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Biomedical subjects

V Marks

Publications and source records attributed to V Marks.

At least 37 records · Page 2Linked to original sources

Inappropriately elevated plasma insulin-like growth factor II in relation to suppressed insulin-like growth factor I in the diagnosis of non-islet cell tumour hypoglycaemia.

The diagnosis of non-islet cell tumour (hypoinsulinaemic) hypoglycamia has been complicated by contradictory biochemical evidence. Although insulin-like growth factor II (IGF-II) has been identified as the hypoglycaemic agent, plasma levels are often not elevated. In this study specific radioimmunoassay procedures for the measurement of IGF-I and IGF-II are described. Reference data on plasma IGF-II concentrations in relation to a wide range of IGF-I levels have been accumulated using plasma samples from acromegalic, hypopituitary and insulinoma (i.e. hyperinsulinaemic hypoglycaemia) patients as well as normal subjects from all age groups. The reference data indicate that a low plasma IGF-I value is normally associated with a relatively low plasma IGF-II level. Within a group of hypoinsulinaemic hypoglycaemia patients, a small number, invariably with evidence of a neoplasm, had low plasma IGF-I concentrations but apparently normal IGF-II levels. We propose that, in such cases, an apparently normal plasma IGF-II value is inappropriately high for the low plasma IGF-I level and, in association with non-ketotic hypoinsulinaemia and suppressed plasma growth hormone (GH), is diagnostic of a non-islet cell tumour as the cause of hypoglycaemia.

Adult

Hyperinsulinaemic hypoglycaemia in small for dates babies.

Blood glucose concentrations were measured prospectively in 27 small for dates infants in the first 48 hours after birth: 10 infants became hypoglycaemic. Of these, five had inappropriately raised plasma insulin concentrations. Plasma free fatty acids were lower and carbohydrate intake higher in these five infants, further supporting the diagnosis of hyperinsulinism. The hypoglycaemia recurred in four of the five hyperinsulinaemic infants, but in none of those who were not hyperinsulinaemic. Hyperinsulinism is common in small for dates babies. It is important to recognise this because hypoglycaemia is likely to recur and appropriate treatment is needed to prevent long term sequelae.

C-Peptide

Insulin-like growth factor 1 in patients with hypoglycaemia.

Plasma insulin-like growth factor 1 (IGF-1) concentrations were measured in a group of patients with hypoglycaemia due to endogenous hyperinsulinism, and compared with those in a group of patients matched for age and sex with hypoglycaemia and appropriately suppressed insulin levels. Insulin-like growth factor 1 concentrations were significantly higher in the hyperinsulinaemic hypoglycaemic group than in either the hypoinsulinaemic hypoglycaemia group or a group of euglycaemic control subjects. These data provide further evidence that insulin promotes IGF-1 production and release from the liver.

Adolescent

Stimulatory effects of glucagon-like peptides on human insulinoma cells and insulin-releasing clonal RINm5F cells.

Insulin-releasing effects of glucagon-like peptides, glucagon and various nutrients were examined using tumour cells from a freshly resected human insulinoma and RINm5F cells. Insulin release by human insulinoma cells or RINm5F cells was not affected by 16.7 mM glucose. Both cell types exhibited secretory responses to 20 mM alanine, 25 mM K+ and 7.6 mM Ca2+. Insulin release by human insulinoma cells was enhanced at 2 x 10(-7) M by glucagon, GLP-1[1-37], GLP-1[7-36] and its N- and C-terminal fragments GLP-1[7-14] and GLP-1[31-37]. The intact peptides (2 x 10(-6)-2 x 10(-12) M) also stimulated insulin release by RINm5F cells, but neither of the fragments enhanced secretion. The cyclic AMP content of human insulinoma cells and RINm5F cells was increased by glucagon. GLP-1[7-36] (2 x 10(-8)-2 x 10(-10) M) increased cyclic AMP in RINm5F cells, but no additional effects were noted in these or human insulinoma cells. These results suggest that GLP-1[7-36] stimulates insulin release by a direct action on human and rat B-cells, partly involving modulation of intracellular cyclic AMP.

Adult

Circulating and secretory antibodies to specific food proteins in adults.

Indirect enzyme-linked immunosorbent assays (ELISA) for the detection of antibodies to gliadin, beta-lactoglobulin and ovalbumin have been developed. Specific antibody immunoglobulin levels were quantified. Serum and saliva samples were collected from twenty normal subjects and measured for the presence of specific antibodies. For each subject food intake was calculated from a 7-d weighed food inventory record. The total IgG level was 14.2 +/- 4.3 mg/ml (mean +/- s.d.). Levels of beta-lactoglobulin IgG were significantly lower than ovalbumin IgG levels (130 +/- 130 micrograms/ml versus 637 +/- 703 micrograms/ml, P less than 0.01). Gliadin IgG levels were also significantly lower than ovalbumin IgG levels (262 +/- 398 micrograms/ml versus 637 +/- 703 micrograms/ml, P less than 0.05). However, no significant difference was observed between gliadin and ovalbumin IgA levels in the subjects (29 +/- 39 per cent versus 56 +/- 122 per cent). A significant correlation was observed between ovalbumin IgG levels in serum and dietary intake of egg protein (r = 0.46, P less than 0.05). No other significant correlations were observed.

Adult

Near-patient testing: implications for laboratory-based professions.

The current upheaval being experienced by the National Health Service in the UK is due partly to political and partly to technological changes in the mode of delivery of health care. The two can not be separated completely, but the implications for laboratory-based health care professions of technological changes that have occurred in their specialty, mainly within the last 10 years, are considered. These have made it increasingly possible to carry out previously complicated analytical manoeuvres outside the confines of a well-founded laboratory, but in doing so have brought with them problems as well as advantages for the providers of health care, as well as for its recipients--i.e. the patients.

Emergency Medical Services

The extraction and purification of a peptide from rat insulinoma tissue.

A peptide was extracted and purified from rat insulinoma tissue which, although similar, was not identical to normal rat C peptides. The purity of the peptide, called rat insulinoma peptide (RIP), was investigated using polyacrylamide gel electrophoresis, isoelectric focusing and high-performance liquid chromatography. It appears to contain two peptides similar to each other but differing in their isoelectric points. The peptides as assessed by fast atom bombardment mass spectrometry have molecular masses in the region of 1982 Da, given a chain length of approx. 22 amino-acid residues. Evidence obtained using an established rat C peptides radioimmunoassay suggests that RIP shares a common C-terminus with rat C peptides. The antiserum produced to RIP was used to develop a radioimmunoassay using a tracer prepared by iodinating purified tyrosylated RIP.

Adenoma, Islet Cell

The anterograde and retrograde infusion of glucagon antibodies suggests that A cells are vascularly perfused before D cells within the rat islet.

We have suggested that the order of cellular vascular perfusion within the islet is important in the regulation of islet hormone secretion. Anatomically, the A and D cells appear to be randomly dispersed throughout the mantle. Although islet capillary blood flow is known to be from the B-cell core to the A- and D-cell mantle, it has not yet been established whether the cells of the mantle may influence one another vascularly. Rat pancreata were perfused in vitro anterogradely and retrogradely with or without glucagon antibody in order to determine the order of cellular perfusion and interaction between the A and D cells in the islet mantle. Anterograde infusion of glucagon antibody did not affect insulin secretion, but rapidly decreased somatostatin secretion -46 +/- 8%, (p less than 0.005). Retrograde infusion of glucagon antibody decreased insulin secretion (-27 +/- 8%, p less than 0.005) but had no effect upon somatostatin secretion. This study not only confirms a core to mantle islet perfusion but also establishes that the A cell precedes the D cell in the terms of vascular perfusion. Thus within the islet, vascular borne insulin regulates the release of glucagon, which in turn, regulates the release of somatostatin. Somatostatin is vascularly neutral owing to its downstream position in the sequence (B to A to D) of cellular perfusion.

Animals

The quantitation by radioimmunoassay of 2'-deoxyuridine 5'-triphosphate in extracts of thymidylate synthase-inhibited cells.

A radioimmunoassay (RIA) for dUTP, with a sensitivity of 3.78 fmol, has been developed. The antibody cross-reacted with dTTP so that affinity purification of the immunoglobulin G fraction was required before its use in the RIA. Cross-reactivity with UTP and with mono- and diphosphodeoxyuridylates has necessitated respectively sodium periodate oxidation and anion exchange chromatography of cell extracts, prior to RIA quantitation of dUTP directly in fractions from the chromatography column. Mean recovery rate of a range of concentrations of extracted dUTP standard taken through the entire procedure is 63.7% (7.8-31.3 pmol dUTP) although at a lower concentration (3.11 pmol) the recovery was only 36.2%. Results are reproducible with CV values of between 3.1 and 9.5%. The assay has been used to assess the presence of dUTP in A549 human lung carcinoma cells exposed to the thymidylate synthase inhibitor CB3717. The high sensitivity of the quantitation step has made it possible to measure dUTP in relatively small numbers (10(6)) of cells.

Antineoplastic Agents

Biosynthetic human growth hormone in burned patients: a pilot study.

A 15-day, open trial was conducted in 12 adult burned patients of whom six were randomly allocated to form a control group and six to receive biosynthetic human growth hormone (somatropin). All were fed enterally and treated according to a standard burn protocol. The mean age, burn size, energy and nitrogen intakes were well matched in each group. The resting energy expenditures (REE) were comparable in each group and the REEs exceeded the calculated basal energy expenditures by a mean of 36.8 +/- 4.1 per cent for both groups. Blood urea values were significantly lower in somatropin-treated patients but there was no significant difference in nitrogen balance, protein oxidation or the rate of plasma protein recovery between the two groups. The basal plasma insulin concentration and basal insulinogenic index were significantly higher in somatropin-treated patients but insulin release, in response to injected glucose, was comparable in both groups. All patients had impaired glucose disposal due to insulin resistance but the area under the glucose curve increased significantly during somatropin treatment. It is concluded that somatropin administration did not significantly improve nutrition in burned patients but has been shown to exacerbate the existing insulin resistance.

Adult

Enhanced chemiluminescent enzyme immunoassay for cannabinoids in urine.

An enhanced chemiluminescent enzyme immunoassay was developed for the detection of cannabinoids in urine. It utilises an antiserum specific for tetrahydrocannabinol and its major metabolite, a donkey anti-sheep antiserum and a horseradish peroxidase labelled antigen conjugate. The bound enzyme is detected via its catalytic activity on the chemiluminescent luminol-H2O2 reaction in the presence of an enhancer. This immunoassay employs mild experimental conditions and is extremely sensitive (0.13 microgram l(-1), making it suitable for the detection of cannabinoids in samples obtained several days following drug use. None of several medicinal and other drugs of abuse tested interfered in the assay. Greater sensitivity and simplicity make it a feasible non-isotopic alternative to radioimmunoassay and it is amenable to automation and routine screening to large sample batches.

Cannabinoids