Life Sciences Research for Lifelong Health

Publications

The Babraham Institute Publications database contains details of all publications resulting from our research groups and scientific services.

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Title / Authors / Details Open Access Download

CD4+ T-cell clones from autoimmune thyroid tissue cannot be classified according to their lymphokine production.
Grubeck-Loebenstein B, Turner M, Pirich K, Kassal H, Londei M, Waldhäusl W, Feldmann M

In order to define whether CD4+ T cells from autoimmune and non-autoimmune thyroid tissue could be classified according to their mediator production, lymphokine production was studied in 63 thyroid-derived CD4+ T-cell clones from four patients with Graves' disease, one with Hashimoto's thyroiditis, and one with non-toxic goitre (9-12 clones per patient). The production of interleukin 2 (IL-2), gamma interferon (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), lymphotoxin (LT), interleukin 6 (IL-6) and transforming growth factor beta (TGF-beta) was assessed at the mRNA level by slot-blot analysis in unstimulated clones as well as after activation with monoclonal anti-CD3 (OKT3) and IL-2. No lymphokine production was found in unstimulated clones, whereas 56% of the clones produced all six lymphokines simultaneously after stimulation. In the remaining 44% usually not more than one lymphokine was missing from the complete panel. Lymphokine mRNA concentrations varied between different clones and different patients, but, in this small sample, not between the diseases from which the clones were originated. There was a significant correlation between IL-6, LT, and IL-2 mRNA levels and T-cell helper function, which was estimated by the stimulation of thyroid microsomal autoantibody production using autologous peripheral B cells. TGF-beta and IFN-gamma mRNA expression was unrelated to T-cell help. The results demonstrate that intrathyroid T cells from autoimmune and non-autoimmune thyroid disorders cannot be classified according to their lymphokine production, unlike some results with in vitro-induced mouse T-cell clones, where two populations, Th1 and Th2, have been described. Single T cells are capable of producing a whole panel of lymphokines and thus are capable of triggering a multitude of different processes.

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Scandinavian journal of immunology, 32, 0300-9475, 433-40, 1990

PMID: 1980155


Structure of a mannan isolated from the lipopolysaccharide of the reference strain (S3255) for a new serogroup of Serratia marcescens.
Oxley D,Wilkinson SG

Both a neutral and an acidic polymer have been isolated from a lipopolysaccharide extract of Serratia marcescens strain S3255. The neutral polymer is a linear mannan with the repeating unit shown. The same repeating unit has been described for the O-specific polymers from Escherichia coli O8 and Klebsiella O5.

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Carbohydrate research, 212, 0008-6215, 213-7, 1991

PMID: 1959117


Induction of the interleukin 1 receptor antagonist protein by transforming growth factor-beta.
Turner M, Chantry D, Katsikis P, Berger A, Brennan FM, Feldmann M

Transforming growth factor-beta 1 (TGF-beta 1) mediates many immunosuppressive effects on immune cells and can inhibit the production of tumor necrosis factor and interleukin 1 (IL 1). However, TGF-beta 1 can stimulate the production of IL 6 and platelet-derived growth factor, indicating that TGF-beta 1 initiates complex effects on the production of cytokines. In this report we show that treatment of peripheral blood monocytes with TGF-beta 1 leads to the induction of a recently described IL 1 receptor antagonist protein (IRAP). The effect of TGF-beta 1 was both dose and time dependent. TGF-beta 1 induced de novo synthesis of IRAP, as Northern blotting experiments indicated a rapid and transient induction of the mRNA encoding IRAP. The induction of IRAP suggests a potential mechanism by which some of the inhibitory effects of TGF-beta 1 are mediated.

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European journal of immunology, 21, 0014-2980, 1635-9, 1991

PMID: 1829411


Open Access

Structure of an acidic glycan present in the lipopolysaccharide extract from the reference strain for Serratia marcescens serogroup O18.
Oxley D,Wilkinson SG

The lipopolysaccharide extract from the cell wall of the reference strain for Serratia marcescens serogroup O18 contained, in addition to a neutral glycan characterised previously, an acidic glycan. Acidity was contributed both by D-glucuronic acid and by 4-O-[(R)-1-carboxyethyl]-D-glucose (4-O-Lac-D-Glc). By using n.m.r. spectroscopy, methylation analysis, and chemical degradations, the repeating unit of the acidic glycan was identified as a branched hexasaccharide having the structure shown; an O-acetyl group also present was not located. The glycan is believed to define the O18 serogroup, but is probably not an integral component of the lipopolysaccharide. [formula: see text].

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Carbohydrate research, 215, 0008-6215, 293-301, 1991

PMID: 1794127


Monoclonal antibodies to idiotype inhibit in vitro growth of human B-cell lymphomas.
van Endert PM, Heilig B, Hämmerling GJ, Moldenhauer G

The effect of monoclonal antibodies (MoAbs) recognizing idiotype, IgM heavy chain, and IgD heavy chain on the in vitro DNA synthesis of five randomly selected leukemic human low-malignancy B-cell lymphomas was investigated. In three lymphomas of different histologic subtype, low concentrations of anti-idiotypic (anti-Id) MoAb completely inhibited spontaneous 3H-thymidine uptake of T-cell-- and monocyte-depleted tumor cells, whereas two other tumors were not affected. Maximal inhibition of DNA synthesis was achieved at MoAb concentrations ranging from 0.5 to 250 micrograms/mL and required crosslinking by bivalent antibody but not Fc-mediated effects. While two anti-IgM MoAbs were similarly efficient as anti-Id MoAb in inhibition of DNA synthesis, two anti-IgD MoAbs had no effect. Thus, surface IgD molecules seemed to be neither able to deliver inhibitory signals themselves nor to antagonize IgM-mediated signals when simultaneously crosslinked by anti-Id MoAb. Leukocyte differentiation antigen expression, IgM density, and IgM/IgD ratio on the surface of lymphoma cells did not distinguish between sensitive and resistant tumors. In vitro tumor cell survival was differently affected by prolonged incubation with anti-Id antibody. In a centrocytic lymphoma and an immunocytoma, but not in a chronic lymphocytic leukemia, suppression of 3H-thymidine uptake persisted after removal of MoAb and tumor cell viability decreased during prolonged incubation with anti-Id MoAb. These results suggest that direct inhibitory signaling via surface IgM may contribute to anti-Id MoAb-mediated tumor regression in certain human B-cell lymphomas.

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Blood, 79, 0006-4971, 129-37, 1992

PMID: 1728304


Open Access

Structure of the 021 antigen from Serratia marcescens.
Oxley D,Wilkinson SG

Lipopolysaccharide was isolated from both phases of an aqueous-phenol extraction of defatted cell walls from the reference strain for Serratia marcescens serogroup 021. The product from the aqueous phase was of the R type, lacking a polymeric side-chain. The polymeric fraction of the lipopolysaccharide from the phenolic phase (the 021 antigen) had a disaccharide repeating-unit with the following structure: ----4)-alpha-D-Glcp-(1----4)-beta-D-ManpNAc-(1----.

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Carbohydrate research, 212, 0008-6215, 187-92, 1991

PMID: 1720344


Structure of a glucorhamnan from the lipopolysaccharide of Serratia marcescens strain S1254.
Oxley D,Wilkinson SG

Carbohydrate research, 209, 0008-6215, 319-22, 1991

PMID: 1709820


Structure of the putative O23 antigen of Serratia marcescens.
Oxley D,Wilkinson SG

A neutral glycan containing L-rhamnose and 2-acetamido-2-deoxy-D-galactose is one of two polymers present in the lipopolysaccharide extract from the reference strain for Serratia marcescens serogroup O23. The glycan, which has the disaccharide repeating-unit shown, shares structural features with polymers from several other O serogroups. ----4)-alpha-L-Rhap-(1----4)-beta-D-GalpNAc-(1----.

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Carbohydrate research, 196, 0008-6215, 127-31, 1990

PMID: 1693310


Structure of an acidic glycan from the reference strain for Serratia marcescens serogroup O22.
Oxley D,Wilkinson SG

In addition to a neutral glycan, lipopolysaccharide extracts from the reference strain for Serratia marcescens serogroup O22 contain an acidic polymer which probably defines the serogroup and is of microcapsular origin. The polymer is doubly branched with a heptasaccharide repeating unit and a galactan backbone. By means of spectroscopic and degradative studies, the structure of the repeating unit was established as that shown. [formula: see text]

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Carbohydrate research, 231, 0008-6215, 237-48, 1992

PMID: 1394317


Structure of a neutral glycan from the lipopolysaccharides of reference strains for Serratia marcescens serogroups O2 and O3.
Oxley D,Wilkinson SG

Serogroups O2 and O3 of Serratia marcescens are differentiated by acidic glycans present in the aqueous phase when lipopolysaccharides are extracted from the reference strains by the aqueous-phenol method. The phenolic phases of these extracts from both strains also contain lipopolysaccharides, from which the same neutral glycan is released on milk acid hydrolysis. The neutral glycan has the disaccharide repeating-unit shown, and accounts for the cross-reactions between the two serogroups and also with serogroup O21: --> 4)-alpha-D-GlcpNAc-(1-->4)-beta-D-ManpNAc-(1--.

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FEMS microbiology letters, 78, 0378-1097, 209-12, 1992

PMID: 1283379


First cell fate decisions in early development – towards establishment of the trophoblast lineage
M Hemberger and W Dean

The Guide of Investigations of Mouse Pregnancy, , , , 2013


Simulating the Bacterial Chemotaxis Pathway at High Spatio-temporal Detail
Sewitz S and Lipkow K

We have used the Smoldyn software to create spatially detailed models of the Escherichia coli chemotaxis pathway. With it we can follow signalling reactions at high spatio-temporal resolution, observe the formation of gradients of phospho-proteins as well as total protein and analyse the effects of macromolecular crowding on signalling. It has enabled us to propose new regulatory elements of the signalling pathway, which are mediated through the dynamic localisation and activity of the CheZ phosphatase. We used the Smoldyn software to model quantitative fluorescent microscopy data and to determine diffusion coefficients and binding affinities. We can reliably gain information obtained under conditions with high levels of experimental noise. Smoldyn can accommodate various cellular architectures, and we show that cell shape becomes an integral part of the signalling process.

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Current Chemical Biology, 7, 3, 214 - 223, 2013