Searchable abstracts of presentations at key conferences in endocrinology

ea0011s11 | Thyroid and the heart | ECE2006

Cardiac repercussions of thyroid hormones

Franklyn JA

The cardiovascular symptoms and signs of overt thyrotoxicosis are well known. These symptoms and signs may persist even after successful restoration of euthyroidism. Long-term, overt hyperthyroidism is associated with increased vascular mortality, from both cardiovascular and cerebrovascular causes, even in patients treated in the last 20 years. This mortality may particularly reflect an effect of thyroid hormone excess on cardiac rhythm, especially risk of atrial fibrillation...

ea0011p492 | Endocrine tumours and neoplasia | ECE2006

PTTG binding factor (PBF) can transform cells independently of interaction with PTTG

Stratford AL , Boelaert K , Kim DS , Franklyn JA , McCabe CJ

We have previously shown PTTG and PBF to be over-expressed in differentiated thyroid cancer and to be prognostic indicators for recurrence. Subsequently we reported PBF to be a transforming gene in vitro and tumourigenic in vivo. Since over-expression of PTTG results in the same findings, we examined whether PBF-induced tumourigenesis was an independent effect, or else a result of increased PTTG activity. Two HA-tagged mutants of PBF were generated, firstly subst...

ea0011p880 | Thyroid | ECE2006

Do SNPs within the PTPN22 gene contribute to autoimmune disease via different mechanisms?

Heward J , Simmonds M , Franklyn JA , Gough SC

Graves’ disease (GD) is an autoimmune disorder of the thyroid gland. Autoimmune diseases cluster within families and individuals, leading to the hypothesis of common autoimmunity genes being shared between diseases. This has been confirmed through studies demonstrating association of the HLA region, the CTLA-4 gene and the PTPN22 gene with many disorders including GD and rheumatoid arthritis (RA). We and others have confirmed highly significant association of the R620W SN...

ea0011p911 | Thyroid | ECE2006

Problems of identifying independent non-class II susceptibility loci within the HLA region for Graves’ disease

Simmonds MJ , Heward JM , Franklyn JA , Gough SCL

The HLA class II region, in particular DRB1/DQA1/DQB1, has been consistently associated with Graves’ disease (GD) for over thirty years. Only recently has work within our own group made progress in narrowing down the etiological variant(s) present within DRB1/DQA1/DQB1, by excluding DQB1, and by mapping association at DRB1 to nine amino acid positions present within the peptide binding domain, with position β74 being the most associated. Independ...

ea0019p387 | Thyroid | SFEBES2009

PTPN22 genotype is a determinant of age of onset of Graves’ disease

Karamat MA , Simmonds MJ , Newby PR , Heward JM , Franklyn JA , Gough SC , Brand OJ

PTPN22, encodes lymphoid tyrosine phosphatise (LYP), an important inhibitor of T lymphocyte activation and has been associated with numerous autoimmune diseases including type 1 diabetes, rheumatoid arthritis, and Graves’ disease (GD). Consistent association has been reported between disease and a non-synonymous SNP +1858 C>T (rs2476601) encoding an Arginine to Tryptophan substitution at amino acid 620 of LYP. Our group was the first to show strong evidence of ...

ea0011oc62 | ThyroidOC57 British Thyroid Association Award | ECE2006

The role of the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) in fetal brain development

James SR , McCabe CJ , Smith VE , Chan SY , Barrett TG , Franklyn JA , Kilby MD

Thyroid hormones play a major role in the metabolic function of mammalian cells and are of particular importance in the development of the fetal brain. The MCT8 gene has recently been shown to encode an active and specific thyroid hormone transporter. Recent reports have identified mutations in the MCT8 gene in several unrelated boys presenting with severe X-linked psychomotor retardation and elevated serum T3.Ontogeny of mRNA encoding MCT8 was examined ...

ea0011p330 | Diabetes, metabolism and cardiovascular | ECE2006

How does glucose insulin potassium improve haemodynamic performance? Evidence for beta-adrenoreceptor and sarcoplasmic reticulum calcium ATPase up-regulation

Ranasinghe AM , Quinn DW , McCabe CJ , Pagano D , Franklyn JA , Bonser RS

Objectives: Glucose insulin potassium (GIK) improves haemodynamic performance following coronary artery bypass graft surgery (CABG). We postulated that this might be secondary to beta-1 adrenergic receptor (ADRB1) up-regulation and changes in myocyte calcium handling.Methods: We performed a randomised double-blind placebo-controlled trial on patients undergoing first time elective/urgent on-pump CABG (LREC approval obtained). A cohort of 48 patients rand...

ea0011p487 | Endocrine tumours and neoplasia | ECE2006

PTTG promotes a novel VEGF-KDR-ID3 autocrine mitogenic pathway in thyroid cancer

Kim DS , Buchanan MA , Stratford AL , Susarla R , Watkinson JC , Eggo MC , Franklyn JA , McCabe CJ

VEGF exerts its effects by binding to two tyrosine kinase receptors, KDR and VEGFR1. KDR is critical for transmitting signals for proliferation and migration of endothelial cells but is also expressed in several non-endothelial cells, and is elevated in some human tumour cells. We investigated KDR expression in human thyroid epithelial cells in vitro and thyroid cancers compared with normal thyroid samples examined ex vivo. Expression of KDR was demonstrated usin...

ea0011p561 | Growth and development | ECE2006

RAD21-dependent effects of securin/PTTG and separase on fetal neuronal NT2 cells

Pemberton HN , Boelaert K , Kim DS , Chan SY , Kilby MD , Franklyn JA , McCabe CJ

During the metaphase to anaphase transition of mitosis, destruction of the human securin, pituitary tumor-transforming gene (PTTG), and subsequent activation of the cysteine endopeptidase separase, leads to the cleavage of RAD21, a component protein of the cohesin complex. The developing fetal brain has rapidly proliferating neuronal cells, whilst adult neurons no longer proliferate and are maintained in G0 status of the cell cycle. We have previously investigated the expressi...

ea0011p850 | Thyroid | ECE2006

Association of the FCRL3 gene with Graves’ disease in the UK Caucasian population

Simmonds MJ , Heward JM , Carr-Smith J , Franklyn JA , Gough SCL

Recently, linkage between chromosome 1q23 and rheumatoid arthritis within the Japanese population has been narrowed down to association of four single nucleotide polymorphisms (SNPs), fcrl3_3, fcrl3_4, fcrl3_5 and fcrl3_6, within FCRL3, a known regulator of B cell signalling. Of these four SNPs, fcrl3_3 was shown to disrupt FCRL3 expression on B cells, suggesting a potential etiological role. Association of fcrl3_3 was also replicated in a Japanese Graves’ disease ...