Search PubMed⌕ Search

Biomedical subjects

V Walker

Publications and source records attributed to V Walker.

At least 91 records · Page 5Linked to original sources

Production of prostaglandins and thromboxane by isolated cells from intracranial tumours.

Tumour cell-rich platelet-free preparations were isolated from 21 fresh samples of human intracranial tumours using enzymic digestion, followed by discontinuous density gradient centrifugation on Percoll and (14 preparations) adherence on plastic. Of the disaggregated cells 79.8 to 97.7% (mean 86.2%) were tumour cells, and mean cell viability was 82.6%. All the tumours produced prostaglandin (PG), E2, F2 alpha, 6 oxo F1 alpha and Thromboxane B2 during 16 hours of incubation but the amount varied widely. Highest production of PGE2 and TXB2 per 10(5) cells was by the eight meningiomas in which the prostanoid profile closely resembled that of circulating monocytes.

6-Ketoprostaglandin F1 alpha↗

Arterial eicosanoid production following chronic exposure to a periarterial haematoma.

Cisternal and lumbar cerebrospinal fluid obtained some days following a subarachnoid haemorrhage contains abnormally large quantities of various prostanoids; some may be partly the result of abnormal production by the cerebral arteries. The extra-arterial and intra-arterial production of 6 oxo PGF1 alpha (prostacyclin metabolite), PGE2, PGF2 alpha and TXB2 were measured in perfused rabbit common carotid arteries taken both from normal rabbits and from rabbits in which the arteries had been ensheathed by blood clot in vivo for 7 days using two techniques. Prostaglandin production by control arteries was highest during the first hour of perfusion but declined or increased marginally (PGE2) during the succeeding three hours. Arteries exposed to a periarterial haematoma for 7 days produced prostaglandins at a high rate throughout the 4 hours of study, and there was a progressive and marked increase in PGE2 production. The disproportionate increase in the cerebral vasoconstrictor PGE2 may reflect the inflammatory response which occurred in the adventitia of the vessels. Increased prostanoid production by cerebral arteries probably does contribute to the increased levels in CSF after subarachnoid haemorrhage.

6-Ketoprostaglandin F1 alpha↗

Urinary screening for abnormalities of amino acid or mucopolysaccharide metabolism in patients in a hospital for the mentally handicapped in Wessex.

Urine from 348 patients of a hospital for the mentally handicapped in Wessex was screened for abnormalities of aminoacid and mucopolysaccharide excretion. Persistent aminoacid abnormalities were found in 16 patients: two had phenylketonuria and one a severe variant form of hyperphenylalaninaemia (dihydropteridine reductase deficiency). In at least nine of the other patients, the observed abnormality was probably a secondary phenomenon. Two patients excreted excessive amounts of a glycosaminoglycan identified tentatively as hyaluronic acid. The study also uncovered one undiagnosed diabetic and three patients with urinary tract infection.

Adult↗

Effects of subarachnoid haemorrhage on intracranial prostaglandins.

Prostaglandins E2, F2 alpha, 6 oxo F1 alpha and thromboxane B2 increased in cisternal CSF following mock subarachnoid haemorrhage in dogs, particularly PGE2 (X25.5). Concentrations were increased also in lumbar CSF of five patients some 8 days after subarachnoid haemorrhage. Subarachnoid haemorrhage did not alter the production of prostaglandins by dog whole cortex or choroid plexuses in vitro, but production by pooled dissected cerebral arteries of PGE2 was increased and of 6 oxo F1 alpha was decreased. Intravenous indomethacin decreased prostaglandin production by cerebral tissues, and caused a marked decrease in the prostacyclin metabolite in CSF. The implications of our findings for the aetiology of cerebral vasospasm are discussed.

6-Ketoprostaglandin F1 alpha↗

Clinical studies of plasma PGF2 alpha M, the circulating prostaglandin F2 alpha metabolite.

Plasma concentrations of 13,14,dihydro-15-keto prostaglandin F2 alpha were measured (1) serially in six healthy young adults over 24-25 h; (2) in 62 male and 61 female subjects aged 3 to 64 years; (3) before and after a 12-h volley ball marathon in eight players and eight controls, and (4) in 41 geriatric in-patients aged 65 years and over. There was a small diurnal variation in plasma PGF2 alpha M concentration, levels being highest around 08.00 to 09.00 h. Concentrations did not change with age in fit subjects up to 64 years. Significantly increased concentrations were found in elderly sick patients, high levels in men being associated most often with pulmonary symptoms. Concentrations were not increased significantly by 12 h of competitive sport.

Adolescent↗

Hyperphenylalaninaemia of various types among three-quarters of a million neonates tested in a screening programme.

A total of 795 382 infants born in north London was screened for phenylketonuria using the Guthrie test between October 1969 and December 1978. During this period it became recognised that phenylketonuria is not a single disease entity but one that encompasses a number of disorders of differing clinical and biochemical severity. The overall incidence of persistent hyperphenylalaninaemia was of the order of 7 per 100 000 births (or 1 in 15 000) and all the early treated patients made normal developmental progress. During the study there was an appreciable fall in the incidence of uncomplicated transient hyperphenylalaninaemia with or without tyrosinaemia. This reduction coincided with the change in infant feeding practice in the UK which led to lower intakes of protein and phenylalanine. It was concluded that any infant found to have a persistent blood phenylalanine concentration of 240 mumol/1 (4 mg/100 ml) or greater should be followed closely.

Amino Acids↗

Pepsin 1 secretion in chronic peptic ulceration.

In patients with peptic ulceration, both vagal stimulation by insulin hypoglycaemia and stimulation by pentagastrin cause pepsin 1 to be secreted into gastric juice. There is a secretory threshold for pepsin 1, below which only pepsins 3 and 5 are secreted. Pepsin 1 accounts for an increasing proportion of the total peptic activity/ml of gastric juice as the total activity increases. Higher concentrations of pepsin 1 in the basal gastric secretion occurred significantly more frequently in patients with duodenal ulcer than with gastric ulcer. In these patients there may be an increased 'background' secretory drive.

Chronic Disease↗

Secretion of pepsins and hydrogen ions in the stomach of children undergoing cardiac surgery.

Gastric juice was collected from 27 children for 9 to 21 hr following cardiac surgery, from 4 further children during and following cardiac surgery, and from 3 children who had not undergone surgery. Each sample was analyzed for hydrogen ion and pepsin content. The pH of the postoperative secretions from 26 patients was 1.25 to 5.30, and the mean hydrogen ion concentration was 60.1 mmol/liter (range, 21.5 to 119.3 mmol/liter). The mean peptic activity (83.0 units/ml; range, 42.4 to 158.4 units/ml) was not age related and was significantly higher than that of the basal and pentagastrin-stimulated secretion and similar to that of vagally stimulated secretion of adults with peptic ulcer. The pepsin:hydrogen ion and pepsin 1:total pepsin ratios also resembled those of vagally stimulated secretion. During the first 90 min of cardiac surgery, the pH of aspirated gastric juice was 1.40 to 4.90, the hydrogen ion concentration was 15.8 to 72.3 mmol/liter, peptic activity was 39.2 to 164.0 units/ml (mean, 97.2 units/ml). Pepsin 1 was present in all samples. Aspirates from 3 unoperated children had low total peptic activity and only trace amounts of pepsin 1. Children from the age of 5.5 months thus have the capacity to secrete all the major pepsins, including pepsin 1. The findings suggest that vagal stimulation of gastric secretion was occurring during the postoperative period.

Adolescent↗

Cigarette smoking, chronic peptic ulceration, and pepsin 1 secretion.

The relationship between the secretion of pepsin 1 (the most electronegative of the pepsins), and the smoking habits of 219 patients has been investigated. Significantly more cigarette smokers with peptic ulceration (72.5%) secreted pepsin 1 in greater than trace amounts after pentagastrin or histamine than did non-smokers with ulceration (51.2%). Differences of a similar order were found for men with duodenal ulcer, women with duodenal ulcer, and all patients with gastric ulcer, but the difference was statistically significant only for men with duodenal ulcer. Significantly more patients with peptic ulcer smoking six to 15 cigarettes/day secreted moderate or high concentrations of pepsin 1 than did heavier smokers or non-smokers. There was no significant association between cigarette smoking and pepsin 1 secretion among 74 patients without ulceration. Maximal acid output was not significantly related to smoking in any group studied. The findings add to the increasing body of evidence linking pepsins and pepsin 1 with the pathogenesis of peptic ulceration.

Adult↗

Pepsin 5 in gastric juice: determination and relationship to the alkali-stable peptic activity.

Pure human pepsins 1 and 3 are inactivated by incubation at pH 7.1-7.3 for 30 minutes, losing 90% or more of activity. Pepsin 5 is alkali-stable, retaining 100% of activity. Mixtures of pure pepsins 1 and/or 3 with pepsin 5 were found to have greater alkali-stable activity than predicted. Two published methods for determining the alkali-stable fraction of the peptic activity of gastric juice gave, respectively, in our hands values of 45.4-80.0% and 27.5-43.9% of the total activity. These values seemed too high to be attributable only to pepsin 5 in gastric juice, as agar gel electrophoresis shows pepsin 3 to have the principal activity. Electrophoretograms of alkaline incubated gastric juice revealed that large amounts of pepsin 3 retained activity as well as pepsin 5, and a proteolytic zone "4" appeared between them. Alkali inactivation thus does not allow the estimation of pepsin 5 individually in gastric juice. Pepstatin, at a final concentration of 100 to 170 pmol/ml, may be used to estimate pepsin 5 in gastric juice and gave values of 18.0 to 27.6% of the total peptic activity. Pepsin 5, in gastric juice and in mixtures of pepsins, appears to protect pepsin 3 from alkaline-inactivation, and to a lesser extent from pepstatin inhibition.

Alkalies↗

Ovalbumin digestion by human pepsins 1, 3 and 5.

1. Of the three major human pepsins, pepsin 1 has greater proteolytic activity towards ovalbumin than has pepsin 3. Pepsin 5 has low activity towards this substrate. 2. Proteolytic pH-activity curves show only on pH maximum, about pH 1.4 for pepsin 1, pH 1.4--1.5 for pepsin 3 and pH 1.2--1.4 for pepsin 5. The curve for pepsin 3 has a shoulder between pH 2.4 and 3.4. 3. The rate of digestion of ovalbumin by pepsin 1 is approximately three times slower than are those of bovine haemoglobin or human globin. 4. The results suggest that there may be a physiological advantage in having more than one pepsin.

Electrophoresis, Agar Gel↗