Search PubMed⌕ Search

Biomedical subjects

G A Turner

Publications and source records attributed to G A Turner.

At least 37 records · Page 2Linked to original sources
PubMed1996

Human ovarian tumour cells can bind hyaluronic acid via membrane CD44: a possible step in peritoneal metastasis.

Our previous studies have suggested that the interaction between hyaluronic acid (HA) on peritoneal mesothelial cells and the membrane adhesion molecule, CD44, on ovarian tumour cells could be important in ovarian cancer metastasis. In order to study this further, adhesion of six ovarian tumour lines to HA coated on to a plastic surface was investigated. Four lines bound to the HA coat and two lines did not. The adhesive lines were those that expressed high amounts of CD44, but the degree of adhesion was not closely correlated with CD44 expression. The results suggested that different tumour lines had different affinities for HA. Treatment of the HA coat with hyaluronidase substantially reduced adhesion. Adhesion was also partially reduced if the tumour cells were preincubated with either soluble HA, or anti-CD44 antibodies directed against the HA binding region. An antibody against a non-HA binding region only slightly blocked adhesion at high antibody concentrations. Only the CD44H isoform was detected by immunoprecipitation on the tumour cells. These results suggest that ovarian tumour cells can attach to immobilised HA via CD44H on the cell membrane.

Antibodies↗
PubMed1996

An improved ELISA for the determination of sialyl Lewis(x) structures on purified glycoconjugates.

The membrane carbohydrate antigen, sialyl Lewis x (sLe(x)), is involved in cellular adhesive interactions in many diseases, such as cancer, inflammation and thrombosis. This antigen is also found on soluble macromolecules, such as serum glycoproteins, but the precise role of soluble sLe(x) in modifying disease processes, or reflecting the pathological changes is still unclear. Although methods were previously reported for the measurement of soluble sLe(x), many of these were not well characterised, measurements were mainly made on mixtures of molecules, and the anti-sLe(x) antibodies were used at concentrations that made the assay expensive. In this study an ELISA has been devised that detects sLe(x) in purified soluble glycoconjugates using the anti-sLe(x) antibody, CSLEX I. Commercially-available haptoglobin (Hp) and synthetic complexes of Lewis antigens with polyacrylamide were used as model substances in developing the procedure. Key steps were washing the antibody/antigen complex with ten times diluted salt solution to prevent dissociation of the complex and the use of bovine serum albumin for blocking non-specific interactions. The assay was shown to be very specific, its precision was in the range 6-12%, and it could detect less than a pmol of sLe(x). It could also distinguish between different densities of sLe(x) on the same amount of glycoconjugate. Determination of sLe(x) in Hp isolated from small groups of healthy individuals, cancer patients, and rheumatoid arthritis sufferers suggested that the antigen expression is increased in disease. This method, which is an improvement on those previously described will be useful for determining sLe(x) in many different types of soluble glycoconjugate, and used in combination with synthetic carbohydrate polyacrylamide complexes, will help to standardize measurements of soluble sLe(x) in the future.

Adult↗
PubMed1996

A comparison of intramuscular ketorolac with indomethacin suppositories in the treatment of pain after oral surgery.

The analgesic effects of 30 mg intramuscular ketorolac were compared with those of rectal indomethacin in 100 mg and 200 mg doses in 66 patients in a single-blinded trial. Pain scores and the incidence of nausea and vomiting were assessed at 30, 60 and 120 minutes postoperatively, at discharge (4 hours) and on the evening of surgery. Area under the curve of pain scores versus time for pain at 30, 60 and 120 minutes postoperatively was significantly lower in the ketorolac group compared to indomethacin 100 mg and 200 mg groups. There were no significant differences in the pain scores at discharge or at home on the evening of surgery. At 60 minutes postoperatively there was significantly more nausea and vomiting in the indomethacin 200 mg group; at all other time-points there was no significant difference between the groups with regard to nausea and vomiting. The power of the study to determine the significance of side-effects between the groups was low.

Adult↗
PubMed1996

Electrocorticographic activity during repeated vs continuous hypoxia in piglets.

To assess the effects on brain activity of repeated vs continuous hypoxia, 16, 10- to 22-day-old piglets were instrumented chronically for electrocortical and arterial pH and gas tension measurements. They inhaled 10% or 6% O2 in N2 for 21 min, either continuously, or during seven, 3 min exposures interrupted by 3 min recovery periods in air, all while behaving naturally within a sealed, temperature controlled, plexiglass box. An isoelectric electrocorticogram (ECoG) and/or seizures, related to the onset of hypoxia, occurred repeatedly in 6 of the 10 exposures to 6% repetitive hypoxia, only twice in 8 exposures to 6% continuous hypoxia, and never in 10% hypoxia. A frequency analysis of the ECoG, excluding all sections exhibiting isoelectric and seizure activity, revealed no changes with 10% hypoxia, but a shift towards the lower bands during both repetitive and continuous 6% hypoxia. The extent of these shifts was greater in records that also displayed isoelectric ECoG and/or seizures. The ECoG spectrum recovered at the end of the hypoxic exposure, but not when isoelectric ECoG and/or seizures coexisted. We conclude that repeated, frequent episodes of hypoxia are more detrimental than a prolonged single event, and may contribute to the occurrence of Sudden Infant Death.

Animals↗
PubMed1995

Decreased branching, increased fucosylation and changed sialylation of alpha-1-proteinase inhibitor in breast and ovarian cancer.

Proteolytic enzymes could be very important in spread of cancer, but the role of the body's natural inhibitors of these enzymes in this process is unknown. One such inhibitor is the serum glycoprotein, alpha-1-proteinase inhibitor (API). In previous studies we showed that the fucose-specific lectin, lotus tetragonolobus, extracted high amounts of API in cancer when patients were unresponsive to treatment. The aim of this study was to determine whether the carbohydrate structure of API is altered in cancer. API was isolated from the sera of healthy women and women with breast or ovarian cancer. By means of high-performance anion-exchange chromatography, cancer API was shown to contain more fucose and less N-acetylglucosamine than healthy API. Further investigation of the purified specimens using a lectin-binding assay suggested that the cancer API was less branched and contained more alpha 2-6 and less alpha 2-3 sialic acid. Observations from both methods were consistent with an increase in bi-antennary chains terminating in alpha 2-6 sialic acid and possibly more alpha 1-6 fucose in the core of the unit. These distinctive changes could have important consequences for the function of API in cancer and may help to develop more precise markers for monitoring pathological progression in this disease.

Adenocarcinoma, Mucinous↗
PubMed1995

Expression of cell adhesion molecules on ovarian tumour cell lines and mesothelial cells, in relation to ovarian cancer metastasis.

A major route for the spread of ovarian cancer is by the attachment of tumour cells to the mesothelium lining in the peritoneal cavity. The expression of various adhesion molecules has been measured on freshly-prepared mesothelial cells, two mesothelial cells lines and 13 established ovarian tumour cell lines. The integrins beta 1 and beta 3, ICAM-1, and CD44 were detected on all mesothelial preparations and on many or all of the tumour lines. VCAM-I was expressed exclusively on the mesothelial cells and Lewis x was expressed on half of the tumour lines. There was low or no expression of sialyl Le(x), sialyl Le(a), integrins alpha 4, beta 1, beta 4, or E and P selectins. Only CD44 expression was significantly affected by trypsin treatment. From the known interactions of adhesion molecules, the results suggest that CD44, and beta 1 and beta 3 integrins may be important in tumour/mesothelial interactions.

Carrier Proteins↗
PubMed1995

Hyaluronic acid secreted by mesothelial cells: a natural barrier to ovarian cancer cell adhesion.

The adhesion to mesothelial monolayers of eight cultured ovarian tumour cell lines was studied in multiwell plates as a model for some of the interactions of ovarian cancer in the peritoneal cavity. When only the upper half of the conditioned medium (CM) from a confluent mesothelial cell culture was aspirated, the adhesion of the tumour cells was low (3.5%-36%). When the medium was removed completely the adhesion increased. The tumour cell lines showing the greatest enhancement of adhesion were those which had previously been shown to express the highest amounts of CD44. By adding erythrocyte suspensions to mesothelial cells it was shown that there was a pericellular coat around the mesothelial cells that could be destroyed by aspirating the medium, or by treating the medium with hyaluronidase (Hase). Treatment of the CM with Hase also considerably increased tumour cell adhesion. Furthermore, CM was shown to contain high amounts of hyaluronic acid (HA). HA blocked adhesion in the absence of CM, but the effect was not as large as that produced by the pericellular coat. It is proposed that pericellular HA produced by mesothelial cells has an important role in the invasion of ovarian tumour cells in the peritoneal cavity.

Cell Adhesion↗
PubMed1995

Glycosylation of alpha-1-proteinase inhibitor and haptoglobin in ovarian cancer: evidence for two different mechanisms.

The change in glycosylation of the two acute-phase proteins, alpha-1-proteinase inhibitor (API) and haptoglobin (Hp), in progressive ovarian cancer is different. This has been shown by monosaccharide analysis and lectin-binding studies of proteins purified from serum. In the glycan chains of API, there is decreased branching (more biantennary chains), less branches ending in alpha 2-3 sialic acid, more branches ending in alpha 2-6 sialic acid and more fucose, probably linked alpha 1-6 to the core region. On the other hand, Hp shows increased branching (more triantennary chains), more branches ending in alpha 2-3 sialic acid, less branches ending in alpha 2-6 sialic acid, and more fucose, probably in the alpha 1-3 linkage at the end of the chains. This is surprising because API and Hp are thought to be glycosylated by a common pathway in the liver. We have also shown that the fucose-specific lectin, lotus tetragonolobus, extracts abnormal forms of both Hp and API in ovarian cancer, but the expression of this Hp is related to tumour burden and the expression of this API is related to lack of response to therapy. It is suggested that this difference in the behaviour of API and Hp in ovarian cancer may be associated with the different changes in their glycosylation. Of the many mechanisms that could explain these findings, a likely one is that a pathological process is removing API with triantennary chains from the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbohydrate Conformation↗
PubMed1995

Haptoglobin. A potential reporter molecule for glycosylation changes in disease.

The acute-phase protein, haptoglobin, is elevated in many diseases; however, its glycosylation also changes, and the type of change observed can vary with disease. Increased fucosylation is a common finding, and the fucose-specific lectin, lotus tetragonolobus, can be used to differentiate different diseases (eg inflammatory conditions, liver diseases), and to monitor disease activity in cancer. Changes in N-acetyl neuraminic acid and N-acetylglucosamine suggest that particular carbohydrate structures predominate in certain diseases. Because haptoglobin glycosylation provides a record of previous intracellular events, it will help to improve our understanding of pathological processes and provide potential clinical markers for the future.

Acute-Phase Reaction↗
PubMed1994

A precise, rapid and sensitive in vitro assay to measure the adhesion of ovarian tumour cells to peritoneal mesothelial cells.

Ovarian cancer is the second most common gynaecological cancer in the UK, causing 2000 deaths per year. It spreads by shedding cells which attach to the mesothelial lining of the peritoneal cavity. In order to quantitatively study this interaction, a model system was developed in which mesothelial cells were cultured as monolayers in multiwell plates, and ovarian tumour cells were added that had been pre-labelled with a fluorescent dye (calcein). Synchronous interaction between the two populations was achieved by brief centrifugation at low g and the degree of attachment was measured on an automated fluorimeter after washing away the unbound cells. Using this procedure it was possible to measure tumour cell adhesion in 96 wells in 3-4 h. The reproducibility of the method was high even after short incubation times and the background absorbance was so low that the adhesion of less than a 1000 cells could be easily detected. The method works equally well for all ovarian tumour cell lines so far studied, and in preliminary experiments, it was shown that it can be used to screen for the effects of various blocking agents.

Cell Adhesion↗
PubMed1994

Monosaccharide composition of haptoglobin in liver diseases and alcohol abuse: large changes in glycosylation associated with alcoholic liver disease.

Liver damage through prolonged intake of high amounts of alcohol is a serious problem that affects many members of the population. The aim of this study was to investigate changes in the glycosylation of haptoglobin (Hp) resulting from alcoholic liver diseases. The monosaccharide composition was measured in Hp isolated from 48 healthy individuals, 15 alcohol abusers (AA); 25 patients with alcoholic liver disease, including those with alcoholic cirrhosis (ALD/AC), and 17 other patients with either chronic active hepatitis (AH) or primary biliary cirrhosis (BC). Fucose was elevated per mol of Hp in 70%, 44%, and 33% of the individuals in the ALD/AC, BC and AA groups, respectively. Fucose was not elevated in the AH group. N-acetylglucosamine was also elevated in the ALD/AC group. Expressing results per 3 mol of mannose suggested the presence of higher branching with increased fucose content in Hp from all the abnormal groups except the AH group. More structural information is required to develop the diagnostic potential of carbohydrate measurements of Hp in alcoholic liver diseases.

Acetylglucosamine↗
PubMed1994

Comparison of preoperative with postoperative lignocaine infiltration on postoperative analgesic requirements.

Ninety patients undergoing appendicectomy were allocated randomly to receive 1.5% lignocaine 15 ml with adrenaline infiltrated into the proposed wound line 3 min before incision, lignocaine 15 ml with adrenaline infiltrated into the wound on closure or no wound infiltration. After operation, all patients received pethidine by patient-controlled analgesia. Pain scores were assessed while supine and sitting on day 1 and 2 and the cumulative pethidine dose administered was recorded at 12, 24, 36 and 48 h after operation. There were no significant differences in the cumulative dose of pethidine required or pain scores between the three groups at any time point after operation. We conclude that pre-incisional infiltration with 1.5% lignocaine had no advantage compared with infiltration at wound closure or no wound infiltration in reducing postoperative analgesic requirements or pain scores after appendicectomy.

Adolescent↗
PubMed1994

Indomethacin as adjunct analgesia following open cholecystectomy.

Fifty patients scheduled for elective cholecystectomy were randomised to receive either indomethacin suppositories 200 mg p.r. at the end of anaesthesia, followed by 100 mg bd for three days, or placebo suppositories according to the same regimen. All patients were given intravenous pethidine via patient-controlled analgesia (PCA) postoperatively. The mean dose of pethidine required by the patients in the indomethacin group was significantly less than that used by the placebo group, the cumulative dose after three days being 530.7 mg (SD 664.0) and 1151.0 mg (682.0) for the indomethacin and placebo groups respectively. At the same time the patients in the indomethacin group had lower pain scores both at rest and with movement, though this was only statistically significant on the first day on movement. There was no statistical difference between the groups with respect to the incidence of nausea, indigestion, proctitis, volume of drainage from the wound drain, or width of bruising around the wounds. Serum creatinine levels were compared pre- and postoperatively where possible and showed no change in either group.

Analgesia↗