A Pilot Study of Dietary Nitrate Supplementation in Anaemic Patients.

Conference poster presented at Clinical Trials Symposium, RD&E 5/11/15.Anaemia affects 60-90% of people with cancer. A lower haemoglobin (Hb) is associated with a worse quality of life. Erythropoietin treatment improves both Hb and quality of life but is associated with significant risk. Blood transfusions improve Hb but only have a short-term effect on quality of life. Stored blood has a reduced NO bioavailability causing reduced vasodilation, reduced blood flow and oxygen delivery to muscles, and reduced exercise tolerance and muscle oxidative function. Dietary nitrate supplementation has been shown to be of significant benefit in healthy individuals. It improves mitochondrial efficiency, reduces metabolic rate, increases blood flow to areas of the body requiring more oxygen, and reduces the effect of hypoxia on exercise capacity and muscle recovery.Research funded by Exeter Leukaemia Fund, Royal Devon & Exeter NHS Foundation Trust and the University of Exeter

Current Use of Nephelometric Quantification of Serum Free Light Chains (FLCs) in the Management of Plasma Cell Dyscrasias, and the Potential Benefits of Point-Of-Care Testing.

Conference poster displayed at British Society for Haematology Annual Scientific Meeting, Edinburgh, 20-22 April 2015.Quantitative nephelometric assays detecting polyclonal sheep anti-sera and serum FLCs (e.g. Freelite®) are the gold standard method for monitoring FLC secretion from myeloma cells, but are only available in central laboratories. The frequent delay between venepuncture and assay results can affect diagnosis, treatment decisions and patient communication. Second generation point-of-care assays have been developed using monoclonal antibodies to FLCs, producing results in 10 minutes (e.g. Seralite®). This study investigates potential impact on care of patients with plasma cell dyscrasias.Dave Veale funded by Exeter Leukaemia Fund

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Functional characterization of a defense-related class-III chitinase promoter from Lupinus albus, active in legume and monocot tissues

A class-III chitinase promoter was isolated from Lupinus albus. The region 5′ to the coding sequence of the IF3 gene was amplified by gene walking and sequenced. The proximal 2.0 kb sequence contains a predicted promoter site, including a TATA box, near the ATG start site. To test for minimal sequences needed for promoter activity, the region was restricted into fragments of 1.81, 1.51 and 1.13 kb and cloned into the pDM327 vector, upstream from the bar-gus fusion gene for Biolistic™ transformation. Transformation of lupin embryos, bean callus tissue, maize embryos and Ornithogalum callus demonstrated promoter activity for all fragments. In silico analysis identified putative cis-acting elements in the 1.81 kb fragment that could be important in controlling gene expression. Fungal elicitor activated-, woundinducible- and ethylene responsive elements were present in the 1.51 kb fragment. Myb elements and CAAT boxes that regulate responses to environmental factors and modulate promoter efficiency were identified in the 1.81 kb fragment. The 1.51 and 1.81 kb fragments were inserted upstream of the gus gene into the pBI121 vector for Agrobacterium tumefaciens transformation of tobacco. Quantitative GUS assays indicated that the promoter fragments are functional in planta and inducible by defense-related signals, wounding, as well as chemical elicitation. All important elements essential for Bion inducibility are present on the shorter (1.51 kb) promoter fragment, but both 5′ distal and proximal cis-elements are required for full functionality. The IF3 promoter is, thus, suitable for use in defense gene constructs prepared for the production of anthracnose resistant lupin.South African Agricultural Research Council (ARC) and the Protein Research Trust (PRT).http://link.springer.com/journal/106582017-12-31hb2016Plant Scienc