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S Edwards

Publications and source records attributed to S Edwards.

At least 217 records · Page 12Linked to original sources
PubMed1987

Mapping of monoclonal antibody-defined epitopes associated with carcinoembryonic antigen, CEA.

Six immunoglobulin G monoclonal antibodies reactive with carcinoembryonic antigen (CEA) were evaluated with respect to parameters implicated in their potential diagnostic application and use as tumor targeting agents for cytotoxic drugs or plant or bacterial toxins. Antibody reactivity with surface antigens of the MKN-45 gastric tumor cell line was demonstrated by flow cytofluorimetry. In a subcellular membrane binding assay, each antibody reacted preferentially with membranes isolated from colorectal tumor tissue in comparison with their reaction with membranes from adjacent, apparently normal colonic mucosa. Three of the antibodies (NCRC-23, C228, and 11.285.14) reacted specifically with CEA with little or no reaction with the cross-reacting antigen, NCA. The remaining three antibodies (C24, C161, and C198) were reactive with both CEA and NCA. Analysis of the epitopes defined by these antibodies was performed by competitive binding inhibition assays evaluating the capacity of unlabeled antibodies to compete with 125I-labeled antibodies in their binding to CEA. In addition, double determinant or 'sandwich' radioimmunoassays were employed to examine the coexpression of epitopes on CEA molecules. These studies permitted an epitope map to be constructed which describes the coincidence, overlapping, or independent expression of both CEA specific epitopes and epitopes shared between CEA and NCA. The map may be employed for the selection of antibodies for diagnostic and therapeutic use.

Antibodies, Monoclonal↗
PubMed1987

Identification of a monoclonal antibody-defined breast carcinoma antigen in body fluids.

The monoclonal antibody NCRC-11 defines antigens associated with secretory glandular epithelia as well as most epithelial malignancies. These components have been identified in, and isolated from, normal body fluids including urine and skim milk. The immunoadsorbent purified antigens from urine and milk were very similar to those purified from breast and ovarian carcinomas; by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE) and immunoblotting, NCRC-11 antibody-binding antigens from all sources were of high apparent molecular weight (greater than 400 kD) with the major component(s) present as a single band or a doublet. Also, by analysing epitope profiles, all purified antigen preparations were shown to react in a characteristic manner with a panel of monoclonal antibodies which were originally produced against human milk products or materials from tumours. Since it was shown that NCRC-11 antigens were released from tissues in a soluble form, the possibility that these antigens might represent a diagnostic marker for breast cancer was evaluated. The findings obtained indicated that NCRC-11 antigens were elevated in the serum of advanced breast cancer patients in comparison to healthy control females, so that access to the circulation was available to these products released from the tumour but not to those released from normal epithelia.

Aged↗
PubMed1987

Highly sensitive antigen detection procedures for the diagnosis of infectious bovine rhinotracheitis: amplified ELISA and reverse passive haemagglutination.

The sensitivity of an enzyme-linked immunosorbent assay (ELISA) for the detection of bovid herpesvirus 1 antigen was increased by up to 50-fold using the biotin-avidin interaction to amplify the reaction, when compared with a simple sandwich ELISA. An alternative immunoassay, reverse passive haemagglutination (RPHA), had a similar sensitivity to the amplified ELISA, and was technically simpler to perform. Both the amplified ELISA and the RPHA could detect viral antigen in the nasal secretions of calves undergoing experimental primary infection with the virus from Day 3 to Day 7 after inoculation. Neither assay was as sensitive as virus isolation in cell culture and they failed to detect antigen in virus-positive samples from the calves from 8 days after inoculation, and from vaccinated calves undergoing challenge infection.

Animals↗
PubMed1987

A comparison of three rapid diagnostic methods for the detection of rotavirus infection in calves.

Three techniques for the detection of rotavirus in faecal samples from calves with neonatal gastroenteritis were compared. A preliminary study indicated that reverse passive haemagglutination (RPHA) was at least as sensitive as the enzyme-linked immunosorbent assay (ELISA). These two immunoassays were compared with the detection of viral RNA by polyacrylamide gel electrophoresis (PAGE) on 209 field samples. Of the 77 samples in which at least one test gave a positive result, 69 were positive by both RPHA and PAGE, but only 49 were also positive by ELISA, indicating a lower sensitivity for the latter test. The overall agreement between RPHA and PAGE was 96%. The reasons for the discrepancies between the tests are discussed.

Animals↗
PubMed1987

The response to DNA damage induced by 4-nitroquinoline-1-oxide or its 3-methyl derivative in xeroderma pigmentosum fibroblasts belonging to different complementation groups: evidence for different epistasis groups involved in the repair of large adducts in human DNA.

The data in this paper show that when the inhibition of growth is measured, xeroderma pigmentosum (XP) complementation groups A, G and D are very sensitive to 4-nitroquinoline-1-oxide (4NQO), whereas only XP groups G and D are very sensitive to 3-methyl-4NQO (3me4NQO). Cells belonging to XP-C group are not particularly sensitive to either agent. Thus there are different epistasis groups for the excision repair of DNA adducts induced by these agents as opposed to the repair of u.v. damage. DNA polymerase alpha is involved in the repair of 4NQO-induced lesions because aphidicolin blocks their repair. XP cells from all the above groups are defective to some extent in this repair. The degree of repair defectiveness follows that seen after u.v., with even the XP-C cell line used having reduced repair (despite the fact that the inhibition of growth by 4NQO in this cell line was not markedly different from normal). Aphidicolin did not induce breaks in the normal or XP cell lines exposed to 3me4NQO, thus the repair of lesions induced by 3me4NQO does not involve DNA polymerase alpha in any of the cell lines. Finally, catalase reduces the alkaline labile lesions induced by 4NQO, but not 3me4NQO, suggesting the latter agent does not induce substantial amounts of DNA damage by the generation of radicals.

4-Nitroquinoline-1-oxide↗
PubMed1987

Intrusive unwanted thoughts: a two-stage model of control.

It was proposed that the greater time taken to dismiss intrusive compared with neutral thoughts is better explained in terms of a decreased ability to disattend to the intrusive thought than a decreased ability to access a more pleasant replacement thought. A study of 43 subjects with 'normal obsessions' using a methodology that controlled the valence and content of replacement thoughts provided support for this disattention hypothesis.

Adolescent↗
PubMed1987

Scintigraphy and treatment of medullary carcinoma of the thyroid with iodine-131 metaiodobenzylguanidine.

We report our experience using [131I]metaiodobenzylguanidine (MIBG) to image nine patients with proven medullary carcinoma of the thyroid (MCT). Positive uptake was seen in four patients, equivocal uptake in one patient, and no uptake in four patients. Data is presented to demonstrate the pharmacokinetics of [131I]MIBG in three of the patients studied. Two patients, with diarrhea and severe pain from known bone metastases and positive uptake on [131I]MIBG diagnostic scanning, subsequently received therapeutic doses of [131I]MIBG, with marked improvement in both pain and diarrhea, but no evidence of significant biochemical response. Iodine-131 MIBG uptake in patients with MCT is variable, and gives a higher false-negative rate than is found when using [131I]MIBG to image other neuroectodermally derived tumors. The therapeutic potential of [131I]MIBG in patients with MCT warrants further evaluation, in view of the symptomatic relief experienced following therapy doses in two patients with extensive disease.

3-Iodobenzylguanidine↗
PubMed1986

Application of a subcellular membrane-antibody binding assay for the analysis of antigen expression in human tumours.

A micro-radioisotopic antiglobulin assay has been employed to determine the binding of monoclonal antibodies to subcellular membranes adsorbed to the wells of Terasaki Microtest Plates. A panel of 15 monoclonal antibodies was tested against 22 membrane preparations isolated from normal and malignant colo-rectal, breast and lung tissues. The assay provided an objective evaluation of antibody reactivity permitting the expression of major antigens in samples from individual surgical specimens to be defined.

Antibodies, Monoclonal↗
PubMed1986

Evidence for an immunocompromising effect of bovine pestivirus on bovid herpesvirus 1 vaccination.

Five calves were given live intranasal vaccine against bovid herpesvirus 1 (BHV1) two days after intranasal inoculation of bovine pestivirus (BVDV). Another 5 were vaccinated in the absence of BVDV. Control unvaccinated groups were also maintained. All calves were challenged with virulent BHV1. The unvaccinated calves developed signs of infectious bovine rhinotracheitis (IBR) and both vaccinated groups showed a similar degree of clinical protection from IBR. Those given BVDV before vaccination shed up to 140 times more BHV1 (P less than 0.01) in the nasal mucus following challenge than those which had received BHV1 vaccine alone. The epidemiological significance of this is discussed.

Animals↗
PubMed1986

Association of the Y hapten with glycoproteins, glycolipids and carcinoembryonic antigen in colorectal carcinoma.

The expression of the Y hapten (Fuc alpha 1----2Gal beta 1----4[Fuc alpha 1----3]GlcNAc-) defined by the monoclonal antibody C14/1/46/10 (abbreviated to C14), is frequently elevated in colo-rectal tumours in comparison to adjacent, apparently normal tissues. This determinant was shown to be expressed upon glycoproteins of approximately 200 kDa, which were isolated by immunoadsorbent chromatography from detergent-solubilized subcellular membranes and cytosol from colo-rectal carcinoma. In addition, the Y hapten was expressed upon purified carcinoembryonic antigen (CEA, 180 kDa). However, monoclonal antibodies specifically reactive with CEA or cross-reactive with CEA and NCA-1 (normal cross-reacting antigen) failed to react with the C14 defined antigens of 200 kDa. Further diversity in the expression of molecules bearing the Y hapten was established following its identification in the glycolipid fraction of colo-rectal carcinoma.

Antibodies, Monoclonal↗
PubMed1986

Epitope analysis of monoclonal antibody NCRC-11 defined antigen isolated from human ovarian and breast carcinomas.

NCRC-11 is an IgM monoclonal antibody which defines an antigen found in most epithelial malignancies. The antigen has previously been shown to be a high mol. wt. glycoprotein (greater than 400,000) and in this study, antigen preparations were isolated by immunoadsorbent chromatography from ovarian mucinous and ovarian serous cyst adenocarcinoma and from breast carcinoma. Other monoclonal antibodies, against products in normal human milk, and antibodies of the Ca series (Bramwell et al., 1985) reacted with all three antigen preparations. Tests involving epitope mapping were performed to probe the relationships of the various epitopes to that defined by the NCRC-11 antibody, and, of note, the three antigen preparations from different tumour sources were remarkably similar with respect to their relative levels of epitope expression and to their topographical distribution of epitopes. The major differences in epitope expression could be attributed to the degree of sialylation in the three antigens. The antigens from ovarian tumours expressed I(Ma) blood group determinants (defined by the antibody LICR-LON-M18) which were partially masked by sialic acid. With NCRC-11 defined antigen from breast carcinoma, this determinant was totally masked by sialic acid although neuraminidase treatment clearly exposed epitopes reactive with M18 antibodies.

Antibodies, Monoclonal↗
PubMed1986

DNA ethylations induced by ethylnitrosourea in the wild type, cdc4 and cdc7 strains of Saccharomyces cerevisiae.

The experiments reported here have investigated the induction of ethylations to DNA in yeast cells exposed to the chemical mutagen ethylnitrosourea. A similar level of alkylation was seen at the N7 and O6 of guanine and at the N3 of adenine in either log phase cells or in temperature-sensitive cdc4 and cdc7 cells growth arrested at their specific G1 positions. Hence the changes in chromosome structure associated with the above cdc phenotypes do not modify the amount of DNA damage induced by ethylnitrosourea.

DNA Damage↗
PubMed1986

The induction of DNA adducts in mammalian cells exposed to 1-nitropyrene and its nitro-reduced derivatives.

1-Nitropyrene, 1-nitrosopyrene and 1-aminopyrene were investigated for their ability to induce covalently bound DNA adducts in calf thymus DNA and Chinese hamster lung fibroblasts. Xanthine oxidase catalysed the induction of one major and one minor DNA adduct in 1-nitropyrene- or 1-nitrosopyrene-treated calf thymus DNA, whilst 1-aminopyrene was inactive. These compounds did not form detectable DNA adducts in the absence of xanthine oxidase. The major DNA adduct produced by 1-nitropyrene and 1-nitrosopyrene in calf thymus DNA co-migrated on h.p.l.c., and the structure was consistent with that previously described by others as N-(deoxyguanosin-8-yl)-1-aminopyrene. The compounds were investigated for their ability to form DNA adducts in Chinese hamster lung fibroblasts. 1-Nitropyrene (5.2 pmol/mg DNA/h) and 1-nitrosopyrene (129 pmol/mg DNA/h) formed a single DNA adduct in Chinese hamster lung cells which co-eluted on h.p.l.c. with the C-8 deoxyguanosine adduct isolated from 1-nitropyrene-treated calf thymus DNA. 1-Nitrosopyrene was the most efficient compound investigated for the production of the C-8 guanine adducts. In contrast, 1-aminopyrene (14.7 pmol/mg DNA/h) induced the formation of a DNA adduct which did not co-elute with the C-8 guanine adduct. The data presented here suggest that 1-nitropyrene and 1-aminopyrene are metabolized to reactive intermediates which form different DNA adducts in Chinese hamster lung fibroblasts.

Animals↗