PubMed Health⌕ Search

Biomedical subjects

C Turberville

Publications and source records attributed to C Turberville.

16 recordsLinked to original sources

Cell membrane glycoproteins of human mast cells: a biochemical comparison with basophils.

The relationship of mast cells (MCs) to other blood leucocytes, and to basophils in particular, is unclear. The relative distribution and abundance of cell surface glycoproteins of normal and neoplastic blood cells has been established as providing a "fingerprint" allowing assignment to a particular hemopoietic cell lineage. We have examined the major labeled glycoproteins of mast cells, basophils, HL-60 cells (granulocytic), and U937 cells (monocytic), after cell surface tritiation by the periodate-borohydride technique. Mast cells have a characteristic glycoprotein profile, different from that of basophils and other leukocytes; a major feature is the lack of the gp105-115 molecular weight band common to all other white blood cells. The data suggest that the tissue mast cell is more distantly related to other hemopoietic cells than has been previously recognized.

Basophils↗

Human mast cells detected by monoclonal antibodies.

We report the establishment of seven mouse-mouse hybridoma cell lines secreting monoclonal antibodies with specificity for granule components of all human mast cells. Reactivity is directed against a molecule which is also found intracytoplasmically in human mature small intestinal enterocytes, liver parenchymal cells, and kidney proximal tubule epithelial cells. No reactivity of these antibodies was found with any other human or animal cell type examined. In particular, the antibodies did not react with basophils or other haemopoietic cell types. This study shows the potential of specific monoclonal antibodies as a tool for identifying and enumerating infiltrating mast cells in tissues. Such antibodies should be of value in investigations into the role of the mast cell in immunological reactions and hypersensitivity diseases.

Animals↗

Biochemically-defined differentiation markers on human early haemopoietic (K562) cells.

Both haemin, contrary to a previous report, and the tumor promoter TPA induce pronounced changes in surface protein patterns of human erythroleukaemic (K562) cells. Three major surface proteins are down-regulated by both inducers. These are not merely growth-related proteins and therefore represent candidate markers for an early stage of haemopoietic differentiation.

Cell Differentiation↗

Multiple differentiation programs in K562 erythroleukemia cells and their regulation.

The chronic myeloid leukemia-derived cell line K562 expresses, in its uninduced state, notable erythroid features. However, in addition to the presence of well-characterized "erythroid-specific" molecules, such as hemoglobin and glycophorin A, there is increasing evidence of both granulopoietic and megakaryocytic differentiation in this cell line. In this chapter we have further characterized erythroid and nonerythroid features in order to investigate the range of differentiation programs expressed by uninduced K562 cells. Also we have extended these observations by attempting to manipulate the expression of the different lineage-specific components of the phenotype of the K562 cell line in induction experiments. The aim of these studies was to attempt to determine the extent and significance of multipotentiality in K562. The relationship of our findings on the phenotype of K562 to the nature of multipotent hemopoietic stem cells and their differentiated progeny in normal and malignant hemopoiesis is discussed.

Animals↗

The monitoring role of plasma CEA alone and in association with other tumor markers in colorectal and mammary carcinoma.

During the past decade, evidence has accumulated to show that most, if not all, human tumors produce a variety of different factors which, if they pass into the blood and/or urine, may serve as tumor index substances (tumor markers).7 Tumor markers may either be: 1) tumor-derived--i.e., produced by the tumor itself, or 2) tumor-associated--i.e., produced by other tissues in response to the presence of the tumor and its local or distant effects on that tissue. Examples of this latter category include the changes in urinary hydroxyproline output in patients with bone metastases or the altered levels of serum acute phase proteins in neoplasia in general.7 Tumor-derived markers may be produced by either the tumor cell population itself, e.g., CEA, alpha-fetoprotein (AFP), and other oncofetal antigens, inappropriate hormones such as ACTH etc., or by their supporting framework (stroma), e.g., the osteolysins of human breast cancer.3

Breast Neoplasms↗

Blood-group precursors and cancer-related antigens.

Glycoprotein extracts from colonic tumours were tested for blood-group precursor-like activities using human anti-I and anti-i cold agglutinins as reagents. Substantial activity was detected in the high-molecular-weight fractions of two metastatic tumours. A carcinoembryonic antigen (C.E.A.) fraction from one of these tumours was also active. The C.E.A. and the precursor-like activities were located on separate molecules. These data indicate that the levels of precursor-like antigens in entodermal tumours and their possible diagnostic value warrant detailed investigation.

Antigens, Neoplasm↗

First British standard for carcinoembryonic antigen (CEA).

In 1974, the National Institute for Biological Standards and Control (NIBSC) established the first British Standard for carcinoembryonic antigen (CEA) for use in comparative quantitative assays. The Standard, which was prepared for material processed by the Chester Beatty Research Institute, is in the form of a freeze-dried powder, sealed in all glass ampoules code labelled 73/601 and containing pure dry nitrogen. For practical purposes, each ampoule contains 100 units of CEA activity.

Amino Acids↗

Human tumour-associated and tumour-specific antigens: some concepts in relation to clinical oncology.

The concept of tumour-specific antigens is constantly undergoing reappraisal with the development of more sensitive methods for their detection. This has resulted in the finding that the many 'new' antigens produced by human tumours or materials immunologically closely related to them are also present in non-neoplastic tissues, albeit in small amounts. However, other antigens still appear to exist almost entirely in or on tumour cells so that the antigens of human tumours may be subdivided into either tumour-associated macromolecules or tumour-specific antigens. The elucidation of the chemical nature of the tumour-specific antigens may result in important advances in cancer diagnosis and therapy. As many are organ specific, it should be possible to evolve test systems which will enable tumours to be diagnosed and located before they become apparent clinically. On the other hand the tumour-associated macromolecules, of which the oncofetal antigens are the principal examples, are found in elevated amounts in some non-neoplastic disorders. It is now clear that serial estimation of the levels of these macromolecules is of considerably more diagnostic value than single random measurements. Current work is establishing their value in the detection of recurrent and metastatic tumours before they become apparent by other methods, which is probably their most important role, and also their value as aids to monitor therapeutic efficacy. The future use of both types of antigen may unfold a new era in cancer detection and therapy but many basic chemical and immunological studies are needed before their clinical use can be fully defined.

Antigens, Neoplasm↗

Immunological study of carcinoembryonic antigen (CEA) and a related glycoprotein.

A comparison has been made of the immunological properties of CEA (carcinoembryonic antigen) and another perchloric acid-soluble macromolecule which occurs in colonic and certain other carcinomata and which is here termed CEX. By using a variety of antisera it was shown that the two substances share common antigenic groups as well as having characteristic ones of their own. These latter groups have enabled the preparation of (a) antisera which give a gel diffusion line only with CEA and (b) and antiserum which gives a line only with CEX. No immunological difference could be found between CEX and the NGP of Mach or the NCA of von Kleist and Burtin. CEX was found in foetal gut, in plasma and associated with CEA in virtually all the tissues and fluids in which the latter occurs; the two appear to go hand-in-hand and no proof was found that CEX is either less or more cancer specific than CEA-it is merely found in greater quantity; neither substance showed absolute cancer specificity. The usefulness of a radioimmunoassay for CEX is discussed, and also the possibility of interference by CEX in the radioimmunoassay for CEA. Evidence of two molecular species of CEA has been found.

Absorption↗

Role of plasma carcinoembryonic antigen in diagnosis of gastrointestinal, mammary, and bronchial carcinoma.

Our studies have confirmed that raised plasma levels of carcinoembryonic antigen (C.E.A.) occur with many but not all malignant tumours, particularly those of the gastrointestinal tract, breast, and bronchus. However, the incidence of raised values may reach 30% in diseases associated with inflammation or regeneration or both. Consequently, it cannot serve yet as a routine screening test for cancer. Effective surgical therapy results in high plasma C.E.A. levels returning to normal. Subsequent rises appear to develop with tumour recurrence or spread. At present the most useful role for C.E.A. seems to be in monitoring patients during the post-therapeutic followup period. Further basic work is required before C.E.A. can become of routine medical value.

Adult↗

Methylation of nuclear proteins by dimethylnitrosamine and by methionine in the rat in vivo.

1. The incorporation of methyl groups into histones from dimethylnitrosamine and from methionine was studied by injection of the labelled compounds, isolation of rat liver and kidney histones, and analysis of hydrolysates by column chromatography. 2. Labelled methionine gave rise to labelled in-N-methyl-lysine, di-in-N-methyl-lysine and an amino acid presumed to be omega-N-methyl-arginine. 3. Administration of labelled dimethylnitrosamine gave rise to labelled S-methylcysteine, 1-methylhistidine, 3-methylhistidine and in-N-methyl-lysine derived from the alkylating metabolite of dimethylnitrosamine. In addition, labelled formaldehyde released by metabolism of dimethylnitrosamine leads to the formation of labelled S-adenosylmethionine, and hence to labelling of in-N-methyl-lysine, di-in-N-methyl-lysine and omega-N-methylarginine by enzymic methylation. 4. The formation of in-N-methyl-lysine by alkylation of liver histones was confirmed by using doubly labelled dimethylnitrosamine to discriminate between direct chemical alkylation and enzymic methylation via S-adenosylmethionine. These experiments also suggested the possibility that methionine residues in the histones were alkylated to give methylmethionine sulphonium residues. 5. The extent of alkylation of liver histones was maximal at about 5h after dosing and declined between 5 and 24h. The methylated amino acids resulting from direct chemical alkylation were preferentially lost: this is ascribed to necrosis of the more highly alkylated cells. 6. Liver histones were about four times as alkylated as kidney histones; the extent of alkylation of liver histones was similar to that of liver total nuclear proteins. 7. Methyl methanesulphonate (120mg/kg) alkylated liver histones to a greater extent than did dimethylnitrosamine. Diethylnitrosamine also alkylated liver histones. 8. The results are discussed with regard to the possible effects of alkylation on histone function, and the possible role of histone alkylation in carcinogenesis by the three compounds.

Alkylation↗