Learn More
Autosomal dominant periodic fever syndromes are characterized by unexplained episodes of fever and severe localized inflammation. In seven affected families, we found six different missense mutations of the 55 kDa tumor necrosis factor receptor (TNFR1), five of which disrupt conserved extracellular disulfide bonds. Soluble plasma TNFR1 levels in patients(More)
The normally functioning immune system is subject to intricate networks of regulatory mechanisms: it is therefore not surprising to find that autoimmune diseases present a complex pathogenic picture in which the relative contributions of various factors probably determine the precise nature and course of disease. This is particularly evident in the effector(More)
We propose a quantitative theory of microscope interferometry where the specimen is illuminated by a cone of monochromatic light of solid angle 0 - 100 degree, corresponding to an illuminating numerical aperture of 0 to approximately 1.2. Computed results compare favorably with photometric measurements of fringe irradiance for a water wedge 0 - 2,000-nm(More)
An introductory clinical trial of the anti-oestrogenic agent IC146474 in late or recurrent carcinoma of the breast is described.Forty-six patients have been treated, of whom 10 have shown a good response. This is of the same order as that seen with oestrogens and androgens.The particular advantage of this drug is the low incidence of troublesome side(More)
OBJECTIVE To investigate the effect of mutations in the tumor necrosis factor receptor superfamily 1A (TNFRSF1A) gene on the conformation and behavior of the TNFRSF1A protein. Mutations in TNFRSF1A cause the autosomal-dominant, autoinflammatory TNFR-associated periodic syndrome (TRAPS). METHODS The expression of recombinant TNFRSF1A was compared in(More)
The generation of an autoimmune response against islet beta-cells is central to the pathogenesis of type 1 diabetes mellitus, and this response is driven by the stimulation of autoreactive lymphocytes by components of the beta-cells themselves. Reactive oxygen species (ROS) have been implicated in the beta-cell destruction which leads to type 1 diabetes and(More)
Autoantibodies to 65 kDa glutamic acid decarboxylase (GAD65) are produced in many patients with autoimmune polyendocrine syndrome type II (APS-II) or stiff-man syndrome (SMS) and are heterogeneous in their epitope specificities, recognizing both conformational and linear determinants. Major linear epitopes of GAD, which are recognized by autoantibodies in a(More)
Tumour necrosis factor (TNF)-receptor-associated periodic syndrome (TRAPS) is a hereditary autoinflammatory disorder involving autosomal-dominant missense mutations in TNF receptor superfamily 1A (TNFRSF1A) ectodomains. To elucidate the molecular effects of TRAPS-related mutations, we transfected HEK-293 cells to produce lines stably expressing high levels(More)
It has been proposed that cytokines play a role in the pathogenesis of chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS). However, different studies have reported conflicting results using enzyme-linked immunosorbent assay or polymerase chain reaction to detect cytokines in these conditions. In the present study, for the first time, the(More)
Multiplex immunoassays confer several advantages over widely adopted singleplex immunoassays including increased efficiency at a reduced expense, greater output per sample volume ratios and higher throughput predicating more resolute, detailed diagnostics and facilitating personalised medicine. Nonetheless, to date, relatively few protein multiplex(More)