoxolone inhibits peptic collagenolysis.

Animals↗
PubMed1979

Action of human pepsins 1,2,3 and 5 on the oxidized B-chain of insulin.

Human pepsins 1 and 2 attack the B-chain of oxidized insulin at pH 1.7 at the same bonds as does human pepsin 3. At pH 3.5, pepsins 1 and 2 attack insulin B-chain at essentially the same bonds as at pH 1.7, but more slowly. For all three enzymes, the first bond to be hydrolysed is Phe(25)-Tyr(26), followed simultaneously by Glu(13)-Ala(14), Leu(15)-Tyr(16) and Tyr(16)-Leu(17). Human pepsin 5, however, attacks Phe(24)-Phe(25) first of all, followed by Leu(15)-Tyr(16) and Tyr(16)-Leu(17). The results suggest that each pepsin has only one active site. Acid hydrolysis indicates that the sites of enzymic cleavage are not bonds with an inherent instability at low pH.

Amino Acid Sequence↗
PubMed1979

Hereditary aspects of duodenal ulceration: pepsin 1 secretion in relation to ABO blood groups and ABH secretor status.

Pepsin 1, the ulcer-associated pepsin, occurred significantly more frequently in the gastric juice of those patients with duodenal ulcer who did not secrete A, B, or H antigens into gastric juice than in those secreting these antigens. This observation may explain the increased proportion of such non-secretors among patients with duodenal ulceration. In patients with gastric ulcer and non-ulcer dyspepsia, and in a miscellaneous group of patients, there was no association of pepsin 1 secretion with secretor status, suggesting that the association noted in duodenal ulceration is an indirect rather than a direct one. No increase of pepsin 1 occurred in group O patients with peptic ulcer, so that the increased proportion of such patients in peptic ulcer does not arise from differences in pepsin 1 secretion.

ABO Blood-Group System↗
PubMed1978

The preparation and purification of individual human pepsins by using diethylaminoethyl-cellulose.

A procedure was devised for isolating human pepsins 1, 2, 3 and 5 from gastric juice by repetitive column chromatography on DEAE-cellulose. The combined yields in four different experiments varied from 14% to 90% of the total peptic activity of the starting material. The isolated individual pepsins were shown to behave as single homogeneous proteins on agar-gel electrophoresis at pH 5.0 and on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. There is preliminary evidence, requiring further study, of two other pepsins, one migrating between pepsins 1 and 2 and the other a pepsin-3 component associating closely with pepsin 5 on chromatography.

Chromatography, DEAE-Cellulose↗
PubMed1978

The isolation and properties of a non-pepsin proteinase from human gastric mucosa.

1. A non-pepsin proteinase, proteinase 2, was successfully isolated free from pepsinogen (by repetitive chromatography on DEAE- and CM-celluloses) from the gastric mucosa of a patient with a duodenal ulcer and the uninvaded mucosa of a patient with a gastric adenocarcinoma. 2. Proteinases 1a and 1b, found in gastric adenocarcinoma, were not found in the gastic mucosa of these patients. 3. Proteinase 2 was shown to have an asymmetrical broad pH-activity curve with a maximum over the pH range 3.0-3.7. 4. Proteolytic activity of proteinase 2 was inhibited by pepstatin; the concentration of pepstatin giving 50% inhibition is of the order of 3nm. 5. Inhibition of proteolytic activity by carbenoxolone and related triterpenoids indicated that at pH 4.0 proteinase 2 possesses structural characteristics relating it to the pepsins and at pH 7.4 to the pepsinogens. 6. The sites of cleavage of the B-chain of oxidized insulin for proteinase 2 at pH 1.7 and pH 3.5 were shown to be similar to those previously established for human pepsin 3 and for the cathepsin E of rabbit bone marrow. 7. The non-pepsin proteinase 2 (cathepsin) of human gastric mucosa has properties more similar to cathepsin E than to the cathepsins D.

Binding Sites↗
PubMed1978

Effect of cyclo-alkyl lactamimides upon human pepsins and pepsinogens.

1. Eight cyclo-alkyl lactamimides have been investigated for potential inhibitory action upon the pepsins and pepsinogens. 2. Human pepsins 1, 3 and 5 and swine pepsin were inhibited only slightly. 2. Human and swine pepsinogens were inactivated progressively by lactamimides as the number of methylene groups in the nitrogen-containing ring increased. The most potent inactivator studied was N-(cis-2-phenylcyclopentyl)-azacyclotridecan-2-imine hydrochloride. 4. Substitution of benzyl and tertiary butyl groups in the N-containing ring increased the pepsinogen-inactivating property of the cyclo-alkyl lactamimides. 5. N-(cis-2-Phenylcyclopentyl)azacyclotridecan-2-imine hydrochloride may be of potential importance as a therapeutic agent in peptic ulcer, and modifications to the molecule which might increase its pepsinogen-inactivating ability are suggested.

Humans↗
PubMed1978

An improved automated method for the analysis of inorganic phosphate without dialysis.

A procedure is described for automating the analysis of inorganic phosphate in physiological media without dialysis. Sodium dodecyl sulphate is used to maintain protein solubility during the analysis. Sample analysis was measured at 60 and 90 samples an hour. The inorganic phosphate results obtained for a series of human plasma and for various internal control sera by non-dialysis and dialysis showed good agreement.

Autoanalysis↗
PubMed1978

Alternative mechanized method for analysis for inorganic phosphate without reduction.

The mechanized measurement of inorganic phosphate in plasma can be achieved without reduction by only minor alterations to an existing continuous-flow reduction procedure. The method is based on the enhancement of the extinction of the phosphomolybdate complex by the detergent Triton X-100. Results obtained agree well with those obtained by the standard reduction (Fiske-SubbaRow) procedure. The correlation coefficient between the two methods was 0.996 and statistical analysis of the data confirmed very good agreement between the two sets of values.

Autoanalysis↗
PubMedDate not supplied

Activation of L-arginine transport in undialysed chronic renal failure and continuous ambulatory peritoneal dialysis patients.

1. Treatment with haemodialysis and continuous ambulatory peritoneal dialysis (CAPD) presents different pathophysiological profiles and it has been suggested that clinical outcome in chronic renal failure may depend on the mode of dialysis. The transport of L-arginine, a precursor of nitric oxide, into blood cells is increased in uraemic patients on haemodialysis. The present study was designed to investigate L-arginine transport into red blood cells (RBC) in uraemic patients not yet on dialysis and on CAPD therapy. 2. Eleven uraemic patients not yet on dialysis and 17 on CAPD were included in the study. L-Arginine transport into RBC and plasma and RBC amino acid profiles were analysed in these sets of patients. 3. L-Arginine transport via system y(+), but not y(+)L, into RBC, was significantly increased in undialysed uraemic patients (459 +/- 40 micromol/L per cell per h) and CAPD patients (539 +/- 61 micromol/L per cell per h) compared with controls (251 +/- 39 micromol/L per cell per h). High-pressure liquid chromatography measurements demonstrated low levels of plasma L-arginine in uraemic patients both on CAPD (54 +/- 3 micromol/L) and not yet on dialysis (80 +/- 6 micromol/L) compared with control subjects (146 +/- 14 micromol/L). 4. Our findings provide the first evidence that uraemic patients not yet on dialysis and on CAPD present with an activation of L-arginine transport via system y(+) into RBC associated with reduced plasma levels of L-arginine.

Arginine↗
PubMedDate not supplied

Hypermanganesemia in long-term intravenous nutrition and chronic liver disease.

BACKGROUND: Hypermanganesemia and cholestatic liver disease are both recognized complications of long-term IV nutrition. Manganese is primarily excreted in bile, and recent studies have indicated that manganese toxicity may play a role in the pathogenesis of IV nutrition-associated cholestasis. METHODS: Whole blood and plasma manganese concentrations were measured in patients receiving long-term home IV nutrition (HIN, n = 30). Whole blood manganese concentrations also were measured in patients with chronic liver disease (CLD, n = 10) and control subjects (n = 10). RESULTS: Whole blood manganese concentrations of all CLD patients were within the reference interval (73 to 210 nmol/L) and were not different from those of the control group (151 +/- 44 nmol/L, CLD vs 155 +/- 35 nmol/L, control; not significant), despite the presence of cholestasis. In contrast, whole blood manganese concentration was increased (>210 nmol/L) in 26 patients, and plasma manganese concentration increased (>23 nmol/L) in 23 of the patients receiving HIN. None of the patients exhibited neurologic signs of manganese toxicity. There was no correlation between whole blood manganese concentrations and markers of cholestasis, IV manganese intake, or duration of HIN. However, plasma manganese concentration correlated both with average weekly IV manganese intake (r = .44, p = .02) and with gamma-glutamyl transferase (r = .43, p = .02) and alkaline phosphatase activities (r = .55, p = .003). CONCLUSIONS: Cholestatic liver disease does not appear to contribute to increased whole blood manganese concentrations in patients not receiving HIN. Plasma manganese concentrations in patients receiving HIN reflect recent manganese exposure and impaired excretion where cholestasis is present. The lack of relationship between plasma and whole blood manganese concentrations suggests that factors other than manganese intake and excretion affect intracellular concentrations.

Adult↗