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Biomedical subjects

F Macdonald

Publications and source records attributed to F Macdonald.

At least 37 records · Page 2Linked to original sources
PubMed1992

Sodium-lithium countertransport activity and insulin resistance in normotensive IDDM patients.

In insulin-dependent diabetes (IDDM), an overactivity of sodium-lithium countertransport (Na+/Li+ CT) has been associated with the risk of nephropathy and hypertension, two conditions of insulin resistance. We investigated the sensitivity to insulin with a hyperinsulinemic (approximately 719 pM [approximately 100 microU/ml]) euglycemic clamp in two groups of normotensive nonproteinuric IDDM patients; 12 (10 men, 2 women) had high Na+/Li+ CT activity (mean 0.47, range 0.42-0.68 mmol/L red blood cells [RBC]/h, group 1) and 12 (9 men, 3 women) had normal Na+/Li+ CT activity (mean 0.24, range 0.12-0.31 mmol/L RBC/h, group 2). The two groups were similar in age (mean +/- SE 36 +/- 2 vs. 33 +/- 1 yr), duration of diabetes (19 +/- 3 vs. 18 +/- 2 yr), body mass index (26 +/- 0.8 vs. 24 +/- 0.6 kg/m2), arterial blood pressure (systolic/diastolic 121 +/- 4/79 +/- 2 vs. 122 +/- 3/77 +/- 2 mmHg), and glycemic control (HbA1 8.5 +/- 0.4 vs. 8.0 +/- 0.4%). Albumin excretion rate (AER) ranged between 4.7 and 148 (geometric mean 14) micrograms/min in group 1 and between 2.7 and 93 (geometric mean 11) micrograms/min in group 2. There were four microalbuminuric patients (AER greater than 30 micrograms/min) in each group. Whole-body glucose uptake was significantly reduced on average in group 1 compared with group 2 (41.6 +/- 2.2 mumol.kg-1.min-1 [7.48 +/- 0.4 mg.kg-1.min-1] vs. 49.6 +/- 2.2 mumol.kg-1.min-1 [8.93 +/- 0.4 mg.kg-1.min-1, P = 0.03), but some overlap existed between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Labelled antibody imaging in pancreatic cancer, cholangiocarcinoma, chronic pancreatitis and sclerosing cholangitis.

Pancreatic and biliary carcinomas are difficult to differentiate clinically from their benign counterparts, chronic pancreatitis and sclerosing cholangitis. Immunohistochemical differences in CEA expression have previously been demonstrated in these conditions. We have therefore investigated the use of a monoclonal anti-CEA antibody (11-285-14) in distinguishing between these conditions in vivo. Twenty-five patients with these four conditions underwent radioimmunolocalisation studies. Diagnosis was confirmed by laparotomy and biopsy (n = 21), CT scanning (n = 1) or ERCP (n = 3). Positive images were obtained in 11/12 pancreatic cancers and 2/3 biliary tumours. However, 4/8 cases of chronic pancreatitis and 1/2 cases of sclerosing cholangitis also had positive images. This high false positive rate suggests that antibody imaging is unable to differentiate reliably between benign and malignant pancreatico-biliary conditions.

Adenoma, Bile Duct↗
PubMed1990

Biodegradable emboli and antibody targetting of colorectal and gastric hepatic metastases: a pilot study.

The effect of degradable starch microspheres (DSM) on the passage of a low molecular weight marker through the liver of patients with metastases was compared with the passage of an anti-carcinoembryonic antigen monoclonal antibody. In all six patients studied DSM reduced the passage of the marker into the systemic circulation. In three patients who received labelled whole antibody, DSM had no effect. In two of three who received antibody fragments a similar delay to the low molecular weight marker was observed. This delay is likely to be a result of the smaller size of the fragments and may represent accumulation within the extravascular space.

Antibodies, Monoclonal↗
PubMed1988

Undifferentiated columnar cells on the gastric interfoveolar crest: a previously undescribed observation.

We have observed and defined morphometrically and histochemically an entity composed of groups of undifferentiated columnar cells on the interfoveolar crest of gastric mucosa. These cells are clearly distinct from either normal foveolar cells or regenerative epithelial cells associated with ulcer healing. They show a close association with atrophic gastritis, particularly in the presence of type 3 sulphomucin-secreting intestinal metaplasia. We have termed this the gastric tip lesion since it is observed only on the tips of the mucosal folds. This has not been described previously. We propose that these cells are the precursors of type 3 intestinal metaplasia and may also provide a link between this type of intestinal metaplasia and the intestinal variant of gastric adenocarcinoma.

Adenocarcinoma↗
PubMed1988

Expression of CEA, CA125, CA19-9 and human milk fat globule membrane antigen in ovarian tumours.

The expression of five different antigens in ovarian tumours was studied by means of an immunohistochemical test with anti-CEA, HMFG1 and HMFG2, NS19-9 and OC125 antibodies. Considerable variation was noted not only between different histological types and between tumours of one type but also between areas in a single tumour. HMFG1 and HMFG2 were the most reactive of all the antibodies; NS19-9 and OC125 were expressed by different populations of cells. It is concluded that specific combinations of antibodies are more effective both for the monitoring of ovarian cancer as well as for immunodiagnosis and treatment, than any single one used.

Adenocarcinoma↗
PubMed1987

Immunoadsorbent purification of carcinoembryonic antigen using a monoclonal antibody: a direct comparison with a conventional method.

Carcinoembryonic antigen (CEA) has been extracted and purified by two different methods from a single aqueous homogenate of liver metastases from a primary adenocarcinoma of the colon, thus enabling direct comparison to be made between a conventional technique using gel filtration and a monoclonal antibody immunoadsorbent method. Yield, immunoreactivity and purity have been determined in both cases by direct weighing, enzyme-linked immunoadsorbent assay, radioimmunoassay and SDS-polyacrylamide gel electrophoresis. Reactivity of the antigen with monoclonal and polyclonal anti-CEA antibodies recognising different epitopes was analysed by Western blotting. There appears to be no significant difference in immunoreactivity or purity by these criteria, but the immunoadsorbent method gave a higher yield of CEA for far less expenditure of time and effort. A variant of CEA with a lower molecular weight was also identified in both preparations.

Antibodies, Monoclonal↗
PubMed1986

In vivo studies on the uptake of radiolabelled antibodies by colorectal and gastric carcinoma xenografts.

A number of criteria have been investigated to try to improve the uptake of radiolabelled antibodies by colorectal carcinoma xenografts. The in vivo behaviour of four antibodies was compared and found to vary. Two antibodies, 11-285-14 and 14-95-55, demonstrated specific uptake by the tumours. 11-357-5 was lost from the tumour after 72 h and the fourth antibody could not be iodinated without loss of activity. Neither increased time nor increased dose were shown to increase the uptake of antibody by tumours although the clearance of antibody from blood was shown to be more rapid than from tumour resulting in clearer backgrounds. Increased tumour:blood ratios were demonstrated by particular combinations of antibodies but the extent to which this occurred varied with the epitopes recognised. High carcinoembryonic antigen expressing xenografts did not show significantly higher uptake of antibody. This was shown to be due to the smaller size of these tumours and associated decreased vascularity.

Animals↗
PubMed1986

Demonstration of carcinoembryonic antigen (CEA) expression in normal, chronically inflamed, and malignant pancreatic tissue by immunohistochemistry.

The expression of carcinoembryonic antigen (CEA) was evaluated by immunoperoxidase staining with two anti-CEA monoclonal antibodies in normal, chronically inflamed, and malignant pancreatic tissue. Positive staining was not observed in normal specimens. In pancreatic cancer the expression of CEA was related to the degree of differentiation of the tumour. Positive staining was also observed in chronic pancreatitis.

Adenocarcinoma↗
PubMed1984

Carcinoembryonic antigen (CEA) expression and heterogeneity in primary and autologous metastatic gastric tumours demonstrated by a monoclonal antibody.

The expression of carcinoembryonic antigen (CEA) in gastric malignancies has been assessed using a monoclonal antibody in an immunoperoxidase technique. Of 119 primary tumours examined, 92% reacted with the antibody. Metastases were available for 81 of the patients and 83% were CEA positive. A noteworthy observation was the detection of malignant cells in the lymph nodes of two patients, as a result of the presence of CEA, who were originally reported to be free of metastases. Of those patients whose primary tumours expressed CEA, 86% had at least one CEA positive metastasis. Two or more metastases were available from 60 of the patients and in 20% the secondaries were a mixture of positive and negative for CEA. Consequently, the CEA status of a single lesion does not enable confident prediction of expression in other metastases. In addition to variation between multiple lesions removed from the same patient phenotypic diversity of expression was observed between tumour cells of a given mass. Such distribution of the CEA detected by this monoclonal antibody may impose certain restrictions on its application. However, the high frequency of expression by gastric cancers indicate that it is a potentially useful antigen as a target for radiolocalisation or therapeutic agents.

Antibodies, Monoclonal↗
PubMed1984

Secretion of inducible proteinase by pathogenic Candida species.

The ability of three isolates each of seven pathogenic Candida species to grow in a liquid medium containing bovine serum albumin (BSA) as a nitrogen source was determined. All three strains of C. albicans, two strains of C. guilliermondii and one strain of C. tropicalis grew well. At any time proteinase activity was detected in the culture filtrates of only the most virulent species--C. albicans, C. tropicalis and C. parapsilosis and this observation was related to complete hydrolysis of BSA. Serologically, cross reactions were demonstrated between anti-proteinase antiserum and C. albicans and C. tropicalis culture filtrates. These results further emphasise the role of the inducible proteinase of Candida in the pathogenesis of candidosis.

Candida↗
PubMed1983

Virulence for mice of a proteinase-secreting strain of Candida albicans and a proteinase-deficient mutant.

A proteinase-deficient mutant of Candida albicans, M12, was produced by nitrosoguanidine mutagenesis of a proteinase-producing strain, ATCC 28366. The mutant was phenotypically identical to its parent in nearly all biochemical and morphological characteristics except proteinase production. The mutant was considerably less lethal than the parent when inoculated intravenously into mice and lower counts of C. albicans were recovered from the organs of mice infected with the mutant. Both strains were phagocytosed and killed to a similar extent by human and murine polymorphonuclear leukocytes when the yeasts were grown in a medium that did not induce proteinase production. However, in a proteinase-inducing medium, ATCC 28366 was phagocytosed and killed less well than M12. These results indicate that proteinase secretion by C. albicans is one factor determining the virulence of the species, but that other virulence factors are also involved in the pathogenesis of systemic candidosis.

Animals↗
PubMed1980

Purified Candida albicans proteinase in the serological diagnosis of systemic candidosis.

An inducible, exocellular proteinase enzyme, purified from culture filtrates of Candida albicans, was tested as an antigen for the detection of serum anti-Candida precipitins. The purified proteinase was a more specific antigen for the serological diagnosis of systemic candidosis than traditional cytoplasmic extracts of the fungus. Precipitin titers to purified proteinase exceeded 1:4 in 75% of serum samples from 12 patients with confirmed systemic Candida infection, in 23% of serum samples from 22 patients positive for Candida anticytoplasm antibodies but without corroborative diagnostic evidence of systemic candidosis, and in none of 28 serum samples from patients without either candidosis or anticytoplasm antibodies.

Antigens, Fungal↗