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Biomedical subjects

V Marks

Publications and source records attributed to V Marks.

At least 235 records · Page 13Linked to original sources

Molecular forms of somatostatin in normal subjects and in patients with pancreatic somatostatinoma.

Two patients with somatostatin-secreting pancreatic tumours are described, one presenting with hypoglycaemia due to hyperinsulinism, and the other with Cushing's syndrome due to ectopic ACTH production. When plasma from these patients was subjected to gel chromatography under conditions designed to prevent somatostatin binding to larger proteins, a peak of monomeric immunoreactive somatostatin was observed as well as several large molecular weight forms. These larger forms of somatostatin could be dissociated into monomeric somatostatin by dithiothreitol. Similar studies on plasma obtained from normal subjects also showed heterogeneity of circulating somatostatin. Extracts of tumour tissue from both patients contained predominantly monomeric somatostatin, but only small amounts of high molecular weight somatostatin which differed from the profile seen in plasma. The site(s) of origin of the large molecualr weight forms of somatostatin seen in plasma and their relative biological activities remain to be established.

Adenocarcinoma↗

Immunoreactive somatostatin changes during insulin-induced hypoglycaemia and operative stress in man.

Little is currently known about the factors controlling somatostatin secretion. A radioimmunoassay has been developed that is sufficiently specific and sensitive to be used for physiological studies of circulating levels in man. During insulin-induced hypoglycaemia a rise in plasma somatostatin was seen in each of ten subjects studies. Although this paralleled the rise in circulating glucagon and growth hormone, no individual relationships were found either between these variables or to any change in cortisol or insulin C-peptide. In contrast no rise in somatostatin was seen during surgical stress. Thus, contrary to expectation, circulating somatostatin levels can be altered by metabolic stimuli. It seems likely that this peptide may serve an endocrine as well as a paracrine role since its modulating effects may occur not only near to but also at a distance from the site of secretion. It is not yet clear whether the somatostatin measured comes from the hypothalamus, any other part of the central nervous system or the gastrointestinal tract.

Adult↗

Plasma steroid levels after intra-articular injection of prednisolone acetate in patients with rheumatoid arthritis.

Eight patients with rheumatoid arthritis received an intra-articular injection of either 50 mg or 100 mg of prednisolone acetate into the knee joint. After the injection plasma levels of prednisolone were measured by radioimmunoassay and plasma cortisol levels were estimated fluorimetrically. Peak prednisolone levels were reached at between 2 and 4 hours after the intra-articular injection at both dosage levels, though the peak was higher with the larger dose. The 50 mg dose did not have any effect on the plasma cortisol level at 24 or 48 hours, but there was some suppression of plasma cortisol levels for up to 48 hours after the 100 mg dose.

Arthritis, Rheumatoid↗

Prednisolone absorption in acute colitis.

Peak plasma levels were reduced after an oral dose of 40 mg prednisolone in six patients with severe acute colitis as compared with six normal subjects, though total absorption appeared to be similar; the findings suggest that prednisolone absorption was delayed in acute colitis. A dilutional fall in plasma albumin was observed in normal subjects and in the patients after 40 mg prednisolone by mouth.

Acute Disease↗

Serum immunoreactive trypsin concentrations in diabetic children.

Serum immunoreactive trypsin (SIT) concentrations measured in 616 children with diabetes of recent onset were low, in both boys and girls, in comparison with reference ranges established in patients with non-diabetic, non-infectious illnesses. The mean SIT concentration was 60% of the mean reference level in children tested within three weeks of the onset of diabetes, and about 40% in patients tested six months after the onset of diabetes. Very low SIT levels were found in about 10% of patients, most of whom had no measurable SIT by the assay procedure employed. These very low SIT concentrations were more frequent in older children aged 6-15 years, and in children tested at about 5-6 months after onset. Repeat tests on some of the children showed that the very low SIT levels were generally present for only a limited period.

Adolescent↗

Evidence for preferential stimulation of gastric inhibitory polypeptide secretion in the rat by actively transported carbohydrates and their analogues.

A rat intestinal perfusion technique has been used to assess the ability of a number of monosaccharides, monosaccharide analogues and disaccharides to stimulate intestinal release of immunoreactive gastric inhibitory polypeptide (GIP). Perfusates containing glucose, sucrose, galactose, maltose, 3-O-methylglucose or alpha- or beta- methylglucoside at concentrations of 100 mmol/l in Krebs-Ringer phosphate buffer (KRP) produced significant stimulation of GIP release compared with the control perfusions with KRP alone (P less than 0.02). Mannose, 6-deoxygalactose, 2-deoxyglucose, myoinositol, fructose or lactose (100 mmol/l of each) did not stimulate GIP release compared with controls. There was no significant difference in the ability of sucrose, maltose or beta-methylglucoside (100 mmol/l of ach) to release GIP compared with 100 mmol glucose/l, but galactose, 3-O-methylglucose and alpha-methylglucoside (100 mmol/l of each) produced significantly lower GIP responses than did glucose (P less than 0.02). Addition of 5 mmol phloridzin/l to a perfusate containing 50 mmol glucose/l prevented intestinal absorption of glucose and abolished the GIP response. The molecular configuration of monosaccharides which have the ability to stimulate GIP release agreed well with the structural requirements for active transport by the sodium-dependent hexose pathway.

Animals↗

Variation in plasma prednisolone concentrations in renal transplant recipients given enteric-coated prednisolone.

Renal transplant recipients receiving intermittent haemodialysis and kept under normal ward conditions showed appreciable differences in plasma prednisolone concentrations after therapeutic doses of enteric-coated prednisolone tablets. This gross day-to-day variation occurred irrespective of the dosage used. Breakfast given before prednisolone tended to reduce the rate of absorption of the drug, the effect being quantitatively most pronounced with large doses. Haemodialysis had no apparent effect on the elimination of prednisolone from plasma. Such erratic blood concentrations of prednisolone as observed in these patients, possibly resulting from variable absorption, may be potentially hazardous. Hence use of enteric-coated tablets in renal transplant recipients should be viewed with caution.

Adolescent↗

The effect of oral galactose on GIP and insulin secretion in man.

The insulinotropic effect of 50 g galactose given orally to 5 normal volunteers on two occasions--once with and once without a period of hyperglycaemia produced by an intravenous glucose infusion--was studied. Oral galactose caused a rise in plasma GIP from fasting levels of 260 +/- 50 ng/l (mean +/- S.E.M.) to a maximum of 900 +/- 65 ng/l 30 min after ingestion, but in the presence of induced hyperglycaemia the GIP response was significantly diminished and delayed (maximum plasma GIP levels 595 +/- 110 ng/l at 45 min, p less than 0.05). The insulin response to galactose was greatly enhanced by IV glucose (mean area under plasma insulin curve with galactose alone 236.5 +/- 66.0, with galactose + IV glucose 451.9 +/- 81.6, p less than 0.025). The mean rise in plasma galactose was significantly lower in the presence of IV glucose (mean peak level 1.97 +/- 0.28 mmol/l with galactose alone, 0.69 +/- 0.16 mmol/l galactose + IV glucose, p less than 0.025). Oral galactose caused the release of GIP, which is powerfully insulinotropic in the presence of moderate hyperglycaemia. The lower plasma GIP and galactose levels observed following oral galactose in the presence of IV glucose may be accounted for either by postulating that insulin inhibits the absorption of oral galactose, or that insulin exerts a negative feed-back control on GIP release and accelerates galactose disposition in the body.

Administration, Oral↗

The effect of unabsorbable carbohydrate on gut hormones. Modification of post-prandial GIP secretion by guar.

Five healthy volunteers and 6 diabetics were given a mixed test meal on two occasions--once with and once without 10 g guar flour. Addition of guar caused a 47% decrease in maximum post-prandial GIP levels, a 48% decrease in blood glucose and a 48% decrease in plasma insulin in normal subjects. In diabetics, addition of guar caused a 30% reduction in maximum post-prandial GIP and 58% decrease in blood glucose. Four normal and 6 diabetic subjects were given a predominantly carbohydrate meal, again with and without 10 g guar. Addition of guar caused a 78% decrease in blood glucose and a 59% decrease in plasma insulin in normal subjects. In diabetics addition of guar caused a 71% decrease in maximum post-prandial plasma GIP and a 68% decrease in blood glucose. Lowering of post-prandial blood glucose, plasma insulin and GIP levels by guar was statistically significant in every case. Addition of guar to the predominantly carbohydrate meal caused a decrease in total plasma GLI in both normal and diabetic subjects but reached statistical significance only in the normal subjects. There was a highly significant correlation (r = 0.83; p less than 0.0005) between peak post-prandial insulin levels in normal subjects and the corresponding plasma GIP concentration. The reduction of GIP or GLI secretion may, therefore, be partly responsible for the smaller rise in plasma insulin observed in normal volunteers when guar is added to meals.

Adult↗

The influence of antigen properties on the conditions required to elute antibodies from immunoadsorbents.

Immunoadsorbents were used to purify a number of antibodies. Using pH 2.0 acid conditions alone it was possible to elute antibodies raised against human growth hormone (HGH) and Fc fragments from such immunoadsorbents with 50% or better recovery of antibody activity. However, to elute antibodies raised against triiodothyronine and cortisol required 6 M guanidine HCl, pH 2.0. The avidities of the purified antibodies were similar to those of the non-purified antibodies. The purified antibodies were stable in solution at 4 degrees C for at least six months.

Animals↗

A comparison of the ability of beta-galactosidase and horseradish peroxidase enzyme-antibody conjugates to detect specific antibodies.

The ability of two different enzyme-antibody conjugates to detect specific antibodies has been compared. beta-Galactosidase was conjugated to antibodies raised against rabbit Fc fragments using m-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS). Horseradish peroxidase (HRP) was conjugated to part of the same batch of antibodies using the periodate method. The beta-galactosidase and HRP labels enabled detection of approximately 8 fmoles and 4 fmoles respectively of human growth hormone (HGH) antibodies, when their enzyme activities were measured spectrophotometrically. The detection limit of the beta-galactosidase label was increased 4-fold when a fluorimetric detection system was employed.

Animals↗

Serum immunoreactive trypsin concentrations in infectious and non-infectious illnesses and in juvenile diabetes.

Serum immunoreactive trypsin (SIT) concentrations were measured in 244 patients with infectious illnesses and in 281 children with diabetes of recent onset. Results were compared with reference ranges established in 107 patients with non-infectious, non-diabetic illnesses, in whom SIT concentrations were found to increase with advancing age. Reduced or undetectable concentrations of SIT were associated with diabetes in children and with a few cases of severe childhood infection. Increased SIT concentrations were associated with virologically confirmed cases of infection with mumps and Coxsackie B virus infection, and with clinical diagnoses of mumps, PUO, and meningitis in children, and with Bornholm disease, cardiac infection, and respiratory infection in adults. It is suggested that silent invasion of the exocrine pancreas with elevation of the SIT concentration may accompany infection by Coxsackie B, mumps, and, possibly, other viruses.

Adolescent↗

Enzyme immunoassay: a review.

In the last few years, the use of enzyme labels in immunoassays has been investigated. The aim of this review is to evaluate critically the role of such labels in clinical biochemistry. Special attention has been given to the problems involved in preparing enzyme labels and the ways in which such labels can be used in a variety of heterogeneous and homogeneous assay systems.

Antibodies↗

Improved double-antibody enzyme immunoassay for methotrexate.

We report an enzyme immunoassay procedure for methotrexate measurement that takes less than 3 h to perform. beta-D-Galactosidase (EC 3.2.1.23) from Escherichia coli was conjugated to methotrexate by means of the mixed anhydride reaction. Bound and free labeled drug were separated by a preincubated cubic complex of first and second antibody. The enzyme activity of the bound fraction was measured with o-nitrophenyl-beta-D-galactopyranoside as substrate. The standard curve covered the range 1 to 10 micrograms of methotrexate per liter. One microgram of methotrexate per liter inhibited binding of the tracer by 17%. The assay is specific for methotrexate in the presence of folinic acid (citrovorum factor), folic acid, tetrahydrofolic acid, and other methotrexate metabolities. Intra- and inter-assay CVs were less than 5 and 10%, respectively. Results obtained with this enzyme immunoassay method agreed well with those obtained with an established radioimmunoassay method.

Cross Reactions↗